The oldest-old (people over age 90) are the fastest growing segment of the population in Asia and most of the world. With age as the strongest risk factor for dementia and AD, the oldest-old portend enormous public health, economic and social challenges. Investigations of cognition in this age group can provide clues to our understanding of dementia and cognitive loss at all ages. Intriguingly, about half of non-demented oldest-old have high levels of AD pathology at autopsy, but nonetheless maintain good cognitive performance during life. These individuals appear resilient to the deleterious effects of these neuropathologic changes. Conversely, approximately half of demented individuals in this age group are deemed to have insufficient amounts of any neuropathologic changes factor and clinical pathological investigations from The 90+ Study, a longitudinal population-based study of more than 1600 oldest-old based in Southern California, USA, will be presented. The impact of reducing or eliminating Alzheimer disease in this age group will be quantified. Finally, Preventing Cognitive Decline and Dementia, a recent report from the National Academies of Science, Engineering and Medicine, will be summarized. Growing understanding of AD and other dementia-associated brain changes will provide strategies to maintain memory and cognitive abilities at all ages.

Calcium homeostasis changes are associated with brain aging. Cytotoxic events produce elevated intracellular calcium via numerous mechanisms, such as changes in calcium channels. Several clinical trials have explored a possible therapeutic role of calcium channel blockers (CCB) in Alzheimer’s Disease (AD). We studied possible preventive effects of CCB in development of AD in a prospective longitudinal study. Methods: In the first analysis, all active subjects between 1980-96 from the BLSA were included. During follow up, 108 of the subjects were diagnosed with AD. Since newer CCB, which are likely to pass the blood brain barrier were introduced in the late 80s, we performed a 2nd analysis that was restricted to the 1087 subjects who were active during 1990-96. During follow up, 59 of these subjects were diagnosed with AD. Data on use of CCB was obtained prospectively by self-report at each BLSA visit. Cox proportional hazards models were used to estimate the risk of developing AD associated with the use of CCB. Results/Conclusion: In both analyses the use of CCB did not result in a significantly lower risk of AD (analysis 1: RR=0.96; p-.91; analysis 2: RR=0.56; p=.23 respectively), although there was a non-significant trend for decreased relative risk in the 2nd analysis. Follow up studies are needed with more detailed analysis of the type of CCB used and/or length of usage.

Objective: To examine predictors of wight change in subjects with moderate Alzheimer’s disease (AD) Methods: Subjects were 118 outpatients meeting NINCDS-ADSDA criteria for AD at the Johns Hopkins Alzheimer’s Disease Research Center, and having weight recorded at baseline and 18 or 24 months follow-up. Binary outcome measurements of > 4% weight loss, > 4% weight gain, and weight stability were computed from each subject’s baseline. Independent variables were sex, age, body, mass index (BMI), use of antidepressants (primarily tricyclics), neuroleptics pr both, Mini-mental State exam score, a dependency scale, Hamilton depression, incontinence, gait disturbance, and nursing home placement, Logistic regression analysis adjusting for age, sex, and BMI was used. Results: Weight loss was associate with incontinence (odds ratio (OR)=3.2, confidence interval (CI)=1.3-7.5) and nursing home placement (OR=2.7, CI-1.0-7.3). Antidepressant use increased the likelihood of weight stability (OR=3.5, CI=1.3-9.8) and nursing home placement decrease the likelihood (OR=0.3, CI=0.1-0.9). Only BMI was associated with weight gain (OR=0.9, CI=0.8-1.0). No outcome was significantly associated with age, sex, or the other variables. Conclusions: Significant weight loss in AD patients occurs with incontinence and nursing home placement. Use of tricyclic antidepressants to treat depression, dysthymia, or behavior problems is correlated with weight stability. Further study is needed to evaluate other antidepressants and interventions for weight loss in AD patients.

Objectives

The goal of this study was to project the future prevalence and incidence of Alzheimer's disease in the United States and the potential impact of interventions to delay disease onset.

Methods

The numbers of individuals in the United States with Alzheimer's disease and the numbers of newly diagnosed cases that can be expected over the next 50 years were estimated from a model that used age-specific incidence rates summarized from several epidemiological studies, US mortality rates, and US Bureau of the Census projections.

Results

in 1997, the prevalence of Alzheimer's disease in the United States was 2.32 million (range: 1.09 to 4.58 million); of these individuals, 68% were female. It is projected that the prevalence will nearly quadruple in the next 50 years, by which time approximately 1 in 45 Americans will be afflicted with the disease. Currently, the annual number of new incident cases in 360,000. If interventions could delay onset of the disease by 2 years, after 50 years there would be nearly 2 million fewer cases than projected; if onset could be delayed by 1 year, there would be nearly 800,000 fewer prevalent cases.

Conclusions

As the US population ages, Alzheimer's disease will become an enormous public health problem. interventions that could delay disease onset even modestly would have a major public health impact.

Objective: To prospectively examine the relationship between glucose/insulin/body mass index (BMI) measurements and the development of Alzheimer’s disease (AD). Background: Previous investigations have suggested that higher plasma glucose may protect against the development of AD. These studies, however, examined AD patients after dementia diagnosis and may not be relevant to risk of developing AD. Methods: 2321 men and women from the Baltimore Longitudinal Study of Aging (BLSA), aged 41 to 96, who had biennial glucose determinations (fasting plasma glucose, 2 hr post prandial glucose, insulin area, and BMI) were included in the sample. Data from 3-6 yrs prior to diagnosis of AD (NINCDS criteria) was analyzed using Cox Proportional Hazards. Results: There was no relationship between fasting, 2 hr plasma glucose or insulin area and the development of AD in this cohort. Higher BMI was associated with a lower risk of AD 3 yrs before diagnosis of dementia, but was no longer significant 6 yrs prior diagnosis. Diabetes was less frequent in patients with AD (2.8%) than in controls (5%). Conclusion” BMI, but not plasma glucose or insulin levels, may be related to risk of developing AS. Previous results suggesting a relationship may reflect metabolic, nutritional or activity changes that take place after symptom onset.

Objective

To examine whether the association between clinical Alzheimer disease (AD) diagnosis and neuropathology and the precision by which neuropathology differentiates people with clinical AD from those with normal cognition varies by age.

Methods

We conducted a cross-sectional analysis of 2,014 older adults (≥70 years at death) from the National Alzheimer's Coordinating Center database with clinical diagnosis of normal cognition (made ≤1 year before death, n = 419) or AD (at ≥65 years, n = 1,595) and a postmortem neuropathologic examination evaluating AD pathology (neurofibrillary tangles, neuritic plaques) and non-AD pathology (diffuse plaques, amyloid angiopathy, Lewy bodies, macrovascular disease, microvascular disease). We used adjusted logistic regression to analyze the relationship between clinical AD diagnosis and neuropathologic features, area under the receiver operating characteristic curve (c statistic) to evaluate how precisely neuropathology differentiates between cognitive diagnoses, and an interaction to identify effect modification by age group.

Results

In a model controlling for coexisting neuropathologic features, the relationship between clinical AD diagnosis and neurofibrillary tangles was significantly weaker with increasing age (p < 0.001 for interaction). The aggregate of all neuropathologic features more strongly differentiated people with clinical AD from those without in younger age groups (70-74 years: c statistic, 95% confidence interval: 0.93, 0.89-0.96; 75-84 years: 0.95, 0.87-0.95; ≥85 years: 0.83, 0.80-0.87). Non-AD pathology significantly improved precision of differentiation across all age groups (p < 0.004).

Conclusion

Clinical AD diagnosis was more weakly associated with neurofibrillary tangles among the oldest old compared to younger age groups, possibly due to less accurate clinical diagnosis, better neurocompensation, or unaccounted pathology among the oldest old.

Objective

To determine the validity of the Dementia Questionnaire (a semistructured informant interview) for the diagnosis of dementia.

Design

Comparison of dementia status determined by a telephone-administered informant questionnaire with the criterion standard of clinical diagnosis established by examination and laboratory studies.

Setting

Gerontology Research Center, the Baltimore Longitudinal Study of Aging.

Subjects

Volunteer cohort of 42 men and 32 women aged 68 to 97 years. Subjects were selected from strata defined by Blessed Information Memory Concentration Test scores, with oversampling of borderline scores (3 to 10).

Main outcome measures

Sensitivity and specificity of the Dementia Questionnaire in comparison with the criterion standard of clinical diagnosis.

Secondary outcome measure

Interrater reliability (kappa coefficient).

Results

Sensitivity and specificity for dementia were 100% and 90%, respectively. Most false-positive findings were from subjects with cognitive impairment that did not meet criteria for dementia (Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition. Interrater reliability was high (kappa = 0.83).

Conclusion

The Dementia Questionnaire can be used effectively in research studies to screen for dementia.