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-Ted talk voiced by Toine Heijmans, explaining his father's journey through Alzheimer's.
- Alzheimer's affects everyone differently only thing doctors can promise is that they don't know much.
-once someone is diagnosed with Alzheimer's children are appointed caregivers.
- caregiver represents cruelty and being exhausted can feel like forced labor.
- like being dropped in a jungle with only a flashlight
-people around can help but every person who tries cant truly understand because every situation is different you can find closure in the people around you going through it with you.
-care givers are survivors who give all they have to their loved once and many times feel alone because the parent you once knew now is like a zombie.

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Toine Heijmans: Who cares for the caregivers?

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Alzeimers is different for everybody. No one knows what will haven for any person. They were told his father could change quickly or slowly. 'This talk is not about him; it's not about my mellow dad that turned into an angry man. It's not about my stubborn dad who wanted to be the director of his own life.

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This is a scholarly article presented by the national Library of Medicine. Having a parent with Alzheimer's puts you at a higher risk of developing the disease when you are older. As of now 27 million individuals have it and the number is only going the raise.  This will put more children in the place to care for their parents as well as a raise in mental health disorders.

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Alzheimer Dis Assoc Disord. Author manuscript; available in PMC 2012 Jun 18.

Published in final edited form as:

What Does the Future Hold?

Lissy Jarvik, MD, PhD,*†‡ Asenath LaRue, PhD, § Deborah Blacker, MD, ScD, ‖ Margaret Gatz, PhD, ¶ Claudia Kawas, MD,# John J. McArdle, PhD, ¶ John C. Morris, MD,** James A. Mortimer, PhD, †† John M. Ringman, MD, ‡‡ Linda Ercoli, PhD,*‡ Nelson Freimer, MD,*‡ Izabella Gokhman, MD, §§ Jennifer J. Manly, PhD, ‖‖ Brenda L. Plassman, PhD, ¶¶ Natalie Rasgon, MD, PhD,## Jeffrey Scott Roberts, PhD,*** Trey Sunderland, MD, ††† Gary E. Swan, PhD, ‡‡‡ Phillip A. Wolf, MD, §§§ and Alan B. Zonderman, PhD ‖‖‖

Abstract

Children of persons with Alzheimer disease (AD), as a group, face an increased risk of developing AD. Many of them, throughout their adult lives, seek input on how to reduce their chances of one day suffering their parent's fate. We examine the state of knowledge with respect to risk and protective factors for AD and recommend a research agenda with special emphasis on AD offspring.

Keywords: Alzheimer disease offspring, risk factors

Much has been learned about Alzheimer disease (AD) since Alois Alzheimer first described it more than a century ago,1 but to date no consensus has been reached on its etiology, no universally accepted preventive interventions have become available, and treatments are only minimally effective. Although a considerable amount of research is underway, much of it is as yet inconclusive and often mired in significant methodologic challenges. Meanwhile, the number of persons afflicted with AD has been steadily increasing. For the United States alone, estimates have been as high as 5 million in 2007,2 up from 4 million.3 Others, using different diagnostic criteria, estimated the prevalence of AD at 1.9 million.4,5 The most recent report, the Aging Demographic and Memory Study (ADAMS),6 a supplemental study of the Health and Retirement Study, yielded an estimate of 2.5 million individuals with AD at the age of 60 years and older in the United States in 2002. ADAMS was based on a nationally representative population sample with in-person assessments of 856 individuals between 2001 and 2003. It is the first study to assess individuals from all regions of the United States to estimate prevalence of dementia and, therefore, should account for regional and ethnic differences in prevalence. Whatever their precise numbers, AD patients are expected to increase as the estimated 70 to 80 million baby boomers (with their advancing age and increasingly greater longevity compared with prior more vulnerable to manifesting the disease. For example, by 2050, the number of people with AD in the United States may range from 11 to 16 million.2

Concerning global prevalence, the best estimates available suggest that 24 to 27 million individuals currently have AD and this number is projected to rise to more than 100 million by 2050.7,8 However, the rate of increase over that interval is not expected to be uniform. Differences in life expectancy across regions of the world, differences in survival after diagnosis of dementia, varying diagnostic conventions, and difficulties in ascertainment (especially in residents of rural underdeveloped areas) and differential exposure to risk factors may play a role (eg, low levels of cardiovascular risk found in some developing countries). Some investigators concluded that incidence and prevalence of dementia show relatively little geographical variation once methodologic issues are taken into account, although there may be greater inconsistencies in some types of dementia (eg, AD) than in others.9 Much more information than currently available is clearly needed.

In light of the increasing magnitude of the suffering caused by AD, and considering its economic burden (in the United States more than $148 billion/y in 20072), the search for factors that might increase or lower the risk of manifesting the disease takes on crucial importance. Observational studies have already suggested several factors that might trigger, induce, or accelerate the development of AD; yet, only a few are generally accepted.10,11 Although it may take many years before efforts to prevent or successfully treat AD will come to fruition, even delaying its onset could substantially reduce prevalence and cost.12,13

Further research may be of particular urgency for the population of adult children of persons with AD ("AD offspring") as they themselves advance in age. There are, however, surprisingly few data available on the risks faced specifically by AD offspring.14 Even their overall number, which most likely ranges well into millions, remains as yet unknown. Longitudinal studies ongoing worldwide are expected to yield much needed information. In the United States, for example, studies focusing on AD offspring include, but are not limited to, the Risk Evaluation and Education for Alzheimer's Disease (REVEAL) study,15 the Wisconsin Registry for Alzheimer Prevention (WRAP) study,16 the Washington University Adult Children study,12 and the Framingham Offspring study.17 Results of these investigations will complement what has been learned from longitudinal studies of mixed samples of AD relatives (children and siblings or parents), including the National Institute of Mental Health's Biomarkers in Older Controls At Risk for Dementia (BIOCARD) study,18 studies of persons at risk for AD,19-26 additional family studies of AD,27-31 and twin studies.32

In this article, we will (i) briefly summarize generally accepted information regarding risk and protective factors and (ii) make recommendations for a research agenda designed to assess genetic and nongenetic risks and protective factors with special emphasis on AD offspring. Our purpose is not to supply a comprehensive review of the literature, but to provide enough background to understand the urgent need for further research in AD and the recommendation of strategies for future research.

RISK FACTORS FOR AD

Risk factors for AD are notoriously difficult to isolate as they interact with each other in a variety of ways. As a result, the outcomes of different studies are sometimes hard to reconcile and frequently require further clarification. Moreover, there is no uniform method of reporting (eg, prevalence, incidence, and lifetime risk), further complicating comparison of study outcomes. Nevertheless, 2 risk factors have become firmly established: chronologic age and positive family history.

Chronologic age has emerged as a crucially important risk factor, not only in itself but also, as we will see, through its interactions with a variety of other risk factors. For example, in a recent collaborative study carried out in 8 European countries, the pooled AD incidence rate per 1000 person-years rose from 1.2 to 9.1 and 35.3 for ages 65 to 69, 75 to 79, and 85 to 89 years, respectively.33 In the United States, the current prevalence of AD is estimated as 2%, 19%, and 42% for age groups 65 to 74, 75 to 84, and 85+ years, respectively.2

Positive family history of AD is another risk factor for AD, independent of any identified genetic factors. It is generally reported that a person with at least 1 first-degree relative with dementia has 2 to 4 times the lifetime risk of developing AD compared with someone without such a relative.28 These estimates may be sensitive to age structure and other modeling issues, such as the uncertainty of the diagnosis of AD/dementia in long-deceased relatives, and conversely, the inability to classify relatives who did not live through the age of risk as clearly free of AD/dementia. Moreover, although positive family history increases the risk for developing AD, this effect may diminish with age and may be minimal or absent after the age of 85 years.31 Other studies point to a different interaction effect of chronologic age and positive family history. The age at which the first-degree relative with AD (proband) manifests the symptoms of AD [age at onset (AAO)] may itself be a risk factor for the development of AD. The younger the proband's AAO, the greater the genetic risk for the relatives, regardless of the age of the relatives themselves.34,35

Within the group of first-degree relatives, the highest risk is faced by persons who have an identical twin with AD. The study of twins (identical or monozygotic and fraternal or dizygotic) offers a unique opportunity to explore the relative contributions of genetic and other influences to the risk of developing AD. In the largest twin study to date, the Swedish twin study,32 heritability of AD was estimated to be 58%, with nongenetic risk factors playing an important role (nonshared environmental influences 23%, shared environmental influences 19%). In addition, twin studies clearly document that even in concordant twins (ie, both twins develop AD) there can be differences in AAO of as much as 16 years, indicating that the effects of both chronologic age and positive family history vary significantly as they interact with other risk factors.

Genetic Risk Factors

AD provides one of the best examples of the importance of distinguishing between 2 types of genetic variants that contribute to the risk of developing a disease: (i) Highly penetrant variants are usually rare, inherited in a simple (Mendelian) pattern, and provide remarkable insight into the basic biologic process underlying the disease. (ii) Less penetrant variants display complex segregation patterns and, therefore, may be less informative than Mendelian variants with respect to elucidation of pathobiology. However, they are often common, which increases the likelihood that they will substantially enhance our understanding of disease risk at the population level.36 More than 100 genes have been implicated in the development of AD through genetic association studies (see AlzGene, www.alzgene.org 37) and other studies,38-43 but only 4 genes have so far been clearly established as contributing to the development of the disease: the 3 so-called "Alzheimer genes" [Amyloid Precursor Protein ( APP), Presenilin 1 (PS1), and Presenilin 2 (PS2)] and the susceptibility gene APOEe4. The 3 Alzheimer genes all display rare but highly penetrant autosomal dominant mutations that lead to early-onset AD. In the 1980s, the study of the Alzheimer plaques, consisting largely of β-amyloid protein (Aβ), focused interest on Aβ44 and led to the discovery that alterations in APP on chromosome 21 are a cause of some cases of familial AD.45 PS1 46 and PS2 47 were subsequently discovered by linkage to other families with AD. The pathogenic mutations in all 3 of these genes were found to have the common effect of causing aberrant processing of APP to produce elevated levels of Aβ ₄₂,48 the more fibrillogenic form of Aβ thought to be the most critical in causing the amyloid pathology. Further evidence for this "amyloid hypothesis" came from the study of Down syndrome with essentially all persons living into their sixth decade of life developing AD neuropathology and some progressive cognitive and behavioral deterioration.49 The amyloid hypothesis unifies a number of diverse observations, contributes substantially to our understanding of the pathobiology of AD, and has opened up promising therapeutic avenues even though overproduction of Aβ ₄₂ does not by itself explain all aspects of AD pathology.52 However, the Alzheimer genes are so rare that all 3 account for <1% of AD.51

By contrast, the ε4 allele of the gene encoding apolipoprotein E ( APOE ε4) has been established as the most important genetic risk variant in population samples of all ages. APOE ε4 is common but only modestly penetrant, and it remains unclear at a biologic level as to how it contributes to the development of AD. Diverse animal experiments have suggested that the risk of APOE ε4 for AD may be mediated through either amyloid-dependent53 or amyloid-independent54 pathways. We expect that multiple additional AD susceptibility genes (most likely relatively low penetrance variants) and nongenetic risk factors will be discovered that contribute to AD risk. Fortunately, the technology is now available to identify such variants through well-powered genome-wide association (GWA) studies. The International HapMap Project55 has identified several million single nucleotide polymorphisms (SNPs) that can be used (employing currently available commercial assays) to conduct GWA studies in samples drawn from diverse ethnic populations. Some GWA studies of AD are now underway. The cost is relatively low even for samples of several thousand individuals.

APOE ε4, the only confirmed susceptibility gene for AD, has been found in over 100 studies to increase vulnerability to AD at all ages. In the United States, about one-half to two-thirds of persons with late-onset AD carry the APOE ε4 allele.56-58 The frequency varies with age and findings vary as to the magnitude of risk conferred by APOE status.59 A recent analysis of European Americans60 determined that ε4 homozygotes occurred significantly more often among individuals with early-onset AD (20.3%) than among late-onset AD (8.2%) confirming the findings from previous studies. It has been known for a decade61 that the APOE ε4 effect is evident at all ages between 40 and 90 years, but diminishes after the age of 70 years. For heterozygous APOE ε4 carriers, compared with noncarriers, the increased lifetime risk of developing AD has been estimated as 3-fold to 4-fold, and for homozygotes as 2-fold to 10-fold or 15-fold. In population studies, the percentage of persons with AD carrying 1 or 2 APOE ε4 alleles ranges from approximately 50% to 70%.56 Risk estimates for dementia in the general population range from 25% to 50%, and studies of APOE ε4 homozygotes found a dementia prevalence of 50%62 or less.57,61

Global variation in APOE ε4 allelic frequency could contribute to different rates of AD among populations with European, Asian, and African ancestry. In European populations, prevalence estimates for the APOE ε4 allele range from 7.3% (Poles) to 19.8% (Norwegian); the range is somewhat more restricted in Asia/East Asia, extending from 0.0% (Koch) to 17.0% (Javanese), and wider in Africa, where prevalence estimates range from 3.0% (Senegal) to 40.7% (Biaka). Allele frequencies are available at http://alfred.med.yale.edu. An extensive review of ethnic differences63 concludes that despite differences in sampling methods, definitions of dementia, and definitions of race/ethnicity as well as discrepancies in functional and neuropsychologic assessments, there are ethnic differences in the observed prevalence and incidence of cognitive impairment, dementia, and AD. Although AD has been found in all ethnic groups that have been examined, data are relatively scarce, and arguably might be more indicative of the challenges of culturally fair measurement than of decreased cognitive functioning in the test subjects.64-66 For example, despite its relatively low frequency in China (8.1%), the APOE ε4 allele remains an important risk factor for AD.67 Indeed, according to more recent epidemiologic studies, the rate of AD in China may be similar to that in western populations.68 It is possible also that APOE ε4 may not function as a risk factor across all populations such as in Chinese of Guangzhou69 and Nigerians of Ibadan.70 In African Americans too, several studies show little to no increase in the risk of AD with the APOE ε4 allele, whereas others did find an association between APOE ε4 and AD.74-76 The Wadi-Ara Arabs in northern Israel constitute another population of interest, given their unusually low ε4 allele frequency despite high rates of AD.77 According to 1 report,78 lower serum cholesterol was related to reduced risk of AD only in those who carried no ε4 alleles. Overall, the global data currently available do not support definitive conclusions regarding APOE ε4 and AD (small sample sizes and widely differing methods across studies may be among the most important reasons). Nonetheless, APOE has been considered a good "anthropogenetic and clinical diagnostic marker."79

It is important to remain aware of the fact that not all carriers of the ε4 allele develop AD, even if they live to advanced old age, and many without ε4 do manifest the disease.57,61,62,80-83 A variety of interacting risk and protective factors (as discussed below) has been implicated, but the mechanisms of these interactions are as yet to be explored. Meanwhile, the value of APOE in the diagnosis of AD remains to be established. APOE status has explicitly not been recommended for prediction by multiple national panels84 (see http://www.acmg.net/resources.policies/pol-001.asp for the American College of Medical Genetics consensus statement recommending against routine genotyping of APOE).

Prominent among ongoing research exploring APOE-related issues is the multicenter REVEAL study,15 aimed at understanding the impact of APOE testing. Careful estimates of the relation between APOE, positive family history, and disease risk, prepared for this study85 suggest that the risk was highest for persons with 1 or more APOE ε4 alleles and a first-degree relative with AD. As mentioned earlier, however, the effect of positive family history varies with age until a maximum age after which it may no longer make a significant difference. APOE status may interact with chronologic age in a similar pattern: A recent update on dementia51 confirmed earlier reports61,86 that the APOE ε4 effect is strongest before the age of 75 years. Among findings supporting this conclusion are those of the Cache County study,87,88 which indicate that the age-specific prevalence of AD reaches a maximum and then declines. The maximum was reached at the average ages of 73 and 87 years in APOE ε4 homozygotes and heterozygotes, respectively, whereas the comparable age in participants without ε4 alleles was 95 years. It has, therefore, been suggested that the strongest influence of APOE ε4 may be in accelerating the AAO of AD, and thereby, also lowering the age of maximum risk.87

In a similar vein, it has been proposed that APOE ε4 may be an indicator of a general frailty factor that may lead to death before the AAO of AD.89,90 At the same time, this general frailty factor may increase vulnerability to AD in those who live long enough to manifest the disease. APOE ε4 has also been implicated in the excess mortality associated with AD, but again, the mechanisms behind this risk have as yet not been identified.91 Methodologic issues have hampered research in this area and further investigations will require sophisticated methodology such as multistage survival models.

APP, PS1, PS2, and APOE ε4 overall account but for a small amount of the genetic component of the risk of AD. Additional unidentified genes are clearly in operation. As mentioned before, over 100 genes have already been implicated but have not as yet been confirmed. One recent example is the proposed linkage of AD risk to variants in the intronic region of the SORL1 neuronal sorting receptor.92 These variants may regulate the expression of SORL1 that is involved in directing the intracellular trafficking of APP. Differences in SORL1 expression levels could lead to quantitative differences in the pathways through which APP is processed. A second example comes from a recent genome-wide survey reporting that polymorphisms in the gene encoding for growth factor receptor-bound-associated binding protein-2 (GAB2) were associated with an increased risk of AD among persons carrying the APOE ε4 allele.93

Other Risk Factors

In addition to age, positive family history, the 3 Alzheimer genes, and APOE ε4, other potential risk factors such as head trauma, cardiovascular disease, hypertension, diabetes, and atherosclerosis have been suggested.12 Sex (even after accounting for survival differences) may interact with APOE ε4 to influence cognitive decline and, so may educational attainment and brain reserve.95,96 The association between smoking and the development of dementia is unclear. Although animal experiments generally show a detrimental effect,97 results of epidemiologic studies have varied, the more recent ones tending to show an increased risk for dementia in long-term smokers.98

There has also been support from epidemiologic studies for the protective effect of nutrition and dietary supplements.99,100 Reportedly, certain fish,101 n-3 fatty acids,101 antioxidant supplements,102-104 homocysteine, 105 and reduction of intake of saturated and trans-unsaturated fat106 may provide protection against AD. There is some evidence that these dietary factors may interact with the APOE ε4 allele, but not in a consistent fashion.107 In addition to, and possibly interacting with diet, exercise has been suggested as a potential protective factor. An emerging body of literature supports that suggestion, concluding that physical exercise may protect against dementia.108 Some of the positive effects of exercise likely reflect its effect on preserving cardiovascular health. Additionally, exercise has been shown to lead to increases in brain-derived neurotrophic factor (BDNF) that would promote brain plasticity.109

Other research has suggested that cognitively stimulating activity in mid-life and late-life may delay or prevent AD.110-112 Finally, there is some evidence that occupations with higher cognitive demands may protect against manifestation of AD.113,114 Notably, studies of leisure activities and occupation are observational and can suffer from reverse causation and third-variable problems that cannot be entirely answered by adding covariates to the analyses. Nonetheless, nutrition and daily activities are to a certain extent under an individual's control. In this sense, they are potentially modifiable by the individual and thus have appeal as targets for interventions.

Depression has long been associated with AD (as a precursor, prodrome, and symptom); yet, the links between them remain to be clarified. Nearly a decade ago, a relationship was reported between insulin levels and severity of AD and APOE genotype,115 and more recently, a hypothesis proposed that insulin resistance (IR) may link AD and depression.116 Epidemiologic evidence supports an association between insulin dysregulation, cognitive decline, and AD.117 Although the exact mechanism of action of IR in the central nervous system is not known, it is thought that IR may lead to inadequate brain glucose metabolism. Glucose dysregulation clearly seems to increase the risk of AD even after exclusion of cardiovascular risk factors118; moreover, an association between IR-related vascular disorders and AD has been documented.119 It has also been pointed out that IR may develop as a consequence of weight gain and obesity associated with the neurovegetative symptoms of depression and some of the common pharmacologic treatments for depressive disorders such as use of atypical antipsychotics and anticonvulsants.120

Diabetes has been reported to increase risk for cognitive decline and AD. Potential mechanisms for an association between diabetes and AD are (a) through cerebrovascular disease,127 (b) through increased oxidative stress,128 (c) through generation of advanced glycosylated end products,129 and (d) through insulin.130 The Washington Heights/Hamilton Heights/Inwood Columbia Aging Project (WHICAP)131 and Rotterdam124 studies reported an increased association between diabetes and AD in subjects treated with insulin and a large proportion of diabetes in the elderly may be explained by IR.128

In addition to the likelihood that the IR-depression-AD association will help to identify biologic mechanisms in the development of AD, it has potential clinical usefulness. Early identification of a subgroup of patients with depressive disorders and IR, with or without additional risk factors for AD, could lead to appropriate changes in medication regimens, preventive measures targeting AD, earlier diagnosis, and intervention.

Observational data have suggested an association between hyperlipidemia and AD,132,133 and also an association between use of lipid-lowering medications,134 and a decreased risk of AD. In an observational study of 1037 postmenopausal women with coronary heart disease enrolled in the Heart and Estrogen/Progestin Replacement Study, women in the highest low-density lipoprotein (LDL) cholesterol quartile at cognitive testing had low Modified Mini-Mental State Examination scores and an increased likelihood of cognitive impairment.135 However, other studies136,137 failed to find the association.

Risks Faced by AD Offspring

We have not been able to find specific risk estimates for AD offspring in our survey of the literature.14 One of the few studies focusing on AD offspring is the previously cited and ongoing multisite REVEAL study. In a series of randomized clinical trials of the predictive use of APOE testing, AD offspring and siblings have been provided risk information that incorporates APOE test results, and the psychologic and behavioral impact of this risk information on participants has been assessed up to 1 year after disclosure.15 Results to date suggest that genetic risk information for AD, when delivered in a controlled research context by trained professionals, does not generally result in adverse psychologic effects among recipients. The study uses risk curves to clarify to participants the meaning of their APOE results.85 In the absence of data specific for AD offspring, the risk curve estimates are based on family history data from other populations, such as the multicenter Multi-Institutional Research in Alzheimer's Genetic Epidemiology (MIRAGE) study of nearly 13,000 siblings and parents of AD patients and a 50-study pooled analysis of APOE-AD association in general populations. At this stage, like many other studies, REVEAL has no choice but to combine the risks for different types of first-degree relatives. However, discrepancies in frequencies obtained for parental as compared to sibling dementia, suggest that although it may be appropriate to use combined risk estimates for first-degree relatives when estimating purely genetic risks for developing AD, it may be suboptimal to do so when estimating the overall risk faced by AD offspring.

Today, AD offspring have unprecedented opportunities to apply potentially protective measures against AD. The recent decrease in heart disease and stroke, which may lead to a potential reduction in risk for AD, may be attributable at least in part to the availability of such new information. Putative protective measures against AD include improved diet and lifestyle, increased exercise, mental stimulation, social interaction, and the consumption of vitamins, nutraceuticals, and over-the-counter as well as prescription drugs (such as hormones, statins, and anti-inflammatory agents). Moreover, educational attainment, which seems to decrease risk of AD, has increased markedly over the last 2 generations. However, there are also risk factors that are on the rise. For example, the emerging epidemic of obesity may lead to increased risk of AD138 and the consequences of the widespread substance abuse, beginning in the 1960s, remain unknown.

The genetic risk to AD offspring may thus be strongly modified by nongenetic factors that influence the timing of onset and ultimate expression of AD. Whether a factor will affect risk for AD may depend on the timing and duration of the exposure before onset of clinical symptoms. Because individuals genetically vulnerable to AD may not react in the same way as the general population in whom the risk and protective factors were identified, studies of risk and protective factors specifically within groups of AD offspring are urgently needed. In this context, it is important to point out that most of what is known about nongenetic risk and protective factors for AD has been obtained from studies in which the family history of participants is either unknown or poorly documented. As a result, potential interactions of familial status with other risk and protective factors have not been adequately examined.

In contrast to the general lack of data on protective factors in AD offspring, 2 prevention trials targeted first-degree relatives of AD patients: the Alzheimer's Disease Anti-inflammatory Prevention Trial (ADAPT) and the Preventing Postmenopausal memory loss and Alzheimer's with Replacement Estrogens (PREPARE) trial (see http://clinicaltrials.gov for study descriptions). An early report failed to detect significant differences in the ADAPT study.139 Unfortunately, both trials were discontinued prematurely owing to concerns about drug safety (celecoxib and estrogen, respectively).

EARLY MARKERS

While awaiting clarification of interacting risk and protective factors, efforts are underway to identify markers that would be useful for early diagnosis of AD and for charting disease progression or regression in relation to therapeutic interventions. It is generally assumed that the earlier the detection, the greater the likelihood of arresting or reversing the course of AD. Optimally, AD markers would detect the disease early enough to prevent its manifestations. That goal is not as yet within reach, but ongoing research offers hope of achieving it. Below, we group the potential early markers currently being explored under the following 3 headings: cognitive performance, neuroimaging, and other potential early markers.

Cognitive Performance

Mild performance deficits on cognitive tests have been linked to increased risk of dementia in several short-term longitudinal studies of elderly samples.140-148 These relationships have fueled attempts to define and characterize preclinical syndromes such as "mild cognitive impairment" (MCI) or "cognitive impairment, no dementia" (CIND) that may be useful for research with elderly samples.149,150 There are disagreements among researchers as to how best to interpret such cognitive deficits. Some consider MCI a prodrome of AD or other forms of dementia,151 whereas others point to the variable course and instability of psychometrically defined mild cognitive impairment.152

Only a few prospective studies have addressed the question of long-term predictive utility of cognitive tests. These studies have shown statistically significant associations between subclinical cognitive deficits or low levels of cognitive performance and increased risk of dementia across time spans as long as 10 to 20 years.153-156 In these studies, baseline cognitive differences are very mild indeed, with mean scores of persons who eventually develop AD often falling in the low-average range. A related investigation, the well known "Nun Study," documented an association between relatively low-idea density in samples of writing produced at an average age of 22 years and the diagnosis of dementia nearly 6 decades later.157 None of these studies reported results for AD offspring as a distinct at risk group.

Table 1 lists longitudinal studies with neuropsychologic data on samples known to include AD offspring. The table is limited to US studies in which longitudinal cognitive data were already reported or are in the process of being collected, and it excludes studies that focused exclusively on relatives of patients with early-onset disease.164,165 Representative publications are listed, but citations do not include all publications from a given study. To our knowledge, only 2 relatively small studies158,159 reported longitudinal cognitive data for first-degree AD relatives and comparable controls without a family history of dementia; both are limited by their use of mixed offspring and sibling samples and retest intervals of only a few years. Additional studies of AD offspring are currently underway.

TABLE 1

Sample

Design/Procedures

Results/Comments

UCLA/West LA VA Family Study of Alzheimer Disease19,158

Family Studies of Alzheimer Disease (UCLA)159,160

U. Arizona/Mayo-Scottsdale24,161

NIMH BIOCARD Study18,162,163

Several of the investigations summarized in Table 1 provide suggestive evidence that subclinical cognitive differences may be detectable by middle age. However, the relationship of these differences to clinical dementia remains to be clarified, as does the extent to which family history may affect predictive associations. To date, except for 1 small long-term follow-up,19 longitudinal findings specific to children of AD parents have not been reported, and methods used to determine family history have often not been described. Direct documentation of AD in a parent by autopsy or research level clinical diagnosis is likely to yield a more accurate estimate of the increased risk of disease in offspring than family history interviews alone, particularly for a condition such as AD that may be easily confused with other dementing disorders.166

If reliable associations can be established between mid-life cognition and later dementia risk, several possible interpretations will need to be considered. Subtle mid-life difficulties with memory or attention could reflect relatively stable cognitive phenotypes that may persist with little change unless the individual begins to develop AD or other dementia. Alternatively, mild cognitive problems may correlate with underlying AD brain pathology (known to be present in mild extent for some individuals by early adulthood and to an increasing extent by age 50 and older), and may, therefore, reflect a true, albeit early, dementia prodrome.96 For a discussion of cognitive prodrome vs. phenotype hypotheses, see Greenwood et al18 and Sliwinski et al.167

Mid-life cognitive differences may also covary with health or environmental factors, which in themselves may be risk factors for AD. Clearly, there is a danger of including individuals with preclinical dementia as "normal controls".167 Only long-term prospective studies can clarify the meaning of mid-life cognitive differences, but in the near term, studies that relate cognitive performance to functional neuroimaging or other potential biomarkers are a high priority.

Neuroimaging

Functional neuroimaging methods are among the most promising approaches currently available for identifying possible early AD changes. Although these technologies are relatively new and continue to develop,171 several research groups reported reduced rates of cerebral glucose metabolism (in brain regions known to be affected in AD) among clinically normal middle-aged and younger adults with 1 or more APOE ε4 alleles. Differentiating patterns have also been documented with functional magnetic resonance imaging (fMRI) for APOE ε4 carriers and noncarriers.23,173 Added to this are the findings from MRI volumetric studies that show smaller hippocampal size174,175 and greater longitudinal decline in hippocampal volume for APOE ε4 carriers compared with controls.176 It has recently been suggested that PIB (Pittsburgh Compound-B) amyloid imaging may be sensitive for detection of a preclinical AD state.177,178 One patient came to autopsy 3 months after the PIB scan and the autopsy report confirmed the detection of β-amyloid by PIB.179 According to the results of another study,180 2-(1-{6-[(2-[F-18]fluoroethyl)(methyl)amino]-2-naphthyl}ethylidene)malononitrile-PET (FDDNP) binding may be able to determine regional cerebral patterns of plaques and tangles and potentially distinguish persons with MCI or AD from normal controls. For these and other potential markers, longitudinal followup will be needed to determine how closely outcomes are linked to eventual development of AD.

For the study of AD offspring, 3 recent investigations provide particularly intriguing results. Strong family history effects, independent of APOE ε4 genotype, were observed in fMRI activation patterns among asymptomatic children of autopsy-confirmed AD patients26 and in a second, independent sample of AD offspring where parental disease status was determined by autopsy, clinical assessment, or medical record review.181 A third group reported distinctive fMRI findings for cognitively normal middle-aged adults with both an APOE ε4 allele and a family history of dementia, compared with persons with neither risk factor.182 Specific findings have varied with different samples and study procedures. Considered together, however, these recent results suggest that failure to account for family history of AD in research samples may obscure potentially significant clues in the search for early markers of AD.

Other Potential Early Markers

Other potential markers of early AD include total tau in cerebrospinal fluid (CSF), phosphorylated forms of tau in CSF and plasma and also CSF β-amyloid, oligomeric forms of β-amyloid, and isoprostanes.183 In addition to candidate biomarkers, current proteomic and metabolomic technologies hold promise in the identification of formerly unknown biochemical markers of AD.184,185 There are many more potential biomarkers for AD and some of these have already been investigated in a preliminary fashion such as plasma homocysteine,186 CSF sulfatide,187 α-1-antichymotrpysin,188 and the ratio of APP isoforms in platelets.189 However, because of the nonspecificity of some of the markers and the variability of others, only CSF markers of tau and β-amyloid have generated sufficient interest and scientific data to be considered viable biomarkers at this stage of development.190 There is evidence that these CSF measures can be 80% to 90% accurate in establishing the diagnosis of AD versus controls.191-193 Given that this rate is similar to what has previously been set as the autopsy standard,194-198 this is remarkable progress for a test that is available during life when diagnostic issues are critically important to patients' treatment. However, to establish the predictive value of these and other potential biomarkers, they will have to be studied prospectively over extended periods of time in AD offspring. For example, although detection of PIB binding using nuclear imaging seems to be an indicator of the presence of amyloid pathology, the implications of PIB binding remain undefined for the future development of AD in asymptomatic persons.

Promising research currently underway in this area includes the NIMH's BIOCARD study,162 the WRAP study,16 the Washington University Adult Children study,12 and studies of persons at risk for familial AD. As these studies are in their early stages, long-term follow-up data are lacking. Prospective studies of AD offspring over extended periods of time are needed to determine the usefulness of these and other markers not only in early detection of AD but also in prediction of response to treatment and preventive interventions. Combining several possible preclinical markers (eg, amyloid imaging and CSF biomarkers177 or risk factors199) to form risk profiles may be an especially powerful method for advancing predictive accuracy.

It is important to bear in mind that many (if not most) of the studies examining the biomarkers mentioned in this section on "Other Potential Early Markers" are restricted to "clean" subjects, that is individuals who are relatively healthy, without a history of head trauma and free from numerous specified medical comorbidities and medications. It is not clear how these selection criteria affected the results and to what extent the findings are applicable to general populations.

RESEARCH RECOMMENDATION

The brief survey provided above leads the authors to make the following recommendation together with 4 implementation strategies:

Devise strategies for assessing genetic and nongenetic risk and protective factors for the development of AD in children of AD parents. Whenever possible, use existing resources to achieve that goal in a cost-efficient and expeditious manner. In particular, utilization of data from prospective studies initiated 40 or more years ago may provide answers to some vital questions within years rather than decades. All strategies will require awareness of methodologic issues and collaboration among researchers at multiple sites to achieve adequate and representative samples. While doing so, consider children of AD parents, together with appropriate controls, as a potentially critical group to recruit for future prevention and intervention studies, especially those doubly at risk by virtue of family history of the disease and specific genotype (eg, APOE ε4).

Strategy 1: Use and build on available population studies and data resources, international and national. Organize data sharing with due consideration to ethical and legal guidelines. Where it is possible to take advantage of existing data archives, results may be achievable within years rather than decades.

1. Build and maintain a comprehensive inventory of research projects currently studying risk and protective factors in samples that are known to include children of AD parents; identify adult children of AD parents within the samples of existing life course studies that have stockpiled appropriate data and have well-characterized AD in the parent sample; and encourage recruitment of adult children from other studies with well-defined populations that presently may not have a longitudinal design or a specific focus on dementia.

2. Include siblings and twins in addition to children of AD patients, to assess more thoroughly the effects of family history of AD on the development of AD. Accounting for generational differences and differences in years of vulnerability experienced by siblings as compared with children raises methodologic issues which need to be addressed. For comparative purposes, include children and siblings of parents without AD and without a family history of AD. Include longitudinal data on all participants and their relatives. Be sure to gather information on age or age at death for unaffected family members to fully characterize their status. For some analyses, it will be necessary to develop a repository of data to be used at a future time. For example, to compare risks associated with different first-degree relatives might require all probands and all first-degree relatives to be assessed at comparable ages.

3. Foster diversity in study populations, building on existing resources [eg, Sacramento Area Longitudinal Study on Aging (SALSA), WHICAP, Chicago Health and Aging Study, Indianapolis-Ibadan Study, ADAMS, the Alzheimer's Disease Research Centers (ADRCs) and Alzheimer's Disease Core Centers (ADCCs)].

4. Form a working group to review research design options and prioritize those research approaches that can evaluate the importance of family history in AD risk, within budget, time, and policy constraints, while controlling for other risk factors.

Strategy 2: Identify a common core of assessment procedures useful for the study of risk and protective factors, keeping instruments as brief as possible, whereas maintaining awareness of, and adapting to scientific advances whenever indicated.

1. Develop consensus regarding criteria for confirming AD in participants' parents. To maximize the yield from existing data, it may be useful for researchers to rank the likelihood that a study participant has a parent with AD on the basis of a continuum of certainty ranging from autopsy confirmation through research level clinical evaluation, review of existing medical records, and questionnaire or interview. Although each of these methods may yield useful information, prospectively documenting AD in a parent, using contemporary criteria, promises to more accurately reflect disease state than obtaining a family history based only on recall of events that occurred years, if not decades, earlier.

2. Develop consensus regarding criteria for selecting controls to compare with children of AD parents. A ranking of likelihood that a study participant's parents did not have AD or other dementia may also be useful, as the apparent absence of AD is highly linked to longevity and may be subject to other detection biases. Ideally, the controls selected will have had both parents live for at least as long as the parents of the at risk offspring. Having access to current diagnoses, or autopsy diagnoses, would clearly improve ascertainment of controls.

3. Develop consensus regarding standardized collection of a common core of information on family history of dementia, race, ethnicity, and ancestry, and current and past lifestyle information (eg, medical, psychiatric, diet, medications, supplements, toxic exposures, mental and social stimulation, exercise, education, and occupation), on the basis of comprehensive review of existing questionnaires and interview methods.

Strategy 3: Explore the usefulness of preclinical changes in biologic measures, especially cognitive and neuroimaging, as early markers of AD.

1. Develop consensus regarding a common core of cognitive assessment instruments (or categories of instruments) useful for the study of preclinical change (eg, measures of memory and executive function, indices of literacy, quality and amount of education), that may be needed to adequately interpret results. Consideration should be given to identifying a small core of standardized tests that could be used across different studies and would be appropriate for ethnically and linguistically diverse populations. This core battery would be similar in principle to the Uniform Data Set200 neuropsychologic battery of the ADRC and ADCC protocols, but should include measures that are sufficiently challenging to detect small performance differences in higher functioning at risk samples. Incorporation of a small number of experimental measures to increase sensitivity to subtle preclinical changes should also be considered.

2. Develop consensus regarding a common core of functional neuroimaging measures. Long-term longitudinal data on neuroimaging changes are lacking because some neuroimaging technologies have only recently been developed. It is important to determine what type of neuroimaging information exists in current databases and to incorporate neuroimaging measures into existing and new longitudinal studies of adult children of AD parents.

3. Develop consensus regarding the inclusion of a common core of biologic samples (eg, DNA, plasma, serum, urine, CSF, and lymphoblastoid cell lines) of highest priority for the study of AD offspring, specifying the goals of each type of sample. In the interest of efficiency and cost effectiveness, and keeping demands on research participants within reasonable limits, investigators will have to agree on a relatively small number of samples.

Strategy 4: Use all available analytic methods to address potential interactions between genetic and other risk and protective factors201.

1. Encourage joint analysis of data from separate studies, including international and national resources.

2. Develop consensus on risk profiles, using information from multiple domains. In constructing such profiles, pay attention to parental AAO of AD and to the timing of exposure to putative risk and protective factors within the life courses.

3. Encourage testing of varying theoretical models of change, taking into account issues of temporal and longitudinal design.

CONCLUSIONS

Millions of children whose parents developed AD spend much of their adult lives wondering whether their future will include a fate like that endured by their parents. Despite the plethora of carefully conducted research studies, we still cannot predict with a satisfactory degree of certainty as to who among them will fall victim to the dreaded disease, nor even how many of them will eventually become afflicted. We do know that the risk of dementia increases exponentially with age. Most other suggested risk and protective factors still lack the robust data required for devising effective preventive and treatment interventions. Early markers to reliably identify vulnerable individuals are urgently needed. At risk individuals may benefit from current trials ( www.alz.org) of potentially disease-modifying interventions. These trials depend on the voluntary participation of families with AD.

Although cross-sectional studies may be useful to determine if a given marker varies with genetic and/or other risk factors, prospective longitudinal investigations are needed to address the predictive value of putative AD markers and the time course to symptom expression. A handful of such studies are now underway, and given the age structure of the samples being studied, they may begin to provide a preliminary picture of risks to AD children within the next decade. If investigators involved in other ongoing longitudinal studies were to determine which of their participants are (or are not) offspring of parents with AD, this could greatly enlarge the pool of subjects and help to fast-track answers to at least some of the questions we identified. However, collaborative prospective, longitudinal studies achieving sufficiently large sample sizes, and using appropriate methodologies will allow us to take another step forward, that is to explore the complex interactions between individual vulnerabilities (genetic and nongenetic) and specific environmental variables. It is important to emphasize that, because of genetic-environmental interactions, the risk and protective factors identified within the general population may not apply to people with a family history of AD, or may operate in a different way. In view of mounting evidence of mid-life168 and even earlier157,169,170 risk factors for dementia, it will be important for some prospective studies to focus on these younger phases of life.

Clearly, further studies with AD offspring are bound to yield valuable insights. Because of the scientific discoveries of the past decades, the methodologies have become available. Now is the time to take advantage of them. For this reason, it is vitally important for children of AD parents to volunteer for research. It is precisely because of our lack of knowledge about risk and protective factors specific to this population that their help as research participants is potentially invaluable. While awaiting results of ongoing research, we urge the children of persons with AD to practice the lifestyle habits that promote good overall health and might perhaps reduce the risk of manifesting AD. We urge our colleagues to participate in initiating the much needed research outlined above.

ACKNOWLEDGMENTS

This paper was inspired by the Workshop "Children of Alzheimer Parent-What Are the Risks?" held in San Diego, CA, March 6th and 7th, 2005. Elvira Jimenez, MPH, provided invaluable assistance to the conference and this manuscript and especially its bibliographic aspects. The critical acumen and editing skills of Petra Hammerl-Mistry, MA, helped shape this manuscript at various stages of its development. The authors gratefully acknowledge their contributions.

Financial support was received from the Albert Parvin Foundation and the Lon V. Smith Foundation to the UCLA/WLAVA Family Study of Alzheimer Disease (L.J.); NIA grant to ADRC 5 P50 AGO5134 (D.B.); NIA grant R01 AG08724 to the Study of Dementia in Swedish Twins (M.G.); NIA grant P50 AG16573 to ADRC (C.K.); NIA grant P01 AG026276 to the Washington University Adult Children Study (J.C.M.); NIA K08AG-22228 and P01 AG-1657 (J.M.R.); the Larry L. Hillblom Foundation and Turken Foundation (L.E.); NIA grant AG08549 to the Duke Twins Study of Memory in Aging (B.L.P.); NHGRI/NIA grant R01 HG/AG 02213 to the REVEAL Study (J.S.R.); NHLBI grant HL51429 and NIA grant AG09341 (G.E.S.); and NIA grants 5R01 AG08122 to the Epidemiology of Dementia in the Framingham Study and 5R01 AG16495 to the MRI, Genetic, and Cognitive Precursors of AD and Dementia Study (P.A.W.); and the NIA Intramural Research Program of the NIH contributed to the support of this research (A.B.Z.).

REFERENCES

1. Alzheimer A. Uber eine eigenartige Erkrankung der Hirnrinde. Allgemeine Zeitschrift fur Psychiatrie und Psychiatrisch-Gerichtliche Medizin. 1907;64:146-148. reprinted with translation by L. Jarvik and H. Greenson. About a peculiar disease of the cerebral cortex. [ Alzheimer Dis Assoc Disord. 1987; 13-18. Google Scholar]

58. National Institute on Aging. Rockville, MD: National Institutes of Health; 1995. Progress Report on AD. [ Google Scholar]

142. Bondi MW, Monsch AU, Galasko D, et al. Preclinical cognitive markers of dementia of the Alzheimer type. Neuropsychology. 1994;8:374-384. [ Google Scholar]

155. La Rue A, Jarvik LF. Reflections of biological changes in the psychological performance of the aged. Age. 1980;3:29-32. [ Google Scholar]

198. Jarvik LF, Matsuyama SS, Chui H, et al. Autopsy diagnoses of Alzheimer disease: independent reviews and clinical implications. Int J Geriatr Psychiatry. 1995;10:505-510. [ Google Scholar]

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Children of Persons With Alzheimer Disease: What Does the Future Hold?

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Children of persons with Alzheimer disease (AD), as a group, face an increased risk of developing AD. Many of them, throughout their adult lives, seek input on how to reduce their chances of one day suffering their parent's fate. We examine the ...

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This is a blog from the Joan's Family Bill of Rights talking about children dealing with Alzheimer's. “'Ambiguous loss' is a term used to describe the loss that an adult child may feel when the parent is physically present but may not be mentally or emotionally connected." This type of grief is very different it is not sudden you sometimes have years to grieve. It is hard to understand that you are also grieving because the person you are grieving is still alive. Children caregivers also face a lot of guilt over sending their parents to a professional physicality even when it is the best option. A lot of times it is hard to grasp the idea that they don't know the number of times you go and see them so you don't need to feel guilt for not being by their side every day.

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As an adult child of a parent with dementia, you've undoubtedly faced challenges with your parent - perhaps the care, the conversations or the realization that the relationship with your mom or dad has changed. Your rapport with your parent is not the same as it was. Your relationship is evolving and will continue to evolve as your parent travels down path of dementia.

The purpose of this guide, which was written by someone who was in your shoes, is to help you navigate this journey, so you live your life with no regrets; so you maintain a warm relationship with your parent, however different; and so you can help others who face similar challenges.

Dementia is a blanket term used to describe various disorders of the brain, all of which result in impairment of intellect, memory and personality. This is usually accompanied by changes in behavior and the gradual loss of the skills required to cope with the activities of daily living.

"Ambiguous loss" is a term used to describe the loss that an adult child may feel when the parent is physically present but may not be mentally or emotionally connected.

This is very different from the loss and grief of sudden death, as an example, where you clearly know that the person is gone. With a death, you are more likely to get support from family and friends and may eventually find closure through traditional mourning rituals and the natural grieving process. Ambiguous loss complicates grief. It may be hard for you to recognize this grief or know how to grieve when the abilities of the person with dementia have changed. Family and friends may not recognize your need to grieve the many losses you experience at different stages of the disease and therefore not provide you with the support you need in your ongoing caregiver role. Grief can be frozen, and it can put your life on hold. If you don't allow yourself to grieve or resume some of your regular activities, coping will be harder as the disease progresses. Recognizing these feelings and understanding the concept of ambiguous loss can help to ease the effects. With guidance and support, you can work through these feelings, begin to grieve the losses and stay connected to the person with dementia while also building your own strength and resilience.

As the disease progresses, the loss may be felt again and again. Perhaps during the last visit, you were able to carry on a conversation and during the next visit, your mom or dad couldn't string together more than a few words. You realize that as dementia worsens, you lose more of your parent.

"Since I lived across the country, I only visited my mom once a month over the course of three years. During the last year, the changes in her each month were astounding. Every visit I found a new person - she could carry on a conversation, then she could only speak in a few words and finally she could find only one word. While this was very sad, I knew the loss was inevitable, and I tried to connect with each new person whom I encountered every month. When there was no communication, I brought her favorite book and read it out loud. She continually smiled when she looked at me reading.Although our communication was only eye contact, she seemed to appreciate my presence."

Deciding that your parent should move into a skilled nursing or memory care facility was probably not an easy decision. Your parent may have fought with you about moving, and you may have felt guilty that your mom or dad now needs the skilled nursing care, which comes with less independence for your parent. Your guilt may increase if your parent has a difficult time adjusting to their new surroundings. These feelings are very natural and nearly every child has them.

Any change is dramatic for someone with dementia. Moving into new surroundings can be particularly traumatic. To ease the transition, a social worker suggests furnishing the new unit with familiar curios, photos and other furnishings with which your parent is accustomed. The familiar surroundings will help your parent adjust to the new environment more quickly.

The shadow box outside the unit door is a wonderful way to let the staff know a little about your parent. Highlights of their life, photos and other memorabilia also help your parent easily recognize their unit.

"My mom was admitted to the Lodge because she was coming out of the hospital. She seemed very depressed and was spending the day in bed. Lynn, the social worker, said that I should bring familiar pieces to the unit. But because I didn't know where she was going to live until the results of the evaluation, I hesitated. Once the evaluation was completed with the recommendation that my mom stay in the Lodge, I began moving things into the unit. My mom protested, saying that she didn't want anything. When she was at lunch one day, I moved my mom's favorite pieces in. When she came back from eating she was happy to see everything. Then I arranged with the staff to come in throughout that afternoon and comment on the furniture, pictures, etc., which they did. The change in my mom was transformational. Now her unit looked similar to her apartment and she was thrilled. She stopped spending her days in bed."

Your Role in Your Parent's Well-Being

Visiting your parent can be very hard. The role you played as a child is transitioning to a role where your parent is becoming the child. This can be very difficult to witness. Some adult children can't cope with this transition and choose not to visit their mom or dad. However, recognizing that this evolution is the journey of dementia, coming to terms with the changes and offering your parent companionship and support will be rewarding at the end.

Here are some tips for your visits even though the conversation might only be one way:

Keep your mom or dad up to date on family news.

Bring scrapbooks and reminisce about good times and significant events.

Sit outside in the courtyard.

Bring newspapers and magazines to look at together.

Play games that your mom or dad may have enjoyed in the past.

Bring others to visit.

Give your parent a hand or foot massage.

Style their hair.

Bring a DVD player and watch the videos.

"Years ago, my mom and I had taken a 10-day RV trip to 11 national parks. We had a marvelous time and laughed ourselves silly. I often brought the photos of the trip and talked about all the things we did. Although my mom could no longer speak, she was always smiling when I showed her the photos."

Some visits can be very difficult, especially when you see drastic changes in your parent.

Don't get despondent when visiting. Take pleasure in the small things - a smile, a laugh, a joke, a cuddle, a glimpse of recognition. Don't stop visiting because you think there is no point because your mom or dad doesn't appear to recognize you. Each day is different, and it is difficult to tell what the person is feeling but care staff say people always appreciate seeing visitors. Live for the moment - it does not matter that the person won't remember your visit - you will have hopefully brought pleasure and happiness whilst you were there."

Telephone and Video Contact

If your parent is able to talk, telephone visits can enhance your connection. Video visits add a further dimension.

"I put an old laptop in my mom's unit, which was connected to the internet. Then I used gotomypc to log into her computer and called myself on Skype and muted the audio. Then I called her on her hearing-impaired phone. I wanted to make sure that she saw me once or twice a day, so she wouldn't forget who I was even though I only visited once a month. And she never did."

Research indicates that music transcends dementia and touches people in a way that nothing else does. Try playing music for your mom or dad. Here are some amazing resources about the use of music with dementia patients.

Alive Inside - https://www.youtube.com/watch?v=Hlm0Qd4mP-I

https://www.youtube.com/watch?v=3mz9Vy_LNu8

https://www.youtube.com/watch?v=CrZXz10FcVM

Conversations: Understanding the Loss of Independence

As dementia progresses, your parent will continue to relinquish independence such as not having money, no lock on the door, the inability to come and go as they please, etc. Losing independence is especially hard on someone who was previously very independent.

The situation is exacerbated by the "helicopter child." Similar to the well-known helicopter parent where moms and dads hover over their children and direct their lives, helicopter children recognize the changing role between them and their parents and begin treating their parents as children - telling them what to do. Use your walker, sit down, drink your juice. These commands highlight the loss of independence as fewer decisions are made by your parent. While your directions are in your parent's best interest, turning these statements into questions gives your parent some control when you respect their answers. Do you want to use your walker? Do you want to sit down? Do you want to drink your juice?

Conversations without Words

According to research, communication has three components: 55 percent is visual, 38 percent is tone and seven percent is verbal. Over half of our communication is non-verbal. As your parent begins to lose the ability to speak, communication still occurs when you're with your parent. Touching may eventually become the primary way that you communicate.

Here are suggestions to improve communication with your parent:

Avoid the use of jargon or complicated explanations. Keep your conversation as simple as possible without patronizing or sounding childish.

Don't ask questions that begin with why. Your parent may find the reasoning involved in giving an answer difficult and become annoyed with themselves.

Be a good listener. Give your parent your full attention and resist the temptation to finish their sentences and talk down to them.

Talk at a slower pace so that your parent can grasp what is being said.

Maintain a calm and unhurried speech pattern.

The change in your parent can be shocking. Initially, before a dementia diagnosis, or even after, you may be inclined to shame your parent. Perhaps they no longer want to bath or brush their teeth. This is difficult to understand, especially if your mom or dad was fastidious about cleanliness, for example. However, shaming usually doesn't change your parent's decision. But it may make you feel guilty about trying to influence a behavior through shaming.

Leaving your parent can be a difficult time for both you and your mom or dad. Perhaps your parent has separation anxiety or increased challenging behaviors when you depart. You might want to schedule a visit around an activity in which you can leave while your parent is distracted. The staff can suggest the best time of day to visit.

My Slow Slide into Dementia

The following is a fictitious letter from a mother to her daughter about the mother's slow slide into the devastating decay that dementia inflicts on memory.

Dear Daughter,

During the past few years, we seem to have grown apart. I know that you're increasingly frustrated and upset with things that I've said and with my baffling actions. Let me try to explain.

My incessant criticizing of everything about you is because it's my only way of interacting with you, since I can no longer carry on a conversation. This is the reason why I constantly correct you...it's the closest that I can come to a dialogue between us.

When I don't invite you to sit with my friends at lunch as they do with their visiting children, it's not because I'm not proud of you as you must surmise, but because the words escape me to introduce you or talk about you.

When I embarrass you in front of people, it's because I don't recognize that my words will hurt you, and I only know that I'm grateful that some words actually tumble out of my mouth.

When things I say or do seem mean, I've been told that I've probably had a small stroke in the front part of my brain that's affected my judgment.

When I don't want to go to the movies or go shopping or do anything with you, it's because I'm not sure how to get there any longer, and I can't tell you the directions.

When you walk in after traveling for eight hours and I say that I need to watch the local news, it's because I can't find the words to converse with you; it's not because I'm not thrilled to see you.

When I do talk, it's usually something that I've fabricated, because those words seem to come easy...I believe it's the truth.

When you want to sleep late because you're on a different time zone, I wake you up early while I'm in the kitchen and you're close-by, because I need to stick to the schedule which I've known for years.

All the times that you called, and I said that I couldn't hear you or that I couldn't talk because I was getting ready to go to lunch or watch my favorite TV program, it wasn't because I didn't want a conversation, but because my words are lost.

When you say something funny, I don't laugh any longer, because the words don't have the nuance of humor for me.

When you do something nice, like walk in with flowers, and I don't thank you, it's because I can't express my feelings.

For over a decade, I've hidden my slow memory loss from you. You used to count down the days when we'd be together. I realize that now you probably dread the day you'll have to spend time with me. Please remember the time when I was kind, a great conversationalist and fun to be around.

My dementia has robbed us. But I'm counting on your mind to sustain great memories for both of us.

There's no doubt that the road ahead will present challenges. You may not recognize this person is your parent as the dementia progresses, but each encounter will be an opportunity to meet someone new, to connect again in a different way and to share experiences, so at the end of your parent's life you'll have no regrets on how you spent their last years.

"Over the years, as I've told people that I'm travelling to Florida to see my mom in a skilled nursing facility, people mention that their parent passed away. Then they invariably say, 'I wish I had spent more time with my mother.'"

I started my lecture to a class of graduate nurses studying the "Psychological Aspects of Aging" with the following case presentation:

The patient neither speaks nor comprehends the spoken word. Sometimes she babbles incoherently for hours on end. She is disoriented about person, place and time. She does, however, respond to her own name. I have worked with her for the past six months, but she still shows complete disregard for her physical appearance and makes no effort to assist in her own care. She must be fed, bathed and clothed by others. Because she has no teeth, her food must be pureed. Her shirt is usually soiled from almost incessant drooling. She does not walk. Her sleep pattern is erratic. Often, she wakes in the middle of the night, and her screaming awakens others. Most of the time she is friendly and happy, but several times a day she gets quite agitated without apparent cause. Then she wails until someone comes to comfort her.

I asked how the nurses would feel about taking care of such a patient. They used such words as "frustrated," "hopeless," "depressed" and "annoyed." When I said that I enjoyed it and thought they would too, the class looked at me in disbelief. Then I passed around a picture of the patient: my six-month-old daughter.

Why is it so much more difficult to care for a 90-year-old than a six-month-old with identical symptoms? The infant, the class and I agreed, represents new life, hope and almost infinite potential. The aged patient represents the end of life, with little chance for growth.

We need to change our perspective. Those who are ending their lives in the helplessness of old age deserve the same care and attention as those who are beginning their lives in the helplessness of infancy.

There are a number of support resources for you, which may include support groups. Here are a few:

1. ADEAR Center (https://www.nia.nih.gov/health/about-adear-center)

2. Alvin A. Dubin Alzheimer's Resource Center (www.alzheimersswfl.org)

3. Alzheimer Association (https://www.alz.org/)

4. Alzheimer Scotland (www.alzscot.org)

5. Alzheimer Society of Canada (www.alzheimer.ca)

6. Alzheimer's Foundation of America (https://alzfdn.org/)

7. Association for Frontotemporal Degeneration (https://www.theaftd.org/)

8. Banner Alzheimer's Institute (https://www.banneralz.org/)

9. Lewy Body Dementia Association (https://www.lbda.org/support)

10. Rosalind Carter Institute for Caregiving (http://www.rosalynncarter.org/)

Thank you, Mary Freye, RN, from the Alvin A. Dubin Alzheimer's Resource Center in Fort Myers, for your commitment, your work and your support in identifying important material to help adult children cope with their parents' dementia. Thank you, MaryAnne Sterling for a great list of support resources.

Written by Barbara Lewis, MBA (BarbaraLewis@JoansFamilyBillOfRights.com)

1. Letting Go without Giving Up, Jenny Henderson and Maureen Thom, Alzheimer Scotland, page 2

2. Ambiguous Loss and Grief in Dementia, Alzheimer's Society of Canada, 2013, page 2

3. Letting Go without Giving Up, Jenny Henderson and Maureen Thom, Alzheimer Scotland, page 20

4. Letting Go without Giving Up, Jenny Henderson and Maureen Thom, Alzheimer Scotland, page 23

5. Dr. Paul E. Ruskin in the Journal of the American Medical Association
Does your loved one have dementia or Alzheimer's? I answered all these questions, Yes, when my mother was diagnosed with Alzheimer's. What are your answers?

1. Are you frustrated with a loved one?

2. Do you feel as though you've grown apart from your loved one lately?

3. Do you feel as though your loved one is criticizing you more than previously?

4. Does your loved one prevent interaction with others while you are around?

5. Does your loved one embarrass you about things, which they say or do?

6. Does your loved one say things that seem mean?

7. Did your loved one stop doing things with you?

8. Does your loved one make excuses for not talking with you?

9. Does your loved say things that aren't true?

10. Does your loved one stick to a routine even when it's not feasible?

11. Has your loved one's sense of humor changed?

12. Do you feel that your loved one takes you for granted by not thanking you for things that you do?

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Guide for Adult Children of Parents with Dementia

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As an adult child of a parent with dementia, you've undoubtedly faced challenges with your parent - perhaps the care, the conversations or the realization that the relationship with your mom or dad has changed. Your rapport with your parent is not the same as it was.

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This is a blog by Cathy Cassata, a freelanced writer who forces on health education. Trying to connect to past memories you hold with your parents can help both patient and the child. Trying to find old music they like and showing photos can help bring moments of clarity. Person-centered care is when you focus on the patient over the disease.

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Remaining focused on the present, instead of grieving the past, and caring for caregivers are sometimes the best ways to help a parent living with Alzheimer's disease.

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Finding new ways to connect with a parent who is living with Alzheimer's can be meaningful for both you and them. Getty Images

Amy Calandra remembers riding in the car with her dad listening to the oldies station on the radio. She recalls the many Father's Days her family spent celebrating him at Six Flags Great America. She laughs about her dad's love of Corvettes and good jokes, and relishes in his ability to fix up her childhood home.

"He built all the cabinets in the garage to keep all the tennis rackets and skateboards and things organized. And with a couple friends, he built the deck off the back of our house and the entire hole to sink our above-ground swimming pool into," Calandra told Healthline. "He was strong and did so much; to see him go to this is heartbreaking."

Six years ago, her dad was diagnosed with Alzheimer's disease at 70 years old. Since then, his cognitive abilities have declined, and he has experienced intense physical symptoms such as difficulty getting up and walking.

"He started falling a lot, and then one time, he fell out of bed and my mom tried for over an hour to get him up until I got there to help," said Calandra.

A wheelchair eventually became necessary, and for the past 2 years he's been bedridden in hospice at home.

While he's forgetful and not at the mental capacity he was before diagnosis, Calandra says the physical changes came as the most shocking to her and her family.

"My mom's mom died of Alzheimer's, so I saw what it could do. My grandma was mostly affected mentally... I thought it would attack my dad mentally before seeing him physically deteriorate, but it has attacked the part of his brain that controls his body," she said.

While the disease progresses differently for each person, physical changes are often symptoms of mid- to late-stage Alzheimer's, says Ruth Drew, director of information and support services at the Alzheimer's Association.

"At some point, people can forget how to walk, can have balance problems, may need to use a walker but forget to use the walker so they get up without the walker and fall down... and at some point, they're not going to be able to walk," Drew told Healthline.

Many times, people with Alzheimer's eventually need help with toileting, dressing, and eating, she adds.

For adult children like Calandra, witnessing these changes can be devastating.

"It can be upsetting to be with a parent who raised you and you've known as robust and capable. To see them in the light of being dependent and incapable can bring up all kinds of feelings of grief," Tom Meuser, PhD, director of the Center for Excellence in Aging & Health at the University of New England, told Healthline.

This can be the case whether you have a close, supportive relationship with your parent or a complicated one.

"If you had a conflicted relationship with your parent, estrangement, or distance emotionally or physically, and now you're thrown into this situation where you have to care for someone you have mixed feelings about - perhaps in an intimate way like toileting and feeding - that can have a whole set of reactions attached to it," Meuser said.

For Calandra, that means dealing with feelings that stem from missing the father with whom she shared a close connection.

"He was a great dad and a funny person and I miss talking to him so much. It's a slow acceptance that he's not the same person I've always known; something that I struggle with every time I see him," she said.

Meuser points out that there is a point in the progression of Alzheimer's disease where the person has undergone psychosocial death - meaning who they have largely been most of their life is absent. This occurs because the person has lost his or her historical memory and lives only in the present.

"Forgetting children or spouses is a hallmark of psychosocial death. The body is there but the person is radically different. That is often a trigger for grief and loss, more so than bodily death in advanced dementia," he said. "By the time bodily death happens, there is a sense of relief. And there can be feelings of guilt too."

Despite the changes that occur with a loved one, Drew says connecting with them in a way that resonates with them can be meaningful for both parent and child.

"People with Alzheimer's can retain a core sense of self deep into the disease when their brain is still affected. There are things we can do to help support that rather than [create] an environment that shuts them down," she said.

For example, Drew recalls a woman who found that talking to her father about the next-door neighbors from her childhood, reading him his favorite poems, and playing him is favorite songs, resonated with him, and as a result brought her comfort during visits.

"Even though he couldn't say her name, he knew she was there for him and that she was one of his people. They were able to have a wonderful connection that was built on a lifetime of being family even until the end of his life," Drew said.

She refers to this approach as person-centered care - focusing on the person over the disease.

Calandra practices her own form of person-centered care by tapping into her father's love of humor.

"When I visit, I like to make him laugh. Even though his laugh is different, I know he's happy because he smiles and laughs when I say silly things," Calandra said. "I hold on to the fact that he still recognizes me and my voice."

In the process of trying to comfort a parent with Alzheimer's, sometimes the primary caregiver's well-being gets overlooked.

Calandra's mother is the main around-the-clock caregiver to her father.

Since he's in home hospice, a nurse visits twice a week to check in and clean his catheter. Another healthcare professional visits three times a week to bathe him. Her mom gets out of the house twice a week when a retired nurse's assistant comes to stay with Calandra's dad for 5 hours. During this time, she shops, runs errands, and goes to her own doctors' appointments.

"Day and night, it is stressful for her, but she wants to do everything for him, "Calandra said.

In spousal care situations like the one Calandra's parents face, Meuser said the healthy parent can put their own well-being in harm, and that caregivers are at increased risk for anxiety and depression.

"Caregiving is not only the time it takes to care and the act it takes to care, but there is real psychic stress with respect to witnessing change and decline and the prospect of impending death," said Meuser. "Often times [spouses who are caregivers] will carry a very heavy load and not share with their adult children how heavy that load is. The adult children only learn when there is a real collapse of the caregiver parent, and then they end up in the situation where they have two people needing help and care."

To support her mom, Calandra and her three siblings take turns visiting their parents.

"Many times, the visits are more for me and my mother because she needs interaction with people who are responsive and engaging. She's secluded and suffering in her own ways. Sometimes my siblings and I think she's being robbed of the good years she has left," Calandra said.

Drew said giving a caregiver a break like this is the best way you can help someone caring for a person with Alzheimer's. Also, taking on small chores such as cleaning, doing laundry, paying bills, providing lawn care, servicing the car, and picking up groceries can help in big ways.

"It's not about barking orders, but saying [something like], 'Mom, clearly there are things that you do that only you can do, but are there things that I can do that would be helpful or it doesn't matter who does them as long as they get done?'" said Drew.

Meuser agreed, noting that sometimes a more extended break is needed, such as one that can be achieved by putting a loved one in an adult daycare periodically.

Calandra's father receives 4 days of overnight respite care every 3 months. She says this is a time for her mom to see family and friends and recharge.

"It's a short time, but really important because it's the only time she can think about herself," said Calandra. "Sometimes (we) will go away for a few nights, and I know she enjoys that."

For family far or unable to visit often, providing emotional support is a simple way to support a caregiver, noted Drew.

"Let the person know how much you appreciate what they're doing and the fact that they're doing it is such a gift to the person with the disease and to the family. Caregivers feel isolated and that whatever they do they are failing, so [showing] appreciation... and supporting what they're doing rather than criticizing it means a lot," she said.

Calandra can attest. She says rather than challenging decisions their mom makes about her father's care, she focuses on showing up for her.

"I miss talking to my dad so much - about my life, and silly things and just everything. But I know he is not who he used to be," Calandra said. "It helps to focus on the time I have left with my mom."

Still, she admits it can be hard to focus on one parent over the other. While there can be guilt around spending time with a healthy parent when the other parent is ill, Drew says think about it in terms of human connection.

"We all need human connection in one way or another and helping people find connection that is meaningful to them and giving them the breaks that are helpful to them is what really matters," said Drew.

Meuser notes that those in late-stage Alzheimer's will not recognize that you did not prioritize them in certain moments when the caregiver needs your attention.

"The parent who is the caregiver is going to remember the support, and they need it," said Meuser. "There is no harm in prioritizing the caregiver parent in that situation."

For information about helping a caregiver, the Alzheimer's Association offers around-the-clock support through its online community and hotline (800-272-3900) as well as face-to-face support groups around the country.

"When it comes down to it, it's still the family that's providing the bulk of the care and carrying the heaviest burden of this disease, and that won't change until we find a way to treat Alzheimer's," Meuser said. "It requires constant messaging to support families to realize that there are structures to help you and to not let it overwhelm you to the point where you can't reach out."
Cathy Cassata is a freelance writer who specializes in stories about health, mental health, and human behavior. She has a knack for writing with emotion and connecting with readers in an insightful and engaging way. Read more of her work .

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Remaining focused on the present, instead of grieving the past, and caring for caregivers are sometimes the best ways to help a parent living with Alzheimer's disease. Amy Calandra remembers riding in the car with her dad listening to the oldies station on the radio.

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This is a Harvard academic study done about genetic testing and how it can seem like a blessing that would tell you whether or not you have the disease Alzheimer's. This is not the reality; It actually only tells you if you are at a higher risk for Alzheimer's. This can cause worry if you do have the gene but you really wouldn't need to because it doesn't mean that you would necessarily have Alzheimer's at any point in your life.

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Alzheimer's in the family - Harvard Health

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Thanks for visiting. Don't miss your FREE gift. The Best Diets for Cognitive Fitness, is yours absolutely FREE when you sign up to receive Health Alerts from Harvard Medical School Sign up to get tips for living a healthy lifestyle, with ways to fight inflammation and improve cognitive health, plus the latest advances in preventative medicine, diet and exercise, pain relief, blood pressure and cholesterol management, and more.

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This was a graphic novel by Sarah Leavitt that depicted her experience being a caregiver to her mother. She created the novel to help raise awareness about the effects on not only the patient but the family. It helps represent the different emotions and coping skills children go through to try and understand the illness. Sarah would take notes on her mother's story to help her try and understand what she is going through. The story also dives into the different ways people can react after grieving for a loved one for so long.

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This is a public article from the Alzheimer's Association. This talks about caregivers being put at a higher risk of anxiety and stress. Many of the symptoms caregivers face resemble the process of grief. The disease when starting to progress puts the caregiver's brain in a reaction of grief.