Prior endogenous and exogenous estrogen and incident dementia in the 10th decade of life: The 90+ Study.

Objective: This study aimed to investigate the association of endogenous and exogenous estrogen exposure with risk of incident dementia in the oldest-old (age 90+ years).Methods: Participants were part of The 90+ Study, a longitudinal study begun in 2003 of aging and dementia among people aged 90+ years. Menstrual, reproductive, and menopausal data were collected in the 1980s as part of the population-based Leisure World Cohort Study. Cognitive status at baseline was determined from an in-person neurological evaluation with biannual follow-up through June 2019. Hazard ratios (HRs) of dementia associated with estrogen-related variables were estimated using Cox regression analysis. No adjustment was made for multiple comparisons.Results: A total of 424 women without dementia at baseline had at least one follow-up evaluation. The mean age was 68.5 years at enrollment in the Leisure World Cohort Study, 93.2 years at enrollment in The 90+ Study, and 96.5 years at last follow-up. During follow-up (mean 3.4 years) dementia was diagnosed in 209 (49%) participants. No individual menstrual, reproductive, menopausal, or estrogen replacement variable was associated with risk of incident dementia after age 90 years. However, women with a high endogenous estrogen exposure index (summarizing exposure from menarche to menopause) had a non-significant 25% lower risk (HR = 0.75, 95% confidence interval 0.53-1.06).Conclusions: Prior exposure to estrogen, endogenous or exogenous, had little effect on risk of dementia in the 10th decade of life.

Prevalence of dementia after age 90: results from the 90+ study.

BACKGROUND: Although the prevalence of dementia increases with age from ages 65 to 85, whether this increase continues after age 90 is unclear. Most studies reporting on dementia prevalence do not have sufficient participants to estimate prevalence for specific ages and sexes above age 90. Here, we estimate age- and sex-specific prevalence of all-cause dementia in the oldest-old, those aged 90 and older. METHODS: Participants are 911 elderly from The 90+ Study, a population-based study of aging and dementia in people aged 90 and above. Dementia was diagnosed using in-person examinations as well as telephone and informant questionnaires. RESULTS: The overall prevalence of all-cause dementia was higher in women (45%, 95% CI = 41.5-49.0) than men (28%, 95% CI = 21.7-34.2). Among women, prevalence increased with age after age 90, essentially doubling every 5 years. A lower prevalence of dementia was significantly associated with higher education in women but not in men. CONCLUSIONS: In a very large sample of participants aged 90 and older, prevalence of all-cause dementia doubled every 5 years for women but not men.

No advantage of A beta 42-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies.

INTRODUCTION: Observational studies show reduced incidence of Alzheimer dementia (AD) in users of nonsteroidal anti-inflammatory drugs (NSAIDs). One hypothesis holds that the subset of NSAIDs known as selective A beta(42)-lowering agents (SALAs) is responsible for this apparent reduction in AD risk. METHODS: We pooled individual-level data from six prospective studies to obtain a sufficient sample to examine AD risk in users of SALA vs non-SALA NSAIDs. RESULTS: Of 13,499 initially dementia-free participants (70,863 person-years), 820 developed incident AD. Users of NSAIDs (29.6%) showed reduced risk of AD (adjusted hazard ratio [aHR] 0.77, 95% CI 0.65-0.91). The point estimates were similar for SALAs (aHR 0.87, CI 0.72-1.04) and non-SALAs (aHR 0.75, CI 0.56-1.01). Because 573 NSAID users (14.5%) reported taking both a SALA and non-SALA, we examined their use alone and in combination. Resulting aHRs were 0.82 (CI 0.67-0.99) for SALA only, 0.60 (CI 0.40-0.90) for non-SALA only, and 0.87 (CI 0.57-1.33) for both NSAIDs (Wald test for differences, p = 0.32). The 40.7% of participants who used aspirin also showed reduced risk of AD, even when they used no other NSAIDs (aHR 0.78, CI 0.66-0.92). By contrast, there was no association with use of acetaminophen (aHR 0.93, CI 0.76-1.13). CONCLUSIONS: In this pooled dataset, nonsteroidal anti-inflammatory drug (NSAID) use reduced the risk of Alzheimer dementia (AD). However, there was no apparent advantage in AD risk reduction for the subset of NSAIDs shown to selectively lower A beta(42), suggesting that all conventional NSAIDs including aspirin have a similar protective effect in humans.

Calcium channel blockers and risk of AD: the Baltimore Longitudinal Study of Aging.

OBJECTIVE: To investigate the association between use of calcium channel blockers (CCB), dihydropyridine (DHP) or nondihydropyridine (nonDHP) type CCB and risk of developing Alzheimer's Disease (AD) or mortality. There is evidence suggesting that calcium plays a key role in changes in the brain leading to AD. Previous reports suggest a possible role for CCB in the treatment of AD. However, there are some indications that CCB increase mortality in patients with cardiac disease. METHODS: Subjects were 1092 participants in the Baltimore Longitudinal Study of Aging (BLSA) older than 60 years of age. Data on CCB use was collected prospectively for up to 19 years. Cox proportional hazards regression was used to estimate relative risks (RR) and confidence intervals (CI) of AD and mortality associated with use of CCB or use of only DHP or nonDHP-CCB. Analyses were adjusted for gender, education, smoking, blood pressure and history of heart problems. RESULTS: Use of DHP-CCB was not associated with a significantly reduced risk of AD compared to non-users, although the estimate of the RR was low with DHP-CCB (RR = 0.30, 95% CI = 0.07-1.25, P = 0.10). Use of nonDHP-CCB was not associated with reduced risk of AD and the estimate of the RR risk was close to one (RR = 0.82, 95% CI = 0.37-1.83, P = 0.63). In addition, there was no increase in mortality among users of DHP-CCB (RR = 0.64, 95% CI = 0.32-1.29, P = 0.21) or nonDHP-CCB (RR = 1.10, 95% CI = 0.65-1.87, P = 0.72). CONCLUSION: Users of DHP-CCB and nonDHP-CCB in this study did not have a significantly reduced risk of AD.

Visual memory predicts Alzheimer's disease more than a decade before diagnosis.

BACKGROUND: Recent studies have suggested that AD may reflect a chronic process that begins many years before the clinical expression of dementia. The current study examines premorbid Benton Visual Retention Test (BVRT) and Wechsler Adult Intelligence Scale-vocabulary (WAIS-voc) test scores in order to determine whether long-term deficits in these tests can predict the development of AD decades later in the Baltimore Longitudinal Study of Aging (BLSA). METHOD: Participants are volunteers from the BLSA, a multidisciplinary study of normal aging conducted by the National Institute on Aging. A total of 1,425 BLSA participants who were older than 60 years were included in the analyses. Cox proportional hazards models were used to estimate the relative risk of developing AD associated with BVRT and WAIS-voc scores at different time periods up to 20 years before the diagnosis of AD. RESULTS: The relative risks for 6 or more BVRT errors vs less than 6 errors at 1 to 3, 3 to 5, 5 to 10, and 10 to 15 years before the diagnosis of AD were 5.69, 2.11, 1.76, and 1.83 (p < 0.05). The relative risk for 15 or more years before diagnosis was not significant (p > 0.10). WAIS-voc scores were not significantly associated with the risk of AD in any time period. CONCLUSIONS: A greater number of errors on the BVRT is associated with an increased risk of AD up to 15 years later. Poor visual memory performance may represent an early expression of AD years before diagnosis. This result suggests the need to continue to revise views on the natural history of AD and the possibility of an increased window of opportunity for preventive treatment before definitive diagnosis.

A prospective study of estrogen replacement therapy and the risk of developing Alzheimer's disease: the Baltimore Longitudinal Study of Aging.

Previous reports have suggested that estrogen replacement therapy (ERT) in women may exert a protective effect on their risk of developing Alzheimer's disease (AD). We investigated this relationship in the Baltimore Longitudinal Study of Aging (BLSA), a prospective multidisciplinary study of normal aging conducted by the National Institute on Aging. The sample consisted of 472 post- or perimenopausal women followed for up to 16 years in the BLSA. We documented ERT prospectively at each BLSA visit, and we categorized women who had used oral or transdermal estrogens at anytime as ERT users. We used Cox proportional hazards models with time-dependent covariates to estimate the relative risk of developing AD after ERT as compared with women who had not used estrogen replacement. Approximately 45% of the women in the cohort had used ERT, and we diagnosed 34 incident cases of AD (NINCDS/ADRDA criteria) during follow-up, including nine estrogen users. After adjusting for education, the relative risk for AD in ERT users as compared with nonusers was 0.46 (95% CI, 0.209-0.997), indicating a reduced risk of AD for women who had reported the use of estrogen. Our data did not show an effect for duration of ERT usage. Our finding offers additional support for a protective influence of estrogen in AD. Randomized clinical trials are necessary to confirm this association, which could have significant public health impact.

Risk of Alzheimer's disease and duration of NSAID use.

In a longitudinal study of 1,686 participants in the Baltimore Longitudinal Study of Aging, we examined whether the risk of Alzheimer's disease (AD) was reduced among reported users of aspirin or other nonsteroidal anti-inflammatory drugs (NSAIDs). In addition, we examined use of acetaminophen, a pain-relief medication with little or no anti-inflammatory activity, to assess the specificity of the association between AD risk and self-reported medications. Information on use of medications was collected during each biennial examination between 1980 and 1995. The relative risk (RR) for AD decreased with increasing duration of NSAID use. Among those with 2 or more years of reported NSAID use, the RR was 0.40 (95% confidence interval [CI]: 0.19-0.84) compared with 0.65 (95% CI: 0.33-1.29) for those with less than 2 years of NSAID use. The overall RR for AD among aspirin users was 0.74 (95% CI: 0.46-1.18), and no trend of decreasing risk of AD was observed with increasing duration of aspirin use. No association was found between AD risk and use of acetaminophen (RR = 1.35; 95% CI: 0.79-2.30), and there was no trend of decreasing risk with increasing duration of use. These findings are consistent with evidence from cross-sectional studies indicating protection against AD risk among NSAID users and with evidence suggesting that one stage of the pathophysiology leading to AD is characterized by an inflammatory process.

Sources of variability in prevalence rates of Alzheimer's disease.

OBJECTIVE: To investigate potential methodological reasons for the differences in published Alzheimer's disease (AD) prevalence rates. BACKGROUND: Studies reporting prevalence rates of AD have been published worldwide. These rates differ considerably, but may greatly reflect methodological differences. METHODS: All studies published between 1984 and 1993 that reported age-specific AD rates and sample sizes were included. Logistic regression identified variables that contribute to the variation in rates. Estimates of extrabinomial variation were also calculated. RESULTS: Studies characterized by the following features yielded significantly higher rates: inclusion of mild cases, use of laboratory studies, ascertainment of a sample rather than the total population, inclusion of both urban and rural populations, non-use of computerized tomography (CT) scans, non-use of the Hachinski Ischemic Score, and no adjustment for false negatives. The odds of having AD increased 18% for every year of age. The variation in the age-specific prevalence rates of AD was approximately 15 times that expected by sampling variation. However, approximately 76% of this excess variation in rates could be accounted for by methodological differences. CONCLUSIONS: After accounting for age, much of the variability in prevalence rates of AD in the published literature may be explained by differences in methodology. Some unexplained variation in prevalence rates, however, still remains.

Reliability of the Blessed Telephone Information-Memory-Concentration Test.

In-person cognitive evaluations can be costly and labor intensive in geographically widespread populations. Reliable telephone instruments that screen for cognitive status would greatly facilitate epidemiologic and other longitudinal studies. We evaluated the reliability of the Blessed Information-Memory-Concentration (IMC) test when administered by telephone. Eighty-four subjects with a wide range of cognitive abilities were administered the Blessed IMC twice over a 3-week interval. Forty-nine of the subjects were administered the test both by telephone and in-person, and 35 of the subjects were tested twice by telephone. Spearman's rank correlation was used to compare scores of the different administrations (.96; P < .001) and to examine test-retest reliability (.96; P < .001). The Blessed Telephone IMC (TIMC) test exhibits excellent reliability both when compared to in-person administration as well as in test-retest results. The Blessed TIMC appears to be a practical instrument for population and longitudinal studies when in-person assessment is not feasible.

A validation study of the Dementia Questionnaire.

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.