Yuxiao Tang

The effect of social networks on the relation between Alzheimer's disease pathology and level of cognitive function in old people: a longitudinal cohort study

BACKGROUND Few data are available about how social networks reduce the risk of cognitive impairment in old age. We aimed to measure this effect using data from a large, longitudinal, epidemiological clinicopathological study. METHODS 89 elderly people without known dementia participating in the Rush Memory and Aging Project underwent annual clinical evaluation. Brain autopsy was done at the time of death. Social network data were obtained by structured interview. Cognitive function tests were Z scored and averaged to yield a global and specific measure of cognitive function. Alzheimers disease pathology was quantified as a global measure based on modified Bielschowsky silver stain. Amyloid load and the density of paired helical filament tau tangles were also quantified with antibody-specific immunostains. We used linear regression to examine the relation of disease pathology scores and social networks to level of cognitive function. FINDINGS Cognitive function was inversely related to all measures of disease pathology, indicating lower function at more severe levels of pathology. Social network size modified the association between pathology and cognitive function (parameter estimate 0.097, SE 0.039, p=0.016, R(2)=0.295). Even at more severe levels of global disease pathology, cognitive function remained higher for participants with larger network sizes. A similar modifying association was observed with tangles (parameter estimate 0.011, SE 0.003, p=0.001, R(2)=0.454). These modifying effects were most pronounced for semantic memory and working memory. Amyloid load did not modify the relation between pathology and network size. The results were unchanged after controlling for cognitive, physical, and social activities, depressive symptoms, or number of chronic diseases. INTERPRETATION These findings suggest that social networks modify the relation of some measures of Alzheimers disease pathology to level of cognitive function.

Frailty is Associated With Incident Alzheimer’s Disease and Cognitive Decline in the Elderly

Objective: To assess the association between frailty and incident Alzheimer’s disease (AD) and cognitive decline. Frailty is common in older persons and associated with adverse health outcomes. Methods: Study subjects included 823 older persons without dementia who participated in the Rush Memory and Aging Project, a longitudinal study of aging, and underwent annual assessments of frailty, cognition, and diagnostic evaluation for AD. Results: During a 3-year follow-up, 89 of 823 participants developed AD. In a proportional hazards model, both baseline level of frailty and annual rate of change in frailty were associated with an increased risk of incident AD. Each additional one tenth of a unit increase on the frailty scale at baseline was associated with >9% increased risk of AD (hazard ratio: 2.44; 95% confidence interval (CI): 1.49, 3.37); each one tenth of a unit increase in annual rate of change in frailty was associated with a 12% increased risk of AD (hazard ratio: 3.30; 95% CI: 1.52, 7.13). These results were unchanged in analyses controlling for vascular risk factors and vascular diseases. Results were similar with a categorical measure of frailty instead of a continuous measure. Further, linear mixed-effects models showed that the level of and rate of change in frailty were also associated with the rate of cognitive decline. Conclusion: Increasing frailty is associated with incident AD and the rate of cognitive decline in older persons. These findings suggest that frailty and AD may share similar etiologies. AD = Alzheimer’s disease; PD = Parkinson’s disease; CI = confidence interval; BMI = body mass index; SD = standard deviation.

Relation of cognitive activity to risk of developing Alzheimer disease

Background: Frequent cognitive activity in old age has been associated with reduced risk of Alzheimer disease (AD), but the basis of the association is uncertain. Methods: More than 700 old people underwent annual clinical evaluations for up to 5 years. At baseline, they rated current and past frequency of cognitive activity with the current activity measure administered annually thereafter. Those who died underwent a uniform postmortem examination of the brain. Amyloid burden, density of tangles, and presence of Lewy bodies were assessed in eight brain regions and the number of chronic cerebral infarctions was noted. Results: During follow-up, 90 people developed AD. More frequent participation in cognitive activity was associated with reduced incidence of AD (HR = 0.58; 95% CI: 0.44, 0.77); a cognitively inactive person (score = 2.2, 10th percentile) was 2.6 times more likely to develop AD than a cognitively active person (score = 4.0, 90th percentile). The association remained after controlling for past cognitive activity, lifespan socioeconomic status, current social and physical activity, and low baseline cognitive function. Frequent cognitive activity was also associated with reduced incidence of mild cognitive impairment and less rapid decline in cognitive function. Among 102 persons who died and had a brain autopsy, neither global nor regionally specific measures of neuropathology were related to level of cognitive activity before the study, at study onset, or during the course of the study. Conclusion: Level of cognitively stimulating activity in old age is related to risk of developing dementia. GLOSSARY: AD = Alzheimer disease; MCI = mild cognitive impairment.

Chronic distress and incidence of mild cognitive impairment

Objective: Mild cognitive impairment (MCI) is associated with increased morbidity and mortality but its development is not well understood. Here we test the hypothesis that chronic psychological distress is associated with increased incidence of MCI in old age. Methods: Participants are older persons from two cohort studies with uniform annual clinical evaluations which included detailed cognitive testing and clinical classification of MCI. We excluded persons with dementia or MCI at baseline; follow-up data were available on 1,256 persons without cognitive impairment (95% of those eligible). At baseline, they completed a six-item measure of neuroticism (mean = 15.6, SD = 6.6), an indicator of the tendency to experience psychological distress. Results: During up to 12 years of follow-up, 482 persons (38%) developed MCI. Risk of MCI increased by about 2% for each one unit increase on the distress scale (relative risk [RR] = 1.02; 95% CI: 1.01, 1.04), with the association slightly stronger in men than women. Overall, a distress-prone person (score = 24, 90th percentile) was about 40% more likely to develop MCI than someone not prone to distress (score = 8, 10th percentile). Adjustment for depressive symptomatology at baseline did not substantially change results (RR = 1.02; 95% CI: 1.00, 1.03). Depressive symptoms were also related to risk of MCI but not after controlling for distress score. In mixed-effects models, higher distress score was associated with lower level of function in multiple cognitive domains at baseline and more rapid cognitive decline, especially in episodic memory. Conclusion: Among older persons without manifest cognitive impairment, higher level of chronic psychological distress is associated with increased incidence of mild cognitive impairment.

Chronic Psychological Distress and Risk of Alzheimer’s Disease in Old Age

Clinical and pathological data from the Rush Memory and Aging Project were used to test the hypothesis that distress proneness is associated with increased risk of Alzheimer’s disease (AD). More than 600 older persons without dementia completed a 6-item measure of neuroticism, a stable indicator of proneness to psychological distress. At annual intervals thereafter, they underwent uniform evaluations that included clinical classification of AD and administration of 18 cognitive tests. Those who died underwent brain autopsy from which composite measures of AD pathology were derived. During a mean of about 3 years of follow-up, 55 people were clinically diagnosed with AD. In analyses that controlled for age, sex, and education, persons with a high level of distress proneness (score = 24, 90th percentile) were 2.7 times more likely to develop AD than those not prone to distress (score = 6, 10th percentile). Adjustment for depressive symptomatology or frequency of cognitive, social, and physical activity did not substantially change this effect. Distress proneness was also associated with more rapid cognitive decline. Among 45 participants who died and underwent brain autopsy, distress proneness was unrelated to diverse measures of AD pathology and was inversely related to cognition after controlling for AD pathology. The results support the hypothesis that distress proneness is associated with increased risk of dementia and suggest that neurobiologic mechanisms other than AD pathology may underlie the association.

The relationship between cerebral Alzheimer’s disease pathology and odour identification in old age

Background: Olfactory dysfunction is common in old age, but its basis is uncertain. Objective: To test the hypothesis that difficulty in identifying odours in old age is related to the accumulation of Alzheimer’s disease pathology. Methods: As part of the Rush Memory and Aging Project, participants completed the 12-item Brief Smell Identification Test, a standard measure of odour identification. During a mean (standred deviation (SD)) of 2.2 (1.2) years of follow-up (range 0.2–4.9), 166 people died, with brain autopsies performed on 129 (77.7%) people and neuropathological examinations completed on 77 (mean (SD) age at death 87.5 (5.9) years; median postmortem interval 6.1 h). From a uniform postmortem examination of multiple brain regions, summary measures of plaque and tangle pathology were derived on the basis of silver staining, and those of amyloid β burden, tangle density and Lewy bodies on the basis of immunohistochemistry. Results: Odour identification performance ranged from 0 to 12 correct (mean (SD) 8.0 (2.6)). In analyses adjusted for age, sex and education, a composite measure of plaques and tangles accounted for >12% of the variation in odour identification. The association remained after controlling for dementia or semantic memory. Density of τ tangles was inversely related to odour identification. A similar effect for amyloid burden was attenuated after controlling for tangles. The association with odour identification was robust for tangles in the entorhinal cortex and CA1/subiculum area of the hippocampus, but not for tangles in other cortical sites. Lewy bodies, identified in 12.5%, were not related to odour identification, probably partly due to to their relative infrequency. Conclusion: The results suggest that difficulty in identifying familiar odours in old age is partly due to the accumulation of neurofibrillar pathology in central olfactory regions.

Odor Identification and Decline in Different Cognitive Domains in Old Age

The authors examined the association of odor identification with rate of decline in different cognitive systems. Participants are 481 older persons from the Rush Memory and Aging Project. At baseline, the Brief Smell Identification Test was administered. At annual intervals for up to 3 years, a battery of 19 cognitive tests was administered from which previously established composite measures of 5 cognitive domains were derived. In mixed-effects models adjusted for age, sex, and education, lower odor identification score was associated with lower function at baseline in each cognitive domain. Lower score was also associated with more rapid decline in perceptual speed (estimate = 0.015, SE = 0.006, p = 0.013) and episodic memory (estimate = 0.012, SE = 0.006, p = 0.030) but not with rate of decline in semantic memory, working memory, or visuospatial ability. Thus, on average, a person with a low odor identification score (6, 10th percentile) declined more than twice as rapidly in perceptual speed and episodic memory as a person with a high score (11, 90th percentile). Results were unchanged in subsequent analyses that controlled for cigarette smoking or clinically diagnosed stroke. The results indicate that impaired odor identification in old age is associated with impaired global cognition and more rapid decline in perceptual processing speed and episodic memory.

Biochemical indicators of vitamin B12 and folate insufficiency and cognitive decline

Background: In some prospective studies, associations of serum vitamin B12 and homocysteine concentrations with cognitive decline have been reported but few have examined the role of methylmalonic acid, a more specific marker of vitamin B12 deficiency than homocysteine. Objective: The aim of the study was to determine whether serum concentrations of vitamin B12 or selected metabolites are related to cognitive decline. Methods: A total of 516 subjects were selected in a stratified random sampling design from among Chicago Health and Aging Project participants for clinical evaluation. We used linear mixed models to examine the association of blood markers of vitamin B12 status to change in cognitive scores over 6 years. Cognitive function was assessed every 3 years and measured as the sum of standardized scores on four tests. Results: Probable vitamin B12 deficiency was observed in 14.2% of the sample. Elevated serum concentrations of homocysteine were present in 19.2% of subjects, and of methylmalonic acid, in 36.4%. Higher serum methylmalonic acid concentrations were predictive of faster rates of cognitive decline (β = −0.00016, SE = 0.0001, p = 0.004) and higher serum vitamin B12 concentrations were associated with slower rates of cognitive decline (β = +0.00013, SE < 0.0001, p = 0.005) in multivariable adjusted mixed models. Serum concentrations of homocysteine had no relationship to cognitive decline. Conclusions: Serum methylmalonic acid and vitamin B12 concentrations may be the more important risk factors for cognitive decline when compared to serum homocysteine concentrations, particularly in older populations exposed to food fortification and possible supplements containing folic acid. CHAP = Chicago Health and Aging Project; CI = confidence interval; FFQ = food frequency questionnaire; NHANES = National Health and Nutrition Examination Survey; OR = odds ratio.

Physical Activity and Leg Strength Predict Decline in Mobility Performance in Older Persons

OBJECTIVES: To assess the extent to which physical activity and leg strength are associated with change in mobility in older persons.

Lower Extremity Motor Function and Disability in Mild Cognitive Impairment

Recent findings suggest that lower extremity motor dysfunction may be a feature of mild cognitive impairment (MCI), but little is known about the nature and significance of lower extremity motor dysfunction in MCI. The aim of this study was to examine the extent to which MCI is associated with impaired gait, balance, and strength and to examine the relation of lower extremity function to disability among persons with MCI in the Rush Memory and Aging Project, a clinical-pathologic study of common chronic conditions of old age. In a series of analyses adjusted for age, sex, and education, individuals with MCI exhibited more impaired gait and balance than individuals without cognitive impairment. Because vascular factors can contribute to lower extremity motor dysfunction, the authors repeated the initial analyses including terms for vascular risk factors and vascular disease, and the associations between MCI and lower extremity motor dysfunction persisted. Moreover, among those with MCI, impairments in gait and balance were associated with an increased likelihood of disability. These findings suggest that lower extremity motor dysfunction is common and contributes to disability in MCI, but lower extremity motor dysfunction in MCI does not appear to be explained by the vascular factors examined in this study.