Janet L. Cobb

Incidence of dementia and probable Alzheimer's disease in a general population The Framingham Study

objective: To determine the incidence of dementia and Alzheimers disease (AD) in a general population sample. Background: Utilizing subjects in the Framingham Study cohort determined to be free of dementia in 1976 to 1978, or on biennial examination 17 in 1982, all new cases of dementia arising in this cohort over a maximum of 10 years of follow-up were ascertained. Methods: On biennial examination 14/15, a screening neuropsychologic examination was administered to 2,117 subjects, and cases of probable prevalent dementia were identified. Beginning on examination 17 and on all successive biennial examinations, a Mini-Mental State Examination was administered. Subjects previously free of dementia and falling below age-education levels were evaluated by a neurologist and neuropsychologist to determine if dementia was present and to ascertain the dementia type using standard criteria. Results: Five-year incidence of dementia increased with age, doubling in successive 5-year age groups. Dementia incidence rose from 7.0 per 1,000 at ages 65 to 69 to 118.0 per 1,000 at ages 85 to 89 for men and women combined. Incidence of probable AD also doubled with successive quinquennia from 3.5 at ages 65 to 69 to 72.8 per 1,000 at ages 85 to 89 years. Incidence of dementia and of probable AD did not level off with age and was not different in men and women. Conclusions: In a general population sample, we determined incidence of dementia and of probable AD and will use these incident cases for study of precursors and natural history in this elderly cohort, which has been under close surveillance for over 40 years.

Apolipoprotein E element 4 association with dementia in a population-based study: The Framingham Study

Apolipoprotein E type 4 allele (apoE epsilon4) is associated with Alzheimers disease (AD) in the late-onset familial form and in sporadic cases, but the age-associated risk in a randomly sampled elderly population is not established. We examined the association of apoE epsilon4 with AD and other dementias (mainly multi-infarct or dementia following stroke) in 1,030 persons aged 71 to 100 years in the population-based Framingham Study cohort. Kaplan-Meier survival analysis revealed that 55% of the apoE epsilon4/epsilon4 homozygotes developed AD by age 80, whereas 27% of apoE epsilon3/epsilon4 heterozygotes developed AD by age 85, and 9% of those without a 4 allele developed AD by age 85 years. In comparison with persons without a 4 allele, the risk ration for AD was 3.7 (95% CI = 1.9 to 7.5) for apoE epsilon3/epsilon4 heterozygotes and 30.1 (95% CI = 10.7 to 84.4) for apoE epsilon4 homozygotes. ApoE epsilon2 (2/2, 2/3, or 2/4 genotypes) was associated with an absence of AD. One-half (n=21) of the 43 AD patients were either homozygous or heterozygous for apoE epsilon4. We found evidence for an association of apoE epsilon4 with other dementia, primarily multi-infarct dementia and stroke. The risk ratio was 2.3 (95% CI = 0.9 to 6.1) for non-AD dementias among persons with apoE epsilon3/epsilon4. Although the apoE epsilon4 allele is a potent risk factor for AD and may be associated with other forms of dementia, most apoE epsilon4 carriers do not develop dementia, and about one-half of AD is not apoE epsilon4 associated. The low positive predictive value of this marker (0.10) suggest that use of apoE genotyping as a screening test for AD is not supported.

The effect of education on the incidence of dementia and Alzheimer's disease in the Framingham Study

Objective: To evaluate whether low educational attainment is a risk factor for the incidence of dementia and Alzheimers disease (AD) in the Framingham Study and to determine whether age at onset of dementia is earlier in persons with low educational levels. Design: A community-based cohort was studied longitudinally for the development of dementia. Diagnosis was made according to strict criteria by two neurologists and a neuropsychologist. Subtype of dementia and year at onset were determined. Incidence rates were compared in three education groups: less than grade school, less than high school, and more than equals high school. Participants: A total of 3,330 men and women aged 55 to 88 years. Results: During 17 years of follow-up, 258 incident cases of dementia, including 149 AD cases, were identified. Unadjusted incidence rates were significantly elevated (p less than 0.05) for dementia and non-AD dementia among the least educated. The age-adjusted relative risk for subjects with a grade school education or less compared with those who earned a high school diploma was 1.31 (95% confidence interval [CI], 0.90 to 1.90) for dementia generally, 1.04 (95% CI, 0.62 to 1.74) for AD, and 1.75 (95% CI, 1.03 to 2.98) for non-AD dementia. Age at onset of dementia did not vary by educational attainment. Conclusions: After age adjustment, low educational attainment was not a significant risk factor for the incidence of dementia generally or of AD. Low educational attainment was associated with increased risk of non-AD dementia, perhaps because of deleterious smoking habits and other risk factors for stroke in the least-educated individuals. Adequately adjusting for age and examining subtypes of dementia are important in assessing the influence of education on dementia incidence. NEUROLOGY 1995;45: 1707-1712

Physical activity and mortality in women in the Framingham Heart Study.

Men who are more active live longer, but it is not clear if the same is true for women. We monitored 1404 women aged 50 to 74 who were free of cardiovascular disease. We assessed physical activity levels and ranked subjects into quartiles. After 16 years, 319 (23%) women had died. The relative risk of mortality, compared to the least active quartile, was as follows: second quartile, 0.95 (95% confidence interval [CI] 0.72 to 1.26); third quartile, 0.63 (95% CI 0.46 to 0.86); most active quartile, 0.67 (95% CI 0.48 to 0.92). The relative risks were not changed by adjustment for cardiac risk factors, chronic obstructive pulmonary disease, or cancer or by excluding all subjects who died in the first 6 years (to eliminate occult disease at baseline). There was no association between activity levels and cardiovascular morbidity or mortality. We conclude that women who were more active lived longer; this effect was not the result of decreased cardiovascular disease.

Does exercise reduce mortality rates in the elderly? experience from the Framingham Heart Study☆

Regular physical activity decreases the mortality rate in middle-aged men and probably in middle-aged women. It is unknown whether this is also true in the elderly. We studied 285 men and women aged 75 years or older who were free of cardiovascular disease. Subjects were ranked by baseline physical activity levels and grouped into quartiles. After adjustments were made for cardiac risk factors, chronic obstructive pulmonary disease, and cancer, women in the second most active quartile had a much lower risk of mortality at 10 years (relative risk 0.24, 95% confidence interval 0.12 to 0.51). There was no statistically significant difference in men. There appeared to be an excess of sudden cardiac deaths in the most active women, although this group still lived longer than the least active women. We conclude that women aged 75 years or older who are more active live longer. This benefit may be attenuated in those who are extremely active.

Does number of children increase the rate of coronary heart disease in men

We examined the association between number of children and coronary heart disease risk among men in two large prospective cohort studies. Data from the Framingham Heart Study comprised a group of 1,632 men who were followed for 30 years; data from the first National Health and Nutrition Examination Survey National Epidemiologic Follow-up Study included 2,584 men who were followed for 3-5 years. We found no relation between number of children and coronary heart disease incidence in these cohorts. This lack of association in men contrasts with the previous positive association found between pregnancy and coronary heart disease in women.

Diet, menopause, and serum cholesterol levels in women: The Framingham Study

Cross-sectional relationships between diet and total serum cholesterol levels were studied in a sample of 428 women from the Framingham Heart Study Cohort, aged 37 to 70 years, from 1957 to 1960. Multiple linear regression was used to control for total calorie intake, systolic blood pressure, physical activity, Metropolitan relative weight, glucose intolerance, and cigarette smoking. There was little evidence for a relationship between total serum cholesterol and dietary fat intake; whereas a marginally significant direct association was found with total fat in postmenopausal women, total and plant fat and cholesterol were inversely associated, and only cholesterol was significant in premenopausal women. A consistent inverse association was observed between total serum cholesterol levels and intake of protein, particularly from plant sources, and a weak inverse association was found with complex carbohydrate intake. Serum cholesterol in women may be influenced by a number of dietary factors and appears to differ according to menopausal status.