Statin Initiation and Risk of Incident Alzheimer Disease and Cognitive Decline in Genetically Susceptible Older Adults.

BACKGROUND AND OBJECTIVES: The association of statin initiation with incident Alzheimer disease (AD) dementia and cognitive decline by the APOE ε4 allele is unknown. Our objective was to examine whether the association of statin initiation with incident AD dementia and cognitive decline differs by the APOE ε4 allele. METHODS: This population-based longitudinal cohort study was conducted in 4 urban communities in Chicago, IL, United States, consisting of 4,807 participants. Statin initiation is based on the inspection of medications during home assessments. Clinical diagnosis for incident AD used the NINCDS-ADRDA criteria, and longitudinal measurements of global cognition consisted of episodic memory, perceptual speed, and the Mini-Mental State Examination tests. RESULTS: The study participants had a mean age of 72 years, consisting of 63% female individuals and 61% non-Hispanic Black individuals. During the study period, 1,470 (31%) participants reported statin initiation. In a covariate-adjusted competing risk model, statin initiation was associated with a reduced risk of incident clinical AD [hazard ratio (HR) 0.81 (95% CI 0.70-0.94)] compared with nonusers. This association was statistically significantly lower (p interaction = 0.015) among participants with the APOE ε4 allele [HR 0.60 (95% CI 0.49-0.74)] compared with those without the APOE ε4 allele [HR 0.96 (95% CI 0.82-1.12)]. The annual decline in global cognition (ß = 0.021, 95% CI 0.007-0.034) and episodic memory (ß = 0.020, 95% CI 0.007-0.033) was also substantially slower among participants with the APOE ε4 allele after statin initiation compared with nonusers. However, the association of statin initiation with cognitive decline was not significant among those without the APOE ε4 allele. DISCUSSION: Our findings suggest that statins might be associated with a lower risk of incident AD among individuals with the APOE ε4 allele. The benefits of statin therapy need further consideration in randomized clinical trials, especially among those with the APOE ε4 allele. CLASSIFICATION OF EVIDENCE: This study provides Class II evidence that among those aged 65 years or older, statin initiation was associated with a reduced risk of Alzheimer disease, especially in the presence of an APOE-e4 allele.

Cardiovascular health and cognitive outcomes: Findings from a biracial population-based study in the United States.

INTRODUCTION: The aim of this study was to evaluate the association of cardiovascular health (CVH) with cognitive outcomes, including incident Alzheimer's dementia, rate of cognitive decline, and measures of brain injury and structure. METHODS: This study consisted of 1702 Black or African American and White participants living in the south side of Chicago, Illinois, and enrolled in the Chicago Health and Aging Project, a population-based cohort since 1993. CVH was based on seven risk factors, including diet, physical activity, body mass index, smoking, dyslipidemia, hypertension, and diabetes. RESULTS: In a multivariable-adjusted model, CVH was associated with a lower risk of Alzheimer's dementia. The hazard ratio per 1 additional point in CVH score was 0.84 (95% CI 0.76, 0.94). CVH was also associated with a slower rate of cognitive decline and less volume (injury) in white matter hyperintensities. DISCUSSION: Promoting CVH in communities with Black residents may lower the future risk of Alzheimer's dementia.

Serum neurofilament light chain, brain infarcts, and the risk of stroke: a prospective population-based cohort study.

Neurofilament light chain (NfL), a neuron-specific protein, has been related to several neurodegenerative diseases. In addition, elevated levels of NfL have also been observed in patients admitted to the hospital for stroke, suggesting that NfL as a biomarker may extend well beyond neurodegenerative diseases. Therefore, using data from the Chicago Health and Aging Project (CHAP), a population-based cohort study, we prospectively investigated the association of serum NfL levels with incident stroke and brain infarcts. During a follow-up of 3603 person-years, 133 (16.3%) individuals developed incident stroke, including ischemic and hemorrhagic. The HR (95%CI) of incident stroke was 1.28 (95%CI 1.10-1.50) per 1 standard deviation (SD) increase of log10 NfL serum levels. Compared to participants in the first tertile of NfL (i.e., lower levels), the risk of stroke was 1.68 times higher (95%CI 1.07-2.65) in those in the second tertile and 2.35 times higher (95%CI 1.45-3.81) in those in the third tertile of NfL. NfL levels were also positively associated with brain infarcts; 1-SD in log10 NfL levels was associated with 1.32 (95%CI 1.06-1.66) higher odds of one or more brain infarcts. These results suggest that NfL may serve as a biomarker of stroke in older adults.

Vitamin D intake and cognitive decline in Blacks and Whites: The role of diet and supplements.

INTRODUCTION: To determine the role of vitamin D intake on cognitive decline among Blacks and Whites. METHODS: Using data from the population-based Chicago Health and Aging Project, we studied 2061 Blacks and 1329 Whites with dietary vitamin D data and cognitive testing over 12 years of follow-up. Multivariable linear mixed-effects models were used to determine the association of vitamin D intake with cognitive decline. RESULTS: Vitamin D intake, particularly dietary vitamin D, was associated with a slower rate of decline in cognitive function among Blacks. In Blacks, comparing individuals in the lowest tertile of dietary intake, those in the highest tertile had a slower cognitive decline of 0.017 units/year (95% confidence interval 0.006, 0.027), independently of supplementation use. In Whites, vitamin D intake was not associated with cognitive decline. DISCUSSION: Dietary vitamin D may help to slow the decline in cognitive abilities among Blacks as they age.

White matter hyperintensity, neurofilament light chain, and cognitive decline.

OBJECTIVE: We aimed to determine whether combining white matter hyperintensity (WMH) with neurofilament light chain (NfL) could provide additional information for cognition in older adults. METHODS: Utilizing data from the population-based Chicago Health and Aging Project, we studied 701 individuals with both biomarkers and cognitive data during the follow-up period. NfL was measured using an ultrasensitive immunoassay, single-molecule array technology. MRI scans of the brain were acquired using 1.5-T systems. Global cognitive function was created as a composite measure of four neuropsychological tests, standardized and averaged to z-scores. Multivariable linear mixed-effects models were used to evaluate the association of WMH and NfL with the rate of cognitive decline. RESULTS: Higher WMH and NfL were associated with a faster rate of cognitive decline during the follow-up; ß -coefficients (95%CIs) were -0.011 (-0.02, -0.001) and -0.010 (-0.017, -0.003), respectively. In individuals with lower concentration of NfL (i.e., bottom tertile), a higher WMH volume was associated with a faster cognitive decline ( ß : -0.030; 95%CI -0.046, -0.014). Similarly, in individuals with lower volumes of WMH (i.e., bottom tertile), a higher concentrations of NfL was associated with a faster cognitive decline ( ß : -0.023; 95%CI -0.042, -0.005). When we combined WMH with NfL, we noted a graded association with increasing volumes of WMH, particularly in people with lower NfL values. INTERPRETATION: While both biomarkers, WMH and NfL, were similarly associated with the annual rate of cognitive decline, our study suggests that they provide different underlying mechanisms affecting cognition.

Lifestyle and Cognitive Decline in Community-Dwelling Stroke Survivors.

BACKGROUND: Patients with stroke are at a higher risk of cognitive impairment and Alzheimer's disease dementia. OBJECTIVE: To quantify the role of lifestyle pre-stroke, post-stroke, and changes in lifestyle before and after stroke with cognitive decline in community-dwelling stroke survivors. METHODS: Utilizing data from the Chicago Health and Aging Project, a population-based cohort study, we studied 1,078 individuals with stroke (662 incident and 416 prevalent) who underwent cognitive testing during the study period. A healthy lifestyle score was defined by scoring four behaviors: non-smoking, exercising, being cognitively active, and having a high-quality diet. The global cognitive score was derived from a comprehensive battery of 4 standardized tests. RESULTS: The mean age at incident stroke was 78.2 years, and 60.1% were women. A healthy lifestyle pre-incident stroke was associated with a slower rate of cognitive decline after stroke. Participants with 3-4 healthy lifestyle factors pre-incident stroke had a slower cognitive decline after stroke by 0.046 units/year (95% CI 0.010, 0.083), or 47.7% slower, than participants with 0-1 healthy lifestyle factor. Lifestyle score post-prevalent stroke was not associated with cognitive decline. Changes in lifestyle behaviors from pre- to post-incident stroke were related to cognitive decline after stroke. Individuals who deteriorated their lifestyle quality after stroke had a faster cognitive decline by 0.051 units/year (ß -0.051, 95% CI -0.090, -0.012) than participants with no change in lifestyle score. CONCLUSION: A healthy lifestyle pre-stroke was associated with a slower rate of cognitive decline in stroke survivors, highlighting the importance of primary prevention. After the stroke, changes in lifestyle behaviors may influence the cognitive abilities of older adults as they age.

Association of Subjective Memory Complaints With White Matter Hyperintensities and Cognitive Decline Among Older Adults in Chicago, Illinois.

Importance: Subjective memory complaints (SMCs) are associated with a faster cognitive decline; whether this association is also associated with structural brain alterations, such as white matter hyperintensity (WMH) volumes, requires investigation. Objective: To evaluate the association of SMCs with WMH volumes and cognitive decline and investigate the role of WMH volumes in the association between SMCs and cognitive decline. Design, Setting, and Participants: The Chicago Health and Aging Project, a population-based cohort study, enrolled adults aged 65 years or older. Data collection occurred in 3-year cycles from 1993 until 2012. Our study comprised 975 participants with magnetic resonance imaging assessments, of which 900 participants had data on SMCs and covariates, and 713 participants provided 2 or more cognitive assessments during the follow-up. Statistical analyses were conducted from May to October 2021. Exposures: SMCs were obtained from self-reported questionnaire data during clinical evaluations, and the cycle, when reported, constituted the baseline of our study. Based on the frequency and severity of concerns, we categorized participants into 3 groups, (1) no concerns, (2) moderate concerns, and (3) very worried. Main Outcomes and Measures: Volumetric magnetic resonance imaging measures of WMH volume and neuropsychological testing assessments of global cognition. Linear regression analysis was used to investigate the association between SMCs and WMH volumes in a multivariable model adjusted for age, sex, race and ethnicity, education, APOE4 status, and total intracranial volume. The association of SMCs with cognitive decline was investigated using linear mixed-effects models for age, sex, race and ethnicity, education, APOE4 status, follow-up time, and each variable in interaction with time to estimate the annual longitudinal change in cognitive function. Results: Of the 900 participants with data on SMCs, covariates, and WMH volumes, 553 (61.4%) were women, 539 (59.9%) were African American, and the mean (SD) age was 79.5 (6.2) years. SMCs were associated with a larger WMH volume and faster cognitive decline. Compared with participants with no concerns, participants who were very worried had higher WMH volumes (ß = 0.833; 95% CI, 0.203-1.463) and 174% faster cognitive decline (ß = -0.049; 95% CI, -0.076 to -0.022). The association between SMCs and cognitive decline remained statistically significant among individuals with large WMH volumes (ie, within the fourth quartile). Within the fourth quartile of WMH volumes, participants who were very worried had 428% faster cognitive decline (ß = -0.077; 95% CI, -0.144 to -0.011) compared with participants with no concerns. Conclusions and Relevance: This cohort study suggests that SMCs, frequently reported by older individuals, are an important sign of cognitive impairment, especially among people with abnormalities in brain structure, such as larger WMH volumes.

Healthy lifestyle and life expectancy with and without Alzheimer's dementia: population based cohort study.

OBJECTIVE: To determine the impact of lifestyle factors on life expectancy lived with and without Alzheimer's dementia. DESIGN: Prospective cohort study. SETTING: The Chicago Health and Aging Project, a population based cohort study in the United States. PARTICIPANTS: 2449 men and women aged 65 years and older. MAIN EXPOSURE: A healthy lifestyle score was developed based on five modifiable lifestyle factors: a diet for brain health (Mediterranean-DASH Diet Intervention for Neurodegenerative Delay-MIND diet score in upper 40% of cohort distribution), late life cognitive activities (composite score in upper 40%), moderate or vigorous physical activity (≥150 min/week), no smoking, and light to moderate alcohol consumption (women 1-15 g/day; men 1-30 g/day). MAIN OUTCOME: Life expectancy with and without Alzheimer's dementia in women and men. RESULTS: Women aged 65 with four or five healthy factors had a life expectancy of 24.2 years (95% confidence interval 22.8 to 25.5) and lived 3.1 years longer than women aged 65 with zero or one healthy factor (life expectancy 21.1 years, 19.5 to 22.4). Of the total life expectancy at age 65, women with four or five healthy factors spent 10.8% (2.6 years, 2.0 to 3.3) of their remaining years with Alzheimer's dementia, whereas women with zero or one healthy factor spent 19.3% (4.1 years, 3.2 to 5.1) with the disease. Life expectancy for women aged 65 without Alzheimer's dementia and four or five healthy factors was 21.5 years (20.0 to 22.7), and for those with zero or one healthy factor it was 17.0 years (15.5 to 18.3). Men aged 65 with four or five healthy factors had a total life expectancy of 23.1 years (21.4 to 25.6), which is 5.7 years longer than men aged 65 with zero or one healthy factor (life expectancy 17.4 years, 15.8 to 20.1). Of the total life expectancy at age 65, men with four or five healthy factors spent 6.1% (1.4 years, 0.3 to 2.0) of their remaining years with Alzheimer's dementia, and those with zero or one healthy factor spent 12.0% (2.1 years, 0.2 to 3.0) with the disease. Life expectancy for men aged 65 without Alzheimer's dementia and four or five healthy factors was 21.7 years (19.7 to 24.9), and for those with zero or one healthy factor life expectancy was 15.3 years (13.4 to 19.1). CONCLUSION: A healthy lifestyle was associated with a longer life expectancy among men and women, and they lived a larger proportion of their remaining years without Alzheimer's dementia. The life expectancy estimates might help health professionals, policy makers, and stakeholders to plan future healthcare services, costs, and needs.