Objective

To characterize the course of cognitive decline during the prodromal phase of Alzheimer's disease.

Design

Longitudinal cohort study with up to 16 years of observation.

Participants

Older persons from two projects underwent annual clinical evaluations that included cognitive function testing and clinical classification of mild cognitive impairment, dementia, and Alzheimer's disease. At baseline, there were 2,071 individuals without dementia and 1,511 without cognitive impairment.

Main Outcome Measures

Change in previously established composite measures of global cognition and specific cognitive domains assessed in mixed-effects models that allow rate of decline to shift at specific points.

Results

During follow-up, 462 persons developed Alzheimer's disease (20 with dementia solely due to another condition were excluded). Five to six years before the diagnosis, rate of global cognitive decline sharply accelerated by more than 15-fold. The acceleration in decline occurred slightly earlier for semantic memory (76 months before diagnosis) and working memory (75 months) than other cognitive functions. Mild cognitive impairment was also preceded by years of cognitive decline which began earlier (80 months before diagnosis) and proceeded more rapidly (annual loss of 0.102 unit) in the amnestic than nonamnestic (62 months, 0.072 unit) subtype.

Conclusion

Dementia due to Alzheimer's disease is preceded by about five to six years of accelerated decline in multiple cognitive functions. By contrast, little decline is evident in persons not developing Alzheimer's disease.

Context

Administration of cognitive test batteries by telephone has been shown to be a valid and cost-effective means of assessing cognition, but it remains relatively uncommon in epidemiological research.

Objective

To develop composite cognitive measures and assess how much of the variability in their scores is associated with mode of test administration (i.e., in person or by telephone).

Design

Cross-sectional cohort study

Setting

Late Onset of Alzheimer’s Disease Family Study conducted at 18 centers across the United States.

Participants

A total of 1,584 persons, 368 with dementia, from 646 families.

Main Outcome Measures

Scores on composite measures of memory and cognitive function derived from a battery of 7 performance tests administered in person (69%) or by telephone (31%) by examiners who underwent a structured performance-based training program with annual recertification.

Results

Based in part on the results of a factor analysis of the 7 tests, we developed summary measures of working memory, declarative memory, episodic memory, semantic memory, and global cognition. In linear regression analyses, mode of test administration accounted for less than 2% of the variance in the measures. In mixed-effects models, variability in cognitive scores due to center was small relative to variability due to differences between individuals and families.

Conclusions

In epidemiologic research on aging and AD, assessment of cognition by telephone has little effect on performance and provides operational flexibility and a means of reducing costs and missing data.

Background

White matter hyperintensity volume (WMHV), cerebral infarcts, and total brain volume (TBV) are associated with cognitive function, but few studies have examined these associations in the general population or whether they differ by race.

Objective

To examine the association of WMHV, cerebral infarcts, and TBV with global cognition and cognition in 5 separate domains in a biracial population sample.

Setting

A biracial community population of Chicago, Illinois.

Design

Cross-sectional population study.

Participants

The study population comprised 575 participants from the Chicago Health and Aging Project (CHAP).

Main Outcome Measures

Volumetric magnetic resonance imaging (MRI) measures of WMHV, TBV, and cerebral infarcts and detailed neuropsychological testing assessments of global cognition and 5 cognitive domains.

Results

Overall and among those without dementia, cognition was inversely associated with WMHV and number of infarcts but was positively associated with TBV. When all 3 measures were simultaneously added to the model, the association of global cognition with WMHV and TBV remained significant and unchanged but was no longer significant with infarcts. Among subjects without dementia, all 3 MRI measures were associated with performance in multiple cognitive domains, specifically perceptual speed. However, among subjects with dementia, only TBV was associated with cognition and performance in multiple cognitive systems. Race did not significantly modify any of these associations.

Conclusions

In this biracial general population sample, the associations of MRI measures with cognition differed according to clinical status of subjects (stronger among subjects without dementia) and were not modified by race. These associations did not affect all cognitive domains equally but were more consistent with impairments in perceptual speed.

Objective

Loss of muscle strength is common and associated with a variety of adverse health outcomes in old age, but few studies have examined the association of muscle strength with the risk of Alzheimer’s disease (AD) or mild cognitive impairment (MCI). We tested the hypothesis that muscle strength is associated with incident AD and MCI.

Design

Prospective, observational cohort study.

Setting

Retirement communities across the Chicago metropolitan area.

Participants

More than 900 community-based older persons without dementia at the baseline evaluation and in whom strength was measured in nine muscle groups in both arms and legs as well as in the axial muscles and summarized into a composite measure of muscle strength.

Main Outcome Measures

Incident AD, MCI and rate of change in global cognitive function.

Results

During a mean follow-up of 3.6 years, 138 persons developed AD. In a proportional hazards model adjusted for age, sex, and education, each 1 unit increase in muscle strength at baseline was associated with about a 43% decrease in the risk of AD (HR, 0.57; 95% CI, 0.41,0.79). The association of muscle strength with AD persisted even after adjustment for several covariates, including body mass index, physical activity, pulmonary function, vascular risk factors, vascular diseases and apolipoprotein E4 status. Further, in a mixed-effects model adjusted for age, sex, education, and baseline level of global cognition, increased muscle strength was associated with a slower rate of decline in global cognitive function (p<0.001). Finally, muscle strength was associated with a decreased risk of MCI, the precursor to AD (HR, 0.67; 95% CI, 0.54, 0.84).

Conclusion

These findings suggest a link between muscle strength, AD and cognitive decline in older persons.

Objective

To assess mortality associated with mild cognitive impairment (MCI) and Alzheimer's disease (AD) in older African Americans and whites from an urban community.

Design

Longitudinal population-based observational study.

Setting

Four adjacent neighborhoods of Chicago, IL.

Participants

1,715 persons deemed free of dementia in a previous wave of data collection and sampled for detailed clinical evaluation: 802 had no cognitive impairment, 597 had MCI, 296 had AD, and 20 had other forms of dementia.

Main Outcome Measure

All-cause mortality.

Results

During up to 10 years of observation (mean = 4.7, SD = 3.0), 634 individuals died (37%). Compared to people without cognitive impairment, risk of death was increased by about 50% in those with MCI (hazard ratio [HR] = 1.48; 95% confidence interval [CI]: 1.22, 1.80) and was nearly threefold greater in those with AD (HR = 2.84; 95% CI:2.29, 3.52). These effects were seen in both African Americans and whites and did not differ by race. In MCI, risk of death increased with increasing severity of cognitive impairment and this effect did not vary by race. A similar effect was seen in AD, but it was slightly stronger for black than white persons. In both MCI and AD, the association of cognitive impairment with survival was stronger for perceptual speed than for other cognitive functions.

Conclusion

The presence and severity of MCI and AD are associated with reduced survival in African Americans and these effects are comparable to those seen in white persons.