Background

Cross-sectional studies suggest that low 25-hydroxyvitamin D (25[OH]D) may be a risk factor for depression; however, there are few prospective studies. We examined the association between 25(OH)D and depressive symptoms in community-dwelling persons aged 70-79 years in the Health, Aging, and Body Composition (Health ABC) Study (n = 2598).

Methods

Depressive symptoms were assessed using the Center for Epidemiologic Studies-Depression Scale (CES-D) at baseline and 2-, 3- and 4-year follow-up. Serum 25(OH)D was measured at 1-year follow-up and categorized as <20, 20-<30, and ≥30 ng/mL. Mixed models were used to examine change in CES-D scores according to 25(OH)D categories. The association between 25(OH)D categories and incident depression (CES-D short score ≥10 or antidepressant medication use) were assessed using Cox proportional hazards models. Analyses were adjusted for socio-demographic and behavioral characteristics, season, and chronic conditions.

Results

Thirty-three percent of participants had 25(OH)D <20ng/mL. Serum 25(OH)D was not associated with CES-D scores at baseline (p = .51); however, CES-D scores increased over time and were significantly associated with 25(OH)D at 2-year (p = .003) and 4-year follow-up (p < .001). Among 2,156 participants free of depression at the 1-year follow-up, the cumulative incidence of depression was 26.9%. Participants with 25(OH)D <20ng/mL were at greater risk of developing depression (HR [95% CI]: 1.65 [1.23-2.22]) over 4 years of follow-up compared with those with 25(OH)D ≥30ng/mL.

Conclusion

Low 25(OH)D was independently associated with a greater increase in depressive symptom scores and incident depression in community-dwelling older adults.

Background and purpose

Arterial stiffness is a measure of subclinical cardiovascular disease and increases with age. This study examines the association between arterial stiffness and cognitive decline in a cohort of older adults.

Methods

A total of 2488 subjects with baseline measure of arterial stiffness (mean age, 74.2 years; 52.3% women) were prospectively followed over 9 years in the Health, Aging, and Body Composition Study. Arterial stiffness was measured as pulse wave velocity (PWV) and analyzed in tertiles. Cognitive function was assessed using the Modified Mini-Mental State examination at baseline and repeated at years 3, 5, 8, and 10. Lower Modified Mini-Mental State examination scores indicate worse function. We fit linear mixed models to examine longitudinal changes in cognitive function over the 9 years of follow-up and logistic regression models, restricted to 1331 participants, to examine cognitive impairment defined as a decrease of ≥5 points after 9 years. We adjusted for sociodemographics, Apoe4, and cardiovascular disease risk factors.

Results

The annual decrease in Modified Mini-Mental State examination scores was 0.30 points at low PWV (95% confidence interval [CI], -0.37 to -0.22), 0.46 points at middle PWV (95% CI, -0.54 to -0.39), and 0.45 points at high PWV (95% CI, -0.53 to -0.38), from fully adjusted linear mixed models. In fully adjusted models, the odds of cognitive impairment after 9 years of follow-up was 40% greater for subjects with middle PWV (odds ratio [OR], 1.40; 95% CI, 1.03-1.92) and 59% greater for subjects with high PWV (OR, 1.59; 95% CI, 1.16-2.18), compared with low PWV.

Conclusions

High arterial stiffness was modestly associated with cognitive decline and impairment. Interventions to prevent arterial stiffness may be effective in delaying cognitive decline.

Importance

Apolipoprotein E (APOE) ε4 is an established risk factor for cognitive decline and the development of dementia, but other factors may help to minimize its effects.

Objective

Using APOE ε4 as an indicator of high risk, we investigated factors associated with cognitive resilience among black and white older adults who are APOE ε4 carriers.

Design, setting, and participants

Participants included 2487 community-dwelling older (aged 69-80 years at baseline) black and white adults examined at 2 community clinics in the prospective cohort Health, Aging, and Body Composition (Health ABC) study. The baseline visits occurred from May 1997 through June 1998. Our primary analytic cohort consisted of 670 APOE ε4 carriers (329 black and 341 white participants) who were free of cognitive impairment at baseline and underwent repeated cognitive testing during an 11-year follow-up (through 2008) using the Modified Mini-Mental State Examination.

Main outcomes and measures

We stratified all analyses by race. Using the Modified Mini-Mental State Examination scores, we assessed normative cognitive change in the entire cohort (n = 2487) and classified the APOE ε4 carriers as being cognitively resilient vs nonresilient by comparing their cognitive trajectories with those of the entire cohort. We then conducted bivariate analyses and multivariable random forest and logistic regression analyses to explore factors predictive of cognitive resilience in APOE ε4 carriers.

Results

Among white APOE ε4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, no recent negative life events, a higher literacy level, advanced age, a higher educational level, and more time spent reading. Among black APOE ε4 carriers, the strongest predictors of cognitive resilience were, in relative order of importance, a higher literacy level, a higher educational level, female sex, and the absence of diabetes mellitus. In follow-up logistic regression models, higher literacy level (adjusted odds ratio [OR], 9.50 [95% CI, 2.67-60.89]), a higher educational level (adjusted OR for college graduate vs less than high school, 3.81 [95% CI, 1.13-17.56]), and age (adjusted OR for 73-76 vs 69-72 years, 2.01 [95% CI, 1.13-3.63]) had significant independent effects in predicting cognitive resilience among white APOE ε4 carriers. Among black APOE ε4 carriers, a higher literacy level (adjusted OR, 2.27 [95% CI, 1.29-4.06]) and a higher educational level (adjusted OR for high school graduate/some college vs less than high school, 2.86 [95% CI, 1.54-5.49]; adjusted OR for college graduate vs less than high school, 2.52 [95% CI, 1.14-5.62]) had significant independent effects in predicting cognitive resilience.

Conclusions and relevance

Although APOE ε4 carriers are at high risk for cognitive decline, our findings suggest possible intervention targets, including the enhancement of cognitive reserve and improvement of other psychosocial and health factors, to promote cognitive resilience among black and white APOE ε4 carriers.

Using data from the Health, Aging, and Body Composition study, we examined whether low 25-hydroxyvitamin D (25[OH]D) concentrations were associated with prevalent or incident cognitive impairment. Serum 25(OH)D concentrations were measured in 2,786 older adults and categorized as <20 ng/mL, 20 to <30 ng/mL, or ≥30 ng/mL. Cognitive impairment was defined as a score >1.5 standard deviations below race and education specific means on either digit symbol substitution test or modified mini-mental state test. Logistic regression determined the odds of cognitive impairment at baseline and year 5 by 25(OH)D category. 25(OH)D concentrations were <30 ng/mL in 57.3% of whites and 84.6% of blacks. After excluding participants with baseline cognitive impairment (n = 340), 13% of whites and 13% of blacks developed cognitive impairment by year 5. In whites, 25(OH)D concentrations <30 ng/mL were not associated with prevalent or incident cognitive impairment. Black participants with 25(OH)D concentrations <20 ng/mL had a higher odds of prevalent, but not incident cognitive impairment (OR (95% CI): 2.05 (1.08-3.91), p = 0.03) compared to participants with 25(OH)D concentrations ≥30 ng/mL. Low 25(OH)D concentrations were associated with twofold higher odds of prevalent cognitive impairment in blacks.

Background

To investigate the association between diuretics, angiotensin-converting enzyme inhibitors (ACE-I), angiotensin II receptor blockers (AT2RB), and cognitive function.

Methods

This post hoc analysis of the randomized controlled Ginkgo Evaluation of Memory Study trial focuses on 3069 nondemented community-dwelling participants aged >75 years. At baseline visit, detailed information about medication use was collected and five cognitive domains were assessed. Multivariate linear regression analyses were used to assess cross-sectional associations between medication use and cognitive function.

Results

In all, 36% of participants reported history of hypertension and 53% reported antihypertensive medication use, with 17% reporting diuretic, 11% ACE-I, and 2% AT2RB use. Potassium-sparing diuretic use (N = 192) was associated with better verbal learning and memory measured by California Verbal Learning Test as compared with no antihypertensive medication users (β = 0.068, P = .01; β = 0.094, P < .001) and other antihypertensive medication users (β = 0.080, P = .03; β = 0.153, P < .001). Use of ACE-I or AT2RB was not associated with better cognitive function.

Conclusion

Results warrant further investigation into possible protective effects of potassium-sparing diuretics and the role of potassium in mitigating cognitive decline.

Objectives

To examine the relationship between 25-hydroxyvitamin D (25(OH)D) levels and cognitive performance over time in older adults in the Health, Aging and Body Composition (Health ABC) Study.

Design

Prospective cohort study.

Setting

Community-dwelling participants in Pittsburgh, Pennsylvania, and Memphis, Tennessee.

Participants

Well-functioning adults aged 70 to 79 at baseline with serum 25(OH)D measured at the 12-month follow-up visit and cognitive function measured at baseline and 4-year follow-up visit (N = 2,777).

Measurements

Vitamin D status was categorized as 25(OH)D levels of less than 20.0 ng/mL, 20.0 to 29.9 ng/mL, or 30.0 ng/mL or greater. Cognition was measured using the modified Mini-Mental State Examination (3MS) and Digit Symbol Substitution Test (DSST). Linear regression models adjusting for multiple covariates, including age, education, sex, race, site, season, physical activity, and comorbidities, were used in the analysis.

Results

Sixty-eight percent of participants had 25(OH)D levels of less than 30.0 ng/mL. Lower 25(OH)D levels were associated with lower baseline cognitive scores on the 3MS (adjusted mean 89.9, 95% confidence interval (CI) = 89.4-90.4 for <20.0 ng/mL; adjusted mean 90.8, 95% CI = 90.4-91.3 for 20.0-29.9 ng/mL; adjusted mean 90.6, 95% CI = 90.2-91.1 for ≥ 30.0 ng/mL; P trend = .02) and the DSST (adjusted mean 35.2, 95% CI = 34.5-36.0 for <20.0 ng/mL; adjusted mean 35.9, 95% CI = 35.2-36.6 for 20.0-29.9 ng/mL; adjusted mean 37.0, 95% CI = 36.3-37.8 for ≥ 30.0 ng/mL; P trend = .01). Participants with low 25(OH)D levels had greater declines in 3MS scores over 4 years than those with higher levels (least square mean change -1.0, 95% CI = -1.5 to -0.6 for <20.0 ng/mL; least square mean change -0.8, 95% CI = -1.2 to -0.3 for 20.0-29.9 ng/mL; least square mean change -0.2, 95% CI = -0.7 to 0.2 for ≥30.0 ng/mL; P = .05). There was no significant difference in DSST decline according to 25(OH)D level.

Conclusion

Low 25(OH)D levels were associated with worse global cognitive function and greater decline over time according to the 3MS. Intervention trials are needed to determine whether vitamin D supplementation can reduce cognitive decline.

Objectives

The aim of this study was to determine whether use of diuretics, angiotensin-1 receptor blockers (ARB), angiotensin-converting enzyme inhibitors (ACE-I), calcium channel blockers (CCB), or β-blockers (BB) was associated with a reduced risk of Alzheimer disease (AD) dementia in participants with normal cognition or mild cognitive impairment (MCI).

Methods

Secondary longitudinal data analysis of the Ginkgo Evaluation of Memory Study in older adults at least 75 years of age with normal cognition (n = 1,928) or MCI (n = 320) over a median 6.1-year period using Cox proportional hazard models after adjusting for confounders.

Results

Diuretic use was reported by 15.6%, ARB 6.1%, ACE-I 15.1%, CCB 14.8%, and BB 20.5%. Of the 2,248 participants, 290 (13%) developed AD dementia. Hazard ratio for incident AD dementia among participants with normal cognition was 0.51 in diuretic (95% confidence interval [CI] 0.31-0.82), 0.31 in ARB (95% CI 0.14-0.68), 0.50 in ACE-I (95% CI 0.29-0.83), 0.62 in CCB (95% CI 0.35-1.09), and 0.58 in BB (95% CI 0.36-0.93) users and was not significantly altered when mean systolic blood pressure was above 140 mm Hg. In participants with MCI, only diuretic use was associated with decreased risk (hazard ratio = 0.38, 95% CI 0.20-0.73).

Conclusions

Diuretic, ARB, and ACE-I use was, in addition to and/or independently of mean systolic blood pressure, associated with reduced risk of AD dementia in participants with normal cognition, while only diuretic use was associated with reduced risk in participants with MCI.

BACKGROUND:Data are sparse regarding the value of physical activity (PA) surveillance among older adults-particularly among those with mobility limitations. The objective of this study was to examine longitudinal associations between objectively measured daily PA and the incidence of cardiovascular events among older adults in the LIFE (Lifestyle Interventions and Independence for Elders) study. METHODS AND RESULTS:Cardiovascular events were adjudicated based on medical records review, and cardiovascular risk factors were controlled for in the analysis. Home-based activity data were collected by hip-worn accelerometers at baseline and at 6, 12, and 24 months postrandomization to either a physical activity or health education intervention. LIFE study participants (n=1590; age 78.9±5.2 [SD] years; 67.2% women) at baseline had an 11% lower incidence of experiencing a subsequent cardiovascular event per 500 steps taken per day based on activity data (hazard ratio, 0.89; 95% confidence interval, 0.84-0.96; P=0.001). At baseline, every 30 minutes spent performing activities ≥500 counts per minute (hazard ratio, 0.75; confidence interval, 0.65-0.89 [P=0.001]) were also associated with a lower incidence of cardiovascular events. Throughout follow-up (6, 12, and 24 months), both the number of steps per day (per 500 steps; hazard ratio, 0.90, confidence interval, 0.85-0.96 [P=0.001]) and duration of activity ≥500 counts per minute (per 30 minutes; hazard ratio, 0.76; confidence interval, 0.63-0.90 [P=0.002]) were significantly associated with lower cardiovascular event rates. CONCLUSIONS:Objective measurements of physical activity via accelerometry were associated with cardiovascular events among older adults with limited mobility (summary score >10 on the Short Physical Performance Battery) both using baseline and longitudinal data. CLINICAL TRIAL REGISTRATION:URL: http://www.clinicaltrials.gov. Unique identifier: NCT01072500.

Objective

To investigate the association between periventricular white mater hyperintensities (PVWMH) and biomarkers of elevated cerebral β-amyloid (Aβ) in the Alzheimer's Disease Neuroimaging Initiative, a large prospective multicenter observational study.

Methods

The burden of frontal, parietal, and occipital PVWMH on 3T fluid-attenuated inversion recovery MRI was evaluated in 698 cognitively normal participants and participants with mild cognitive impairment (MCI) using a novel semiquantitative visual rating scale. Results were correlated with CSF-Aβ, florbetapir-PET, and fluorodeoxyglucose (FDG)-PET.

Results

Increased burden of parietal, occipital, and frontal PVWMH was associated with elevated cerebral amyloid evidenced by high florbetapir-PET signal (p < 0.01) and low CSF-Aβ (p < 0.01). In logistic regression models, including PVWMH, age, sex, APOE status, vascular risk factors, pulse pressure, vascular secondary prevention medications, education, ethnicity, and race, parietal, occipital, and frontal PVWMH burden was independently associated with high florbetapir-PET uptake (p < 0.05). In a similar logistic regression model, parietal and occipital (p < 0.05) but not frontal (p = 0.05) PVWMH were independently associated with CSF-Aβ. Weaker associations were found between parieto-occipital PVWMH and elevated CSF-tau (p < 0.05) and occipital PVWMH and elevated CSF-phospho-tau (p < 0.05). PVWMH were associated with cerebral hypometabolism on FDG-PET independent of CSF-Aβ levels (p < 0.05). Absolute and consistency of agreement intraclass correlation coefficients were, respectively, 0.83 and 0.83 for frontal, 0.78 and 0.8 for parietal, and 0.45 and 0.75 for occipital PVWMH measurements.

Conclusions

Increased PVWMH were associated with elevated cerebral amyloid independent of potential confounders such as age, APOE genotype, and vascular risk factors. The mechanisms underlying the association between PVWMH and cerebral amyloid remain to be clarified.

Objectives

The aim of this study was to investigate predictors of progressive cognitive deterioration in patients with suspected non-Alzheimer disease pathology (SNAP) and mild cognitive impairment (MCI).

Methods

We measured markers of amyloid pathology (CSF β-amyloid 42) and neurodegeneration (hippocampal volume on MRI and cortical metabolism on [(18)F]-fluorodeoxyglucose-PET) in 201 patients with MCI clinically followed for up to 6 years to detect progressive cognitive deterioration. We categorized patients with MCI as A+/A- and N+/N- based on presence/absence of amyloid pathology and neurodegeneration. SNAPs were A-N+ cases.

Results

The proportion of progressors was 11% (8/41), 34% (14/41), 56% (19/34), and 71% (60/85) in A-N-, A+N-, SNAP, and A+N+, respectively; the proportion of APOE ε4 carriers was 29%, 70%, 31%, and 71%, respectively, with the SNAP group featuring a significantly different proportion than both A+N- and A+N+ groups (p ≤ 0.005). Hypometabolism in SNAP patients was comparable to A+N+ patients (p = 0.154), while hippocampal atrophy was more severe in SNAP patients (p = 0.002). Compared with A-N-, SNAP and A+N+ patients had significant risk of progressive cognitive deterioration (hazard ratio = 2.7 and 3.8, p = 0.016 and p < 0.001), while A+N- patients did not (hazard ratio = 1.13, p = 0.771). In A+N- and A+N+ groups, none of the biomarkers predicted time to progression. In the SNAP group, lower time to progression was correlated with greater hypometabolism (r = 0.42, p = 0.073).

Conclusions

Our findings support the notion that patients with SNAP MCI feature a specific risk progression profile.