20-year depressive symptoms, dementia, and structural neuropathology in older women.

INTRODUCTION: The course of depressive symptoms and dementia risk is unclear, as are potential structural neuropathological common causes. METHODS: Utilizing joint latent class mixture models, we identified longitudinal trajectories of annually assessed depressive symptoms and dementia risk over 21 years in 957 older women (baseline age 72.7 years old) from the Women's Health Initiative Memory Study. In a subsample of 569 women who underwent structural magnetic resonance imaging, we examined whether estimates of cerebrovascular disease and Alzheimer's disease (AD)-related neurodegeneration were associated with identified trajectories. RESULTS: Five trajectories of depressive symptoms and dementia risk were identified. Compared to women with minimal symptoms, women who reported mild and stable and emerging depressive symptoms were at the highest risk of developing dementia and had more cerebrovascular disease and AD-related neurodegeneration. DISCUSSION: There are heterogeneous profiles of depressive symptoms and dementia risk. Common neuropathological factors may contribute to both depression and dementia. Highlights The progression of depressive symptoms and concurrent dementia risk is heterogeneous. Emerging depressive symptoms may be a prodromal symptom of dementia. Cerebrovascular disease and AD are potentially shared neuropathological factors.

The relationship between optimism, MCI, and dementia among postmenopausal women.

OBJECTIVES: The relationship between optimism and cognitive functioning is not fully understood. We examined the association of optimism with risk of mild cognitive impairment (MCI) and dementia in the Women's Health Initiative Memory Study (WHIMS). METHODS: Optimism was measured by the Life Orientation Test-Revised (LOT-R) total score, and optimism and pessimism subscales. A panel of experts adjudicated cognitive endpoints based on annual cognitive assessments. We used cox proportional hazard regression models to examine the association of LOT-R total score and optimism and pessimism sub-scores with MCI/dementia. We also examined the relationship between vascular disease, LOT-R total score, optimism and pessimism, and cognition. RESULTS: Mean age was 70.5 (SD = 3.9) years. The sample (N = 7249) was 87% white, and 29.8% of participants had < 12 years of education. Total LOT-R score (HR = 0.96, 95% CI: 0.94, 0.98, p < 0.001) was associated with lower risk of combined MCI or dementia. More pessimism (HR = 1.08, 95% CI: 1.05, 1.11, p < 0.0001) was associated with higher risk of MCI or dementia after adjustment for ethnicity, education, vascular disease, and depression. No significant relationships emerged from the optimism subscale. CONCLUSION: These data suggest that less pessimism, but not more optimism, was associated with a lower risk of MCI and dementia.

Impact of multivitamin-mineral and cocoa extract on incidence of mild cognitive impairment and dementia: Results from the COcoa Supplement and Multivitamin Outcomes Study for the Mind (COSMOS-Mind).

INTRODUCTION: We assessed the effects of multivitamin-mineral and cocoa extract supplementation on incident mild cognitive impairment (MCI) and all-cause probable dementia. METHODS: COSMOS-Mind (N = 2262), a 2 × 2 factorial, randomized-controlled clinical trial administered a telephone-based cognitive battery at baseline and annually for 3 years. Incidence rates of MCI, and separately dementia, were compared among treatment arms with proportional hazards regression. RESULTS: Over 3 years, 110 incident MCI and 14 incident dementia cases were adjudicated. Incidence rates did not vary by assignment to multivitamin-mineral or cocoa extract (all p's ≥ 0.05); however, statistical power was low. When participants assigned to multivitamin-mineral versus placebo converted to MCI, their scores for global cognition (p = 0.03) and executive function (p < 0.001) were higher and had declined less relative to the previous year (p = 0.03 for global cognition; p = 0.004 for executive function). DISCUSSION: Multivitamin-mineral therapy may provide cognitive resilience, countering conversion to MCI, but not significantly reduce its incidence over 3 years. HIGHLIGHTS: Multivitamin-mineral supplementation did not reduce risks for cognitive impairment. Cocoa extract supplementation did not reduce risks for cognitive impairment. Multivitamin-mineral supplementation slowed cognitive declines for incident mild cognitive impairment.

Self-reported experiences of discrimination and incident dementia.

INTRODUCTION: Discrimination negatively impacts health and may contribute to racial/ethnic disparities in dementia risk. METHODS: Experiences of lifetime and everyday discrimination were assessed among 6509 Multi-Ethnic Study of Atherosclerosis (MESA) participants. We assessed the association of discrimination with incidence of dementia including adjustment for important risk factors, cohort attrition, and we assessed for effect modification by race/ethnicity. RESULTS: Prevalence of any lifetime discrimination in MESA was 42%, highest among Black adults (72%). Over a median 15.7 years of follow-up, there were 466 incident cases of dementia. Lifetime discrimination, but not everyday discrimination, was associated with incident dementia (Wald p = 0.03). Individuals reporting lifetime discrimination in ≥2 domains (compared to none) had greater risk for dementia (hazard ratio: 1.40; 95%: 1.08, 1.82) after adjustment for sociodemographic, clinical, and behavioral risk factors. Associations did not differ by race/ethnicity. CONCLUSIONS: These findings demonstrate an association of greater experiences of lifetime discrimination with incident dementia.

Associations among vascular risk factors, neuroimaging biomarkers, and cognition: Preliminary analyses from the Multi-Ethnic Study of Atherosclerosis (MESA).

INTRODUCTION: Little is known about how antecedent vascular risk factor (VRF) profiles impact late-life brain health. METHODS: We examined baseline VRFs, and cognitive testing and neuroimaging measures (ß-amyloid [Aß] PET, MRI) in a diverse longitudinal cohort (N = 159; 50% African-American, 50% White) from Wake Forest's Multi-Ethnic Study of Atherosclerosis Core. RESULTS: African-Americans exhibited greater baseline Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham stroke risk profile (FSRP), and atherosclerotic cardiovascular disease risk estimate (ASCVD) scores than Whites. We observed no significant racial differences in Aß positivity, cortical thickness, or white matter hyperintensity (WMH) volume. Higher baseline VRF scores were associated with lower cortical thickness and greater WMH volume, and FSRP and CAIDE were associated with Aß. Aß was cross-sectionally associated with cognition, and all imaging biomarkers were associated with greater 6-year cognitive decline. DISCUSSION: Results suggest the convergence of multiple vascular and Alzheimer's processes underlying neurodegeneration and cognitive decline.

Particulate matter and episodic memory decline mediated by early neuroanatomic biomarkers of Alzheimer's disease.

Evidence suggests exposure to particulate matter with aerodynamic diameter <2.5 µm (PM2.5) may increase the risk for Alzheimer's disease and related dementias. Whether PM2.5 alters brain structure and accelerates the preclinical neuropsychological processes remains unknown. Early decline of episodic memory is detectable in preclinical Alzheimer's disease. Therefore, we conducted a longitudinal study to examine whether PM2.5 affects the episodic memory decline, and also explored the potential mediating role of increased neuroanatomic risk of Alzheimer's disease associated with exposure. Participants included older females (n = 998; aged 73-87) enrolled in both the Women's Health Initiative Study of Cognitive Aging and the Women's Health Initiative Memory Study of Magnetic Resonance Imaging, with annual (1999-2010) episodic memory assessment by the California Verbal Learning Test, including measures of immediate free recall/new learning (List A Trials 1-3; List B) and delayed free recall (short- and long-delay), and up to two brain scans (MRI-1: 2005-06; MRI-2: 2009-10). Subjects were assigned Alzheimer's disease pattern similarity scores (a brain-MRI measured neuroanatomical risk for Alzheimer's disease), developed by supervised machine learning and validated with data from the Alzheimer's Disease Neuroimaging Initiative. Based on residential histories and environmental data on air monitoring and simulated atmospheric chemistry, we used a spatiotemporal model to estimate 3-year average PM2.5 exposure preceding MRI-1. In multilevel structural equation models, PM2.5 was associated with greater declines in immediate recall and new learning, but no association was found with decline in delayed-recall or composite scores. For each interquartile increment (2.81 µg/m3) of PM2.5, the annual decline rate was significantly accelerated by 19.3% [95% confidence interval (CI) = 1.9% to 36.2%] for Trials 1-3 and 14.8% (4.4% to 24.9%) for List B performance, adjusting for multiple potential confounders. Long-term PM2.5 exposure was associated with increased Alzheimer's disease pattern similarity scores, which accounted for 22.6% (95% CI: 1% to 68.9%) and 10.7% (95% CI: 1.0% to 30.3%) of the total adverse PM2.5 effects on Trials 1-3 and List B, respectively. The observed associations remained after excluding incident cases of dementia and stroke during the follow-up, or further adjusting for small-vessel ischaemic disease volumes. Our findings illustrate the continuum of PM2.5 neurotoxicity that contributes to early decline of immediate free recall/new learning at the preclinical stage, which is mediated by progressive atrophy of grey matter indicative of increased Alzheimer's disease risk, independent of cerebrovascular damage.

Expanded Demographic Norms for Version 3 of the Alzheimer Disease Centers' Neuropsychological Test Battery in the Uniform Data Set.

BACKGROUND: Norms for the Uniform Data Set Version 3 Neuropsychological Battery are available for cognitively normal individuals based on age, education, and sex; however, these norms do not include race. We provide expanded norms for African Americans and whites. METHODS: Data from 32 Alzheimer's Disease Centers (ADCs) and ADC affiliated cohorts with global Clinical Dementia Rating Scale (CDR) Dementia Staging Instrument scores of 0 were included. Descriptive statistics for each test were calculated by age, sex, race, and education. Multiple linear regressions were conducted to estimate the effect of each demographic variable; squared semipartial correlation coefficients measured the relative importance of variables. RESULTS: There were 8313 participants (16% African American) with complete demographic information, ranging from 6600 to 7885 depending on the test. Lower scores were found for older and less educated groups, and African Americans versus whites. Education was the strongest predictor for most tests, followed in order by age, race, and sex. Quadratic terms were significant for age and education, indicating some nonlinearity, but did not substantially increase R. CONCLUSIONS: Although race-based norms represent incomplete proxies for other sociocultural variables, the appropriate application of these norms is important given the potential to improve diagnostic accuracy and to reduce misclassification bias in cognitive disorders of aging such as Alzheimer disease.

Cognitive resilience among APOE ε4 carriers in the oldest old.

OBJECTIVES: Relatively few APOE ε4+ carriers survive to old age (age 80+) without cognitive impairment (CI); thus, little is known about distinguishing characteristics of resilient APOE ε4+ carriers. Herein, we describe the sociodemographic characteristics of a large sample of resilient APOE ε4+ women from the Women's Health Initiative Memory Study (WHIMS) and compare them to noncarriers and APOE ε4+ women who developed CI before age 80. METHODS: Women were recruited for clinical trials evaluating postmenopausal hormone therapy and incidence of dementia. During posttrial follow-up, cognitive status was adjudicated annually. Among 5716 women, we compared groups by APOE ε4 status using logistic regression, covarying for treatment, demographics, lifestyle, cardiovascular and physical function, well-being, and self-rated general health. RESULTS: Among 557 APOE ε4+ women, those who survived to age 80+ without CI had higher baseline self-rated general health (odds ratio [OR]: 1.02; 95% confidence interval [CI], 1.01-1.04) and cognitive scores (OR: 1.18; 95% CI, 1.12-1.25) than those who did not reach age 80 without CI. Baseline high total cholesterol and low-density lipoprotein (LDL) levels were similar across APOE ε4+ groups but were higher compared with APOE ε4- women. Among women who survived to 80+ without CI, more APOE ε4+ women had a history of high total cholesterol (P = .003) and LDL cholesterol (OR: 1.01; 95% CI, 1.00-1.01). There were no differences in hypertension, diabetes, or other vascular risk factors in APOE ε4+ women compared with noncarriers. CONCLUSIONS: Results highlight the importance of baseline cognitive function and general health for late-life cognition among ε4+ women.

Effect of Intensive vs Standard Blood Pressure Control on Probable Dementia: A Randomized Clinical Trial.

Importance: There are currently no proven treatments to reduce the risk of mild cognitive impairment and dementia. Objective: To evaluate the effect of intensive blood pressure control on risk of dementia. Design, Setting, and Participants: Randomized clinical trial conducted at 102 sites in the United States and Puerto Rico among adults aged 50 years or older with hypertension but without diabetes or history of stroke. Randomization began on November 8, 2010. The trial was stopped early for benefit on its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. The final date for follow-up of cognitive outcomes was July 22, 2018. Interventions: Participants were randomized to a systolic blood pressure goal of either less than 120 mm Hg (intensive treatment group; n = 4678) or less than 140 mm Hg (standard treatment group; n = 4683). Main Outcomes and Measures: The primary cognitive outcome was occurrence of adjudicated probable dementia. Secondary cognitive outcomes included adjudicated mild cognitive impairment and a composite outcome of mild cognitive impairment or probable dementia. Results: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 8563 (91.5%) completed at least 1 follow-up cognitive assessment. The median intervention period was 3.34 years. During a total median follow-up of 5.11 years, adjudicated probable dementia occurred in 149 participants in the intensive treatment group vs 176 in the standard treatment group (7.2 vs 8.6 cases per 1000 person-years; hazard ratio [HR], 0.83; 95% CI, 0.67-1.04). Intensive BP control significantly reduced the risk of mild cognitive impairment (14.6 vs 18.3 cases per 1000 person-years; HR, 0.81; 95% CI, 0.69-0.95) and the combined rate of mild cognitive impairment or probable dementia (20.2 vs 24.1 cases per 1000 person-years; HR, 0.85; 95% CI, 0.74-0.97). Conclusions and Relevance: Among ambulatory adults with hypertension, treating to a systolic blood pressure goal of less than 120 mm Hg compared with a goal of less than 140 mm Hg did not result in a significant reduction in the risk of probable dementia. Because of early study termination and fewer than expected cases of dementia, the study may have been underpowered for this end point. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Association of Intensive vs Standard Blood Pressure Control With Cerebral White Matter Lesions.

Importance: The effect of intensive blood pressure lowering on brain health remains uncertain. Objective: To evaluate the association of intensive blood pressure treatment with cerebral white matter lesion and brain volumes. Design, Setting, and Participants: A substudy of a multicenter randomized clinical trial of hypertensive adults 50 years or older without a history of diabetes or stroke at 27 sites in the United States. Randomization began on November 8, 2010. The overall trial was stopped early because of benefit for its primary outcome (a composite of cardiovascular events) and all-cause mortality on August 20, 2015. Brain magnetic resonance imaging (MRI) was performed on a subset of participants at baseline (n = 670) and at 4 years of follow-up (n = 449); final follow-up date was July 1, 2016. Interventions: Participants were randomized to a systolic blood pressure (SBP) goal of either less than 120 mm Hg (intensive treatment, n = 355) or less than 140 mm Hg (standard treatment, n = 315). Main Outcomes and Measures: The primary outcome was change in total white matter lesion volume from baseline. Change in total brain volume was a secondary outcome. Results: Among 670 recruited patients who had baseline MRI (mean age, 67.3 [SD, 8.2] years; 40.4% women), 449 (67.0%) completed the follow-up MRI at a median of 3.97 years after randomization, after a median intervention period of 3.40 years. In the intensive treatment group, based on a robust linear mixed model, mean white matter lesion volume increased from 4.57 to 5.49 cm3 (difference, 0.92 cm3 [95% CI, 0.69 to 1.14]) vs an increase from 4.40 to 5.85 cm3 (difference, 1.45 cm3 [95% CI, 1.21 to 1.70]) in the standard treatment group (between-group difference in change, -0.54 cm3 [95% CI, -0.87 to -0.20]). Mean total brain volume decreased from 1134.5 to 1104.0 cm3 (difference, -30.6 cm3 [95% CI, -32.3 to -28.8]) in the intensive treatment group vs a decrease from 1134.0 to 1107.1 cm3 (difference, -26.9 cm3 [95% CI, 24.8 to 28.8]) in the standard treatment group (between-group difference in change, -3.7 cm3 [95% CI, -6.3 to -1.1]). Conclusions and Relevance: Among hypertensive adults, targeting an SBP of less than 120 mm Hg, compared with less than 140 mm Hg, was significantly associated with a smaller increase in cerebral white matter lesion volume and a greater decrease in total brain volume, although the differences were small. Trial Registration: ClinicalTrials.gov Identifier: NCT01206062.

Cognitive functioning throughout the treatment history of clinical late-life depression.

OBJECTIVE: Previous investigations into the relationship between late-life depressive symptoms and cognitive functioning have resulted in mixed findings concerning whether or not depressive symptoms and cognitive functioning are related. The mixed reports may be due in part to differences in clinical and nonclinical samples and to inadequate consideration of the dynamic nature (i.e., fluctuating course) of depressive symptoms and cognitive functioning in older adults. The current study examined the chronic, acute, and longitudinal relationships between depressive symptoms and cognitive functioning in older adults in an ongoing treatment study of major depressive disorder (MDD). METHODS: The neurocognitive outcomes of depression in the elderly study operates in a naturalistic treatment milieu using a pharmacological treatment algorithm and regular psychiatric assessment. Four hundred and fifty-three older adults [mean age 70 years, standard deviation (SD) = 7.2] meeting criteria for MDD at study enrollment received annual neuropsychological testing and depressive symptom monitoring for an average of 8.5 years (SD = 4.5). RESULTS: Hierarchical linear modeling revealed that higher age, lower education, and higher average/chronic levels of depressive symptoms were related to lower cognitive functioning. Additionally, results revealed that when an individual's depressive symptoms are higher than is typical for a specific individual, general cognitive function was worse than average. There was no evidence of lagged/longitudinal relationships between depressive symptoms and cognitive functioning in older adults in treatment for MDD. CONCLUSIONS: Cognitive functioning and depressive symptoms are concurrently associated in older adults with MDD, highlighting the potential importance for stabilizing mood symptoms as a means to manage cognitive deficits in late-life depression.

Feasibility of Remote Administration of the Uniform Data Set-Version 3 for Assessment of Older Adults With Mild Cognitive Impairment and Alzheimer's Disease.

OBJECTIVE: Assess the feasibility and concurrent validity of a modified Uniform Data Set version 3 (UDSv3) for remote administration for individuals with normal cognition (NC), mild cognitive impairment (MCI), and early dementia. METHOD: Participants (N = 93) (age: 72.8 [8.9] years; education: 15.6 [2.5] years; 72% female; 84% White) were enrolled from the Wake Forest ADRC. Portions of the UDSv3 cognitive battery, plus the Rey Auditory Verbal Learning Test, were completed by telephone or video within ~6 months of participant's in-person visit. Adaptations for phone administration (e.g., Oral Trails for Trail Making Test [TMT] and Blind Montreal Cognitive Assessment [MoCA] for MoCA) were made. Participants reported on the pleasantness, difficulty, and preference for each modality. Staff provided validity ratings for assessments. Participants' remote data were adjudicated by cognitive experts blinded to the in person-diagnosis (NC [N = 44], MCI [N = 35], Dementia [N = 11], or other [N = 3]). RESULTS: Remote assessments were rated as pleasant as in-person assessments by 74% of participants and equally difficult by 75%. Staff validity rating (video = 92%; phone = 87.5%) was good. Concordance between remote/in-person scores was generally moderate to good (r = .3 -.8; p < .05) except for TMT-A/OTMT-A (r = .3; p > .05). Agreement between remote/in-person adjudicated cognitive status was good (k = .61-.64). CONCLUSIONS: We found preliminary evidence that older adults, including those with cognitive impairment, can be assessed remotely using a modified UDSv3 research battery. Adjudication of cognitive status that relies on remotely collected data is comparable to classifications using in-person assessments.

Examining a Preclinical Alzheimer's Cognitive Composite for Telehealth Administration for Reliability Between In-Person and Remote Cognitive Testing with Neuroimaging Biomarkers.

Background: The preclinical Alzheimer's cognitive composite (PACC) was developed for in-person administration to capture subtle cognitive decline. At the outset of the COVID-19 pandemic, cognitive testing was increasingly performed remotely by telephone or video administration. It is desirable to have a harmonized composite measurement derived from both in-person and remote assessments for identifying cognitive changes and to examine its relationship with common neuroimaging biomarkers. Objective: We defined a telehealth compatible PACC (tPACC) and examined its relationship with neuroimaging biomarkers related to neurodegeneration, brain function and perfusion, white matter integrity, and amyloid-ß. Methods: We examined 648 participants' neuroimaging and in-person and remote cognitive testing data from the Wake Forest Alzheimer's Disease Research Center's Clinical Core cohort (observational study) to calculate a modified PACC (PACC5-RAVLT) score and tPACC scores (in-person and remote). We performed Spearman/intraclass correlation coefficient (ICC) analyses for reliability of tPACC scores and linear regression models to evaluate associations between tPACC and neuroimaging. Bland-Altman plots for agreement were constructed across cognitively normal and impaired (mild cognitive impairment and dementia) participants. Results: There was a significant positive relationship between tPACCin - person and PACC5-RAVLT (Overall group: r2 = 0.94, N = 648), and tPACCin - person and tPACCremote (validation subgroup: ICC = 0.82, n = 53). Overall, tPACC showed significant associations with brain thickness/volume, gray matter perfusion, white matter free water, and amyloid-ß deposition. Conclusions: There is a good agreement between tPACCand PACC5-RAVLTfor cognitively normal and impaired individuals. The tPACC is associated with common neuroimaging markers of Alzheimer's disease.

Reliable change on the Boston naming test.

Serial assessments are commonplace in neuropsychological practice and used to document cognitive trajectory for many clinical conditions. However, true change scores may be distorted by measurement error, repeated exposure to the assessment instrument, or person variables. The present study provides reliable change indices (RCI) for the Boston Naming Test, derived from a sample of 844 cognitively normal adults aged 56 years and older. All participants were retested between 9 and 24 months after their baseline exam. Results showed that a 4-point decline during a 9-15 month retest period or a 6-point decline during a 16-24 month retest period represents reliable change. These cutoff values were further characterized as a function of a person's age and family history of dementia. These findings may help clinicians and researchers to characterize with greater precision the temporal changes in confrontation naming ability.

Vascular and microstructural markers of cognitive pathology.

Introduction: Arterial stiffness may play a role in the development of dementia through poorly understood effects on brain microstructural integrity and perfusion. Methods: We examined markers of arterial stiffness (carotid-femoral pulse wave velocity [cfPWV]) and elevated systolic blood pressure (SBP) in relation to cognitive function and brain magnetic resonance imaging macrostructure (gray matter [GM] and white matter [WM] volumes), microstructure (diffusion based free water [FW] and fractional anisotropy [FA]), and cerebral blood flow (CBF) in WM and GM in models adjusted for age, race, sex, education, and apolipoprotein E ε4 status. Results: Among 460 participants (70 ± 8 years; 44 dementia, 158 mild cognitive impairment, 258 normal cognition), higher cfPWV and SBP were independently associated with higher FW, higher WM hyperintensity volume, and worse cognition (global and executive function). Higher SBP alone was significantly associated with lower WM and GM CBF. Discussion: Arterial stiffness is associated with impaired WM microstructure and global and executive cognitive function.

Robust demographically-adjusted normative data for the Montreal Cognitive Assessment (MoCA): Results from the systolic blood pressure intervention trial.

To generate robust, demographically-adjusted regression-based norms for the Montreal Cognitive Assessment (MoCA) using a large sample of diverse older US adults.Baseline MoCA scores were examined for participants in the Systolic Blood Pressure Intervention Trial (SPRINT). A robust, cognitively-normal sample was drawn from individuals not subsequently adjudicated with cognitive impairment through 4 years of follow-up. Multivariable Beta-Binomial regression was used to model the association of demographic variables with MoCA performance and to create demographically-stratified normative tables.Participants' (N = 5,338) mean age was 66.9 ± 8.8 years, with 35.7% female, 63.1% White, 27.4% Black, 9.5% Hispanic, and 44.5% with a college or graduate education. A large proportion scored below published MoCA cutoffs: 61.4% scored below 26 and 29.2% scored below 23. A disproportionate number falling below these cutoffs were Black, Hispanic, did not graduate from college, or were ≥75 years of age. Multivariable modeling identified education, race/ethnicity, age, and sex as significant predictors of MoCA scores (p<.001), with the best fitting model explaining 24.4% of the variance. Model-based predictions of median MoCA scores were generally 1 to 2 points lower for Black and Hispanic participants across combinations of age, sex, and education. Demographically-stratified norm-tables based on regression modeling are provided to facilitate clinical use, along with our raw data.By using regression-based strategies that more fully account for demographic variables, we provide robust, demographically-adjusted metrics to improve cognitive screening with the MoCA in diverse older adults.

Association of Vascular Risk Scores and Cognitive Performance in a Diverse Cohort: The Multi-Ethnic Study of Atherosclerosis.

BACKGROUND: Vascular risk scores are associated with incident dementia. Information regarding their association with cognitive performance and decline in racially/ethnically diverse cohorts is lacking. METHOD: In 4 392 Multi-Ethnic Study of Atherosclerosis participants (aged 60.1 ± 9.4 years; 53% women; 41% White, 11% Chinese American, 26% African American, 21% Hispanic), we compared associations of Exam 1 (2000-2002) Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE), Framingham Stroke Risk Profile (FSRP), and atherosclerotic cardiovascular disease pooled cohort equation (ASCVD-PCE) risk scores with Exam 5 (2010-2012) Cognitive Abilities Screening Instrument (CASI), Digit Symbol Coding (DSC), and Digit Span (DS) cognitive test performance using multivariable linear regression, and examined racial/ethnic interactions. In 1 838 participants with repeat CASI data at Exam 6 (2016-2018), we related risk scores to odds of a 1-SD decline in CASI performance using multivariable logistic regression. RESULTS: SD increments in each risk score were associated with worse cognitive performance. CAIDE had stronger associations with CASI performance than the FSRP and ASCVD-PCE, but associations of ASCVD-PCE with the DSC and DS were similar to CAIDE (difference in ß [95% CI] = -0.57 [-1.48, 0.34] and -0.21 [-0.43, 0.01], respectively). Race/ethnicity modified associations. For example, associations between CAIDE and CASI were greater in African Americans and Hispanics than in Whites (difference in ß = 0.69 [0.02, 1.36] and 1.67 [0.95, 2.39], respectively). Risk scores were comparably associated with decline in CASI performance. CONCLUSIONS: Antecedent vascular risk scores are associated with cognitive performance and decline in the 4 most common U.S. racial/ethnic groups, but associations differ among risk scores and by race/ethnicity.

Hypertensive Aspects of Cardiometabolic Disorders Are Associated with Lower Brain Microstructure, Perfusion, and Cognition.

BACKGROUND: Cardiometabolic disorders (hypertension, diabetes) are key modifiable risk factors for Alzheimer's disease and related disorders. They often co-occur; yet, the extent to which they independently affect brain structure and function is unclear. OBJECTIVE: We hypothesized their combined effect is greater in associations with cognitive function and neuroimaging biomarkers of white matter (WM) health and cerebral perfusion in a diverse older adult cohort. METHODS: Participants aged 50-85 years received: clinical evaluation, oral glucose tolerance testing, neuroimaging, cognitive testing, and adjudication. Neuroimaging included: T1 (gray [GM]/WM segmentation, regional volumes/thicknesses); FLAIR (WM hyperintensity volume [WMHv]; arterial spin labeling (cerebral blood flow); diffusion tensor imaging (fractional anisotropy [FA]); and neurite orientation dispersion and density imaging (Free Water). Hypertension (HTN) and impaired glucose tolerance (IGT) were staged and cardiometabolic status was categorized (HTN only, IGT only, IGT+HTN, neither). Multivariable linear regression modeled associations with cognitive and neuroimaging measures (covariates: age, gender, race). RESULTS: MRI was available for 478 participants (35% mild cognitive impairment, 10% dementia) with mean age 70±8 years, 74% with HTN, 61% with IGT, and 15% self-identified as Black/African-American. IGT+HTN was significantly associated with cognitive impairment, higher WM Free Water and WMHv, lower FA, and lower GM perfusion compared to neither factor. HTN alone was associated with poorer cognition and lower GM perfusion. Cardiometabolic factors were not associated with GM macrostructure (volumes, temporal lobe cortical thickness) or cognitive status. CONCLUSION: HTN and its co-occurrence with IGT (HTN+IGT) were associated with lower global cognitive performance and reduced GM perfusion and impaired WM microstructure.

Effect of intensive blood pressure control on subtypes of mild cognitive impairment and risk of progression from SPRINT study.

BACKGROUND: To examine the effect of intensive blood pressure control on the occurrence of subtypes of mild cognitive impairment (MCI) and determine the risk of progression to dementia or death. METHODS: Secondary analysis of a randomized trial of community-dwelling adults (≥50 years) with hypertension. Participants were randomized to a systolic blood pressure (SBP) goal of <120 mm Hg (intensive treatment; n = 4678) or <140 mm Hg (Standard treatment; n = 4683). Outcomes included adjudicated MCI, MCI subtype (amnestic, non-amnestic, multi-domain, single domain), and probable dementia. Multistate survival models were used to examine transitions in cognitive status accounting for the competing risk of death. RESULTS: Among 9361 randomized participants (mean age, 67.9 years; 3332 women [35.6%]), 640 participants met the protocol definition for MCI, with intensive treatment reducing the risk of MCI overall (hazard ratio [HR], 0.81 [95% confidence interval {CI}, 0.69-0.94]), as previously reported. This effect was largely reflected in amnestic subtypes (HR, 0.78 [95% CI, 0.66-0.92]) and multi-domain subtypes (HR, 0.78 [95% CI, 0.65-0.93]). An adjudication of MCI, as compared with normal cognitive function, substantially increased the probability of progressing to probable dementia (5.9% [95% CI: 4.5%-7.7%] vs. 0.6% [95% CI: 0.3%-0.9%]) and to death (10.0% [95% CI: 8.3%-11.9%] vs. 2.3% [95% CI: 2.0%-2.7%]) within 2 years. CONCLUSIONS: Intensive treatment reduced the risk for amnestic and multi-domain subtypes of MCI. An adjudication of MCI was associated with increased risk of progression to dementia and death, highlighting the relevance of MCI as a primary outcome in clinical and research settings.

Investigating Predictors of Preserved Cognitive Function in Older Women Using Machine Learning: Women's Health Initiative Memory Study.

BACKGROUND: Identification of factors that may help to preserve cognitive function in late life could elucidate mechanisms and facilitate interventions to improve the lives of millions of people. However, the large number of potential factors associated with cognitive function poses an analytical challenge. OBJECTIVE: We used data from the longitudinal Women's Health Initiative Memory Study (WHIMS) and machine learning to investigate 50 demographic, biomedical, behavioral, social, and psychological predictors of preserved cognitive function in later life. METHODS: Participants in WHIMS and two consecutive follow up studies who were at least 80 years old and had at least one cognitive assessment following their 80th birthday were classified as cognitively preserved. Preserved cognitive function was defined as having a score ≥39 on the most recent administration of the modified Telephone Interview for Cognitive Status (TICSm) and a mean score across all assessments ≥39. Cognitively impaired participants were those adjudicated by experts to have probable dementia or at least two adjudications of mild cognitive impairment within the 14 years of follow-up and a last TICSm score < 31. Random Forests was used to rank the predictors of preserved cognitive function. RESULTS: Discrimination between groups based on area under the curve was 0.80 (95%-CI-0.76-0.85). Women with preserved cognitive function were younger, better educated, and less forgetful, less depressed, and more optimistic at study enrollment. They also reported better physical function and less sleep disturbance, and had lower systolic blood pressure, hemoglobin, and blood glucose levels. CONCLUSION: The predictors of preserved cognitive function include demographic, psychological, physical, metabolic, and vascular factors suggesting a complex mix of potential contributors.