Lisa L. Barnes

Natural history of mild cognitive impairment in older persons

Background Cognitive abilities of older persons range from normal, to mild cognitive impairment, to dementia. Few large longitudinal studies have compared the natural history of mild cognitive impairment with similar persons without cognitive impairment. Methods Participants were older Catholic clergy without dementia, 211 with mild cognitive impairment and 587 without cognitive impairment, who underwent annual clinical evaluation for AD and an assessment of different cognitive abilities. Cognitive performance tests were summarized to yield a composite measure of global cognitive function and separate summary measures of episodic memory, semantic memory, working memory, perceptual speed, and visuospatial ability. The authors compared the risk of death, risk of incident AD, and rates of change in global cognition and different cognitive domains among persons with mild cognitive impairment to those without cognitive impairment. All models controlled for age, sex, and education. Results On average, persons with mild cognitive impairment had significantly lower scores at baseline in all cognitive domains. Over an average of 4.5 years of follow-up, 30% of persons with mild cognitive impairment died, a rate 1.7 times higher than those without cognitive impairment (95% CI, 1.2 to 2.5). In addition, 64 (34%) persons with mild cognitive impairment developed AD, a rate 3.1 times higher than those without cognitive impairment (95% CI, 2.1 to 4.5). Finally, persons with mild cognitive impairment declined significantly faster on measures of episodic memory, semantic memory, and perceptual speed, but not on measures of working memory or visuospatial ability, as compared with persons without cognitive impairment. Conclusions Mild cognitive impairment is associated with an increased risk of death and incident AD, and a greater rate of decline in selected cognitive abilities.

Individual differences in rates of change in cognitive abilities of older persons.

The authors examined change in cognitive abilities in older Catholic clergy members. For up to 6 years, participants underwent annual clinical evaluations, which included a battery of tests from which summary measures of 7 abilities were derived. On average, decline occurred in each ability and was more rapid in older persons than in younger persons. However, wide individual differences were evident at all ages. Rate of change in a given domain was not strongly related to baseline level of function in that domain but was moderately associated with rates of change in other cognitive domains. The results suggest that change in cognitive function in old age primarily reflects person-specific factors rather than an inevitable developmental process.

Education modifies the relation of AD pathology to level of cognitive function in older persons

Objective: To test the hypothesis that years of formal education modifies the relation of AD pathology to level of cognitive function. Methods: A total of 130 older Catholic clergy participating in the Religious Orders Study underwent annual cognitive function testing and brain autopsy at the time of death. Individual cognitive function tests were z-scored and averaged to yield a global measure of cognitive function and summary measures of five different cognitive abilities. Neuritic and diffuse plaques and neurofibrillary tangles were counted in separate 1 mm2 areas of maximal density. Counts were converted to standard scores by dividing by their SD, and combined to yield a global AD pathology score and summary scores of each postmortem index. Linear regression was used to examine the relation of education and AD pathology scores to level of cognitive function proximate to death, controlling for age and sex. Subsequent analyses tested the interaction between education and each AD pathology score to determine whether education modified the relation of AD pathology to level of cognitive function. Additional analyses examined these associations on five specific cognitive abilities. Results: Both years of formal education (regression coefficient = 0.073, p = 0.0001) and the global AD pathology score (regression coefficient = −0.689, p < 0.0001) were related to level of cognitive function. When an interaction term between education and AD pathology was added to the model, the association between a unit of AD pathology and level of cognitive function was 0.088 (p = 0.0078) standard unit less for each year of education than the level predicted from the model without the interaction term. Whereas neuritic plaques, diffuse plaques, and neurofibrillary tangles were all strongly related to cognitive function, education only modified the relation of neuritic plaques (p = 0.002) and diffuse plaques (p = 0.03) to cognition, but not neurofibrillary tangles. In analyses examining five different cognitive abilities, the interaction between education and the neuritic plaque score was strongest for perceptual speed and weakest for episodic memory. Conclusions: These data provide strong evidence that the relation between senile plaques and level of cognitive function differs by years of formal education.

Depressive symptoms, cognitive decline, and risk of AD in older persons

Background:Cross-sectional and retrospective case-control studies suggest an association of depression symptoms with cognitive impairment and AD, but there have been few prospective studies and their results have been inconsistent. Methods:Participants are Catholic clergy members who were aged ≥65 years and who did not have clinical evidence of AD. During a 7-year period, they underwent annual clinical evaluations that included clinical classification of AD and detailed cognitive function testing from which global and specific measures of cognition were derived. Number of depressive symptoms was assessed at baseline with a modified, 10-item Center for Epidemiologic Studies Depression Scale (CES-D). The association of CES-D score with incident AD, using proportional hazards models, and cognitive decline, using random effects models, was examined. Results:At baseline, participants reported an average of about one depressive symptom on the CES-D scale (range, 0 to 8). During the 7 years of follow-up, 108 persons developed AD. In analyses that controlled for selected demographic and clinical variables including baseline level of cognitive function, CES-D score was associated with both risk of AD and rate of cognitive decline. For each depressive symptom, risk of developing AD increased by an average of 19%, and annual decline on a global cognitive measure increased by an average of 24%. Conclusions:The results raise the possibility that depressive symptoms in older persons may be associated with risk of developing AD.

Social resources and cognitive decline in a population of older African Americans and whites

Objective: To examine the relation of social resources and cognitive decline in older adults. Methods: Data are from the Chicago Health and Aging Project, an epidemiologic study of risk factors for Alzheimer disease (AD) and other common conditions in a geographically defined population of older persons. The sample consisted of 6,102 non-Hispanic African Americans (61.2%) and whites, aged ≥ 65, who underwent up to three interviews during an average of 5.3 years of follow-up. Each interview included administration of four cognitive function tests from which a composite measure of cognition was formed. Social networks were based on the number of children, relatives, and friends seen at least once a month. Social engagement was measured with four items related to social and productive activity. Results: Higher number of social networks and level of social engagement were positively correlated with initial level of cognitive function (networks estimate = 0.003, engagement estimate = 0.060, both p < 0.001). Both resources were also associated with a reduced rate of cognitive decline. A high (90th percentile) number of networks reduced the rate of decline by 39% compared to a low level (10th percentile), and high social engagement reduced decline by 91%. These relations remained after controlling for socioeconomic status, cognitive activity, physical activity, depressive symptoms, and chronic medical conditions. Conclusions: Greater social resources, as defined by social networks and social engagement, are associated with reduced cognitive decline in old age.

Overview and Findings from the Rush Memory and Aging Project

The Memory and Aging Project is a longitudinal, epidemiologic clinical-pathologic cohort study of common chronic conditions of aging with an emphasis on decline in cognitive and motor function and risk of Alzheimers disease (AD). In this manuscript, we first summarize the study design and methods. Then, we present data on: (1) the relation of motor function to cognition, disability, and death; (2) the relation of risk factors to cognitive and motor outcomes, disability and death; (3) the relation of neuropathologic indices to cognitive outcomes; (4) the relation of risk factors to neuropathologic indices; and (5) additional study findings. The findings are discussed and contextualized.

Assessment of lifetime participation in cognitively stimulating activities.

Cognitively stimulating experience is thought to contribute to cognitive reserve. We constructed a questionnaire consisting of 25 items about frequency of participation in cognitive activities across the life span and administered it to two groups of older persons. The total score on the scale had high internal consistency (coefficient alpha 1/4 0.88) and temporal stability over a 4-week re-test interval (r =.79), and it was positively correlated with education. In analyses controlling for age, sex, and education, more frequent cognitive activity was related to better perceptual speed, visuospatial ability, and semantic memory but not to episodic memory or working memory. The results suggest that the scale provides a psychometrically sound measure of frequency of cognitive activity across the life span.

Early and late life cognitive activity and cognitive systems in old age.

Little is known about the relative benefits of cognitively stimulating activities at different points in the lifespan. In a cohort of 576 older persons without dementia, we assessed current and past (childhood, young adulthood, middle age) frequency of cognitive activity; availability of cognitively stimulating resources in the home in childhood and middle age; and 5 domains of cognitive function. Past cognitive activity and cognitive resources were positively correlated with both current cognitive activity and current cognitive function. The association with cognitive function was reduced after controlling for current cognitive activity, however. Current cognitive activity was associated with better cognitive function, especially semantic memory and perceptual speed, even after controlling for past activity. The results suggest that past cognitive activity contributes to current cognition principally through its association with cognitive activity in old age.

Purpose in Life Is Associated With Mortality Among Community-Dwelling Older Persons

Objective: To assess the association between purpose in life and all-cause mortality in community-dwelling elderly persons. Methods: We used data from 1238 older persons without dementia from two longitudinal cohort studies (Rush Memory and Aging Project and Minority Aging Research Study) with baseline evaluations of purpose in life and up to 5 years of follow-up to test the hypothesis that greater purpose in life is associated with a reduced risk of mortality among community-dwelling older persons. Results: The mean ± standard deviation score on the purpose in life measure at baseline was 3.7 ± 0.5 (range = 2–5), with higher scores indicating greater purpose in life. During the 5-year follow-up (mean = 2.7 years), 151 of 1238 persons (12.2%) died. In a proportional hazards model adjusted for age, sex, education, and race, a higher level of purpose in life was associated with a substantially reduced risk of mortality (hazard ratio = 0.60, 95% Confidence Interval = 0.42, 0.87). Thus, the hazard rate for a person with a high score on the purpose in life measure (score = 4.2, 90th percentile) was about 57% of the hazard rate of a person with a low score (score = 3.1, 10th percentile). The association of purpose in life with mortality did not differ among men and women or whites and blacks. Further, the finding persisted after the addition of terms for several potential confounders, including depressive symptoms, disability, neuroticism, the number of chronic medical conditions, and income. Conclusion: Greater purpose in life is associated with a reduced risk of all-cause mortality among community-dwelling older persons. MAP = Memory and Aging Project; MARS = Minority Aging Research Study; CES-D = Center for Epidemiologic Studies Depression scale.

Late-Life Social Activity and Cognitive Decline in Old Age

We examined the association of social activity with cognitive decline in 1138 persons without dementia at baseline with a mean age of 79.6 (SD = 7.5) who were followed for up to 12 years (mean = 5.2; SD = 2.8). Using mixed models adjusted for age, sex, education, race, social network size, depression, chronic conditions, disability, neuroticism, extraversion, cognitive activity, and physical activity, more social activity was associated with less cognitive decline during average follow-up of 5.2 years (SD = 2.7). A one point increase in social activity score (range = 1-4.2; mean = 2.6; SD = 0.6) was associated with a 47% decrease in the rate of decline in global cognitive function (p < .001). The rate of global cognitive decline was reduced by an average of 70% in persons who were frequently socially active (score = 3.33, 90th percentile) compared to persons who were infrequently socially active (score = 1.83, 10th percentile). This association was similar across five domains of cognitive function. Sensitivity analyses revealed that individuals with the lowest levels of cognition or with mild cognitive impairment at baseline did not drive this relationship. These results confirm that more socially active older adults experience less cognitive decline in old age.