OBJECTIVE: To examine the association of plasma levels of total cholesterol, low density lipoproteins (LDL), and high density lipoproteins (HDL) with the risk of developing Alzheimer disease (AD). BACKGROUND: Several studies have suggested an increased risk of Alzheimer disease among subjects with high cholesterol levels during midlife. In addition, there is evidence that cholesterol lowering drugs (statins) may reduce the risk of dementia. DESIGN?METHODS: Participants are volunteers in the Baltiimore Longitudinal Study of Aging (BLSA), a multidisciplinary study of normal aging conducted by the National Institute on Aging. Cholesterol and lipid levels were collected from BLSA participants during their biennial visit between 1983 and 1998. Clinical diagnoses were made according to DSM-III-R criteria for dementia and NINCDS-ADRDA criteria for probable or possible AD. 988 BLSA participants who were older than 60 years of age and had plasma cholesterol and lipid levels were included in the analyses. We used Cox proportional hazards models to estimate the relative risk (RR) and confidence intervals (CI) of developing AD associated with plasma levels (mg/dl) of total cholesterol, LDL, HDL, and LDL/HDL ratio at different time periods up to 9 years before the diagnosis of AD. Separate analyses were performed for each of the intervals before diagnosis. Chronological age was used as the time scale in the Cox models. The most recent cholesterol and lipid level within each interval was included as a time-dependent variable in the models. The analyses adjusted for gender, education, and use of cholesterol lowering drugs (statins). RESULTS: High levels of LDL or a high ratio of LDL/HDL years before diagnosis was associated with an increased risk of AD. 7 to 9 years before diagnosis the RR for LDL levels > 160 mg/dl vs. < 130 mg/dl was 2.65 (95%CI=1.33-5.31, p=.006) while the RR for an LDL/HDL ratio > 3 was 1.82 (95%CI-1.02-3.25, p-0.04). 5 to 7 years before diagnosis, there was also a significant increase in the risk of AD in subjects with a high ratio of LDL/HDL levels (RR=1.76, 95%CI=1.04-2.99, p=.04). We also found an increased risk of AD among subjects with low levels of HDL and among subjects with high cholesterol levels 7 to 9 years before diagnosis but this increase was not statistically significant. The RR for HDL levels < 50 mg/dl was 1.62 (95%CI=0.86-3.33, p=0.14) and the RR for total cholesterol levels > 200 mg/dl was 1.60 (95%CI=0.89-2.90, p=.12). Adjustment for use of statins did not have an effect on the association between risk of AD and lipid levels up to 5 years before diagnosis. Statin information was not available at longer intervals before diagnosis because of the infrequent use of these compounds in those time periods. Adjustment for presence or absence of an ɛ4 allele of Apolipoprotein E did not change the association. CONCLUSIONS: Our findings support previous suggestions that high levels of LDL or a high ratio of LDL/HDL may increase the risk of AD years later. Total cholesterol or HDL levels appear to be less relevant to AD but further studies are necessary. Supported by: extramural grants AG05146 and AG08325 and the Intramural Research Program of the National Institute on Aging Disclosure: Maria M. Corrada has nothing to disclose.

OBJECTIVE: To study the association between intake of antioxidant vitamins, calcium, and certain beverages and all-cause mortality BACKGROUND: Studies have suggested that certain diets and mild to moderate alcohol intake can protect against some chronic diseases and all-cause mortality. However, studies of these factors in the oldest old are limited. DESIGN/METHODS: Participants are elderly adults from the Leisure World Cohort Study, a population-based prospective investigation in a California retirement community. Between 1981 and 1985, 13979 subjects completed a baseline mailed survey about lifestyle and medical history. Diet information was collected with a food-frequency questionnaire that included beverages and 58 foods (or food groups) that are common sources of dietary vitamins A, C and calcium. Cox proportional hazards analyses were performed to estimate the risk of mortality associated with intake of the following: vitamins C and A (diet plus supplements), vitamin E (supplements), calcium (diet), coffee (regular and decaffeinated), tea, and alcohol. The model adjusted for the potential confounding effects of gender, baseline age, smoking, exercise, body mass index (BMI), and history of several medical conditions typically associated with decreased survival (hypertension, angina, myocardial infarction, stroke, diabetes, fractures, and cancer). The relative risks (RR) for all the variables were estimated simultaneously in one model. Because of the many concurrent estimates, we used a significance level of 0.001. RESULTS: As of October 2002, there were 9869 deceased participants. Subjects were excluded from analyses if their information for the variables of interest was missing (n=983). The average age at baseline of the 12,996 analyzed participants was 73.6 (range=44-101) and their average follow-up was 12.8 years (range = 0-21). After adjusting for age, gender, smoking, exercise, BMI, and medical histories, alcohol intake (Rr=0.91 for +/-1 drink/day; Rr=0.85 for>1 drink/day vs. no intake) and the highest category of caffeinated coffee drinking (Rr=0.90 for>1 cup/ day vs. no intake) were associated with a reduction in all-cause mortality. Wine appeared to be the specific type of alcohol most responsible for the reduction (Rr=0.88 for +/-1 glass/day; Rr=0.86 for>1 glass/day vs. no wine intake). Intake of antioxidant vitamins, calcium, or tea was not associated with mortality. The RRs for medium and high tertiles respectively vs. low tertile were 0.99 and 0.97 for total vitamin A; 1.00 and 1.01 for total vitamin C; 0.96 and 0.97 for vitamin E supplements; 1.02 and 1.07 for calcium. For +/-1 cup/day and>1 cup/day vs. no tea, the RRs were 0.98 and 0.96. CONCLUSIONS: Mild to moderate alcohol drinking, particularly wine, as well as high coffee consumption were related to a decreased risk of all-cause mortality. Supported by: NIA grant R01AG21055 and NCI grant R01CA32197

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.

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.

Supported By: This investigation was supported by NIA grant RO1AG21055. OBJECTIVE: To report the level of dependence in Activities of Daily Living (ADLs) and Instrumental Activities of Daily Living (IADLs) in non-demented community dwelling ninety year-olds. BACKGROUND: Little is known about the functional abilities of community-residing oldest-old, the fastest growing segment of the population. METHODS: Eighty nine men and women from the 90+ Study, a population-based investigation of individuals 90 years or older residing in Southern California. Subjects were excluded if they had a Mini-Mental State Examination (MMSE) score of less than 24, or were missing data on any of the relevant variables. Five ADLs (moving about indoors, bathing, eating, continence, and dressing) and five IADLs (doing finances, shopping, traveling out of the neighborhood, preparing meals, and using the telephone) were assessed by self-report from each subject. Each of the ten items was scored as: 0 (independent), 1 (difficult), 2 (needs some assistance), or 3 (dependent). Subjects were considered independent if they had scores of 0 or 1, and dependent if they had scores of 2 or 3 on an item. RESULTS: Sixty seven percent of subjects were women. Fifty six percent lived alone, 20% had a college degree or higher, and mean age was 93.7 years (range 90 to 100). Seventy eight subjects (87.6%) were independent in all five ADLs. Of the 12.4% who needed help with ADLs, assistance was required most frequently for bathing (73%). Sixty two (69.7%) were independent in all five IADLs. Of the 30.3% who needed help on IADLs, assistance was required most frequently for shopping (85%), traveling (48%), and doing finances (37%). CONCLUSION: Most community-residing non-demented 90+ year olds in this study were independent in all ADLs and IADLs. Dependency frequently involved activities that appeared to have a mobility or visual acuity component. Further research is needed to investigate the determinants of functional loss in the oldest-old.

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.

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.