Incident dementia and faster rates of cognitive decline are associated with worse multisensory function summary scores.

INTRODUCTION: We created a summary score for multiple sensory (multisensory) impairment and evaluated its association with dementia. METHODS: We studied 1794 adults aged 70 to 79 who were dementia-free at enrollment and followed for up to 10 years in the Health, Aging, and Body Composition Study. The multisensory function score (0 to 12 points) was based on sample quartiles of objectively measured vision, hearing, smell, and touch summed overall. Risk of incident dementia and cognitive decline (measured by two cognitive tests) associated with the score were assessed in regression models adjusting for demographics and health conditions. RESULTS: Dementia risk was 2.05 times higher (95% confidence interval [CI] 1.50-2.81) comparing "poor" to "good" multisensory score tertiles and 1.45 times higher comparing the "middle" to "good" tertiles (95% CI 1.09-1.91). Each point worse in the multisensory function score was associated with faster rates of cognitive decline (P < .05). CONCLUSIONS: Worsening multisensory function, even at mild levels, was associated with accelerated cognitive aging.

Conscientiousness Is Associated with Lower Risk of Dementia among Black and White Older Adults.

BACKGROUND: While some personality traits may reduce risk of dementia, this is controversial and has not been studied as much among diverse populations. We examined associations between 2 traits - Conscientiousness and Openness to Experience - and risk of dementia among black and white older adults. METHODS: We studied 875 older adults (ages 71-82, 47% black) without prevalent dementia from the Health, Aging and Body Composition study, who completed the NEO Five-Factor Inventory for Conscientiousness and Openness to Experience. Incident dementia over 8 years (mean = 6.9 years) was determined by hospital records, medications, or ≥1.5 SD race-specific decline on the Modified Mini-Mental State Examination. In adjusted models, we investigated associations between each trait and risk of dementia, including for race interactions. RESULTS: Associations between personality traits and dementia risk did not differ by race (interactions: p > 0.7). Higher Conscientiousness was associated with lower dementia risk (adjusted HR per 1SD = 0.78; 95% CI 0.65-0.94). There was no association for Openness to Experience (adjusted HR per 1SD = 0.88; 95% CI 0.71-1.08). CONCLUSIONS: Higher Conscientiousness is associated with lower dementia risk, even among diverse populations. Higher Conscientiousness may be protective, or lower Conscientiousness may be an early symptom of neurodegenerative disease.

High Occurrence of Psychiatric Disorders and Suicidal Behavior Across Dementia Subtypes.

OBJECTIVE: To compare occurrence of clinically diagnosed psychiatric disorders and suicidal behavior (mental health disorders) across dementia subtypes in the largest healthcare system in the United States. METHODS: We aggregated two national databases (Department of Veterans Affairs [VA] National Patient Care Database, National Suicide Prevention Applications Network [SPAN]) and estimated 2-year prevalence of mental health disorders across five dementia subtypes during fiscal years 2012-2013. Using VA healthcare systems throughout the United States, the sample included 56,296 older patients (≥50 years) with Alzheimer's disease (AD; n = 30,578), vascular dementia (VD; n = 17,924), frontotemporal dementia (FTD; n = 1,181), Lewy body dementia (LBD; n = 3,194), and mixed dementia (MD; n = 3,419). Mental health disorders were determined by International Classification of Diseases, Ninth Revision, Clinical Modification codes and the National SPAN. RESULTS: Roughly 25% of patients had at least one mental health disorder, with 2-year prevalence reaching 30%-45% in FTD, VD, LBD, and MD. Compared with other subtypes, patients with FTD had the highest prevalence of mood (19%), anxiety (20%), and substance use (19%) disorders, as well as suicidal behavior (4%), with nearly 0.5% with a suicidal plan/attempt. Those with VD also showed a high prevalence of these disorders (14%-17%). Although patients with LBD and MD had a slightly lower prevalence of mood and anxiety disorders (12%-15%), they had a much lower prevalence of substance use disorders (9%) and suicidal behavior (2%). Patients with AD had the lowest 2-year prevalence of all mental health disorders (<7%). CONCLUSION: Occurrence of mental health disorders is high and differs across dementia subtypes, highlighting the importance of reducing the burden of mental health disorders in dementia subtypes.

Neuropsychological Profile of Lifetime Traumatic Brain Injury in Older Veterans.

OBJECTIVES: The aim of this study was to characterize the neuropsychological profile of lifetime traumatic brain injury (TBI) in older Veterans. METHODS: Participants were 169 older Veterans [mean age=79.1 years (range, 51-97 years), 89% male, 92% Caucasian], 88 with lifetime TBI and 81 without TBI, living in Veterans' retirement homes in independent residence. TBI history was ascertained with the Ohio State TBI Identification Method structured interview. Cognition was assessed with neuropsychological tests: Raw scores were converted to Z-scores compared to age-corrected normative data and combined into five domain composite Z-scores (attention/working memory, learning/memory, language, processing speed, executive functioning). We investigated the association between TBI and performance in each cognitive domain in linear mixed effects models, with and without adjustment for demographics, medical comorbidities, and psychiatric variables. RESULTS: Compared to those without TBI, older Veterans with TBI had greater deficits in processing speed (estimate=-.52; p=.01; f 2=.08 in fully adjusted model) and executive functioning (estimate=-.41; p=.02; f 2=.06 in fully adjusted model) but performed similarly in the attention/working memory, learning/memory, and language domains (all p>.05). TBI-associated deficits were most prominent among individuals with multiple mild TBIs and those with any moderate-to-severe TBI, but were not clearly present among those with single mild TBI. CONCLUSIONS: The neuropsychological profile of lifetime TBI in older Veterans is characterized by slowed processing speed and executive dysfunction, especially among those with greater injury burden. This pattern may reflect long-standing deficits or a TBI-associated cognitive decline process distinct from Alzheimer's disease. (JINS, 2017, 23, 56-64).

From suffering to caring: a model of differences among older adults in levels of compassion.

OBJECTIVE: Compassion is an important contributor to pro-social behavior and maintenance of interpersonal relationships, yet little is known about what factors influence compassion in late life. The aim of this study was to test theories about how past and current stressors and emotional functioning, resilience, and demographic indicators of life experiences are related to compassion among older adults. METHODS: One thousand and six older adults (50-99 years) completed a comprehensive survey including self-report measures of compassion, resilience, past and present stress, and emotional functioning (i.e., stressful life events, perceived stress, and current and prior depression and anxiety), and demographic information. The sample was randomly split, and exploratory and confirmatory regression analyses were conducted testing hypothesized relationships with compassion. RESULTS: Exploratory stepwise regression analysis (n = 650) indicated that participants who reported higher levels of compassion were more likely to be female, not currently in a married/married-like relationship, reported higher resilience levels, and had experienced more significant life events. Age, income level, past and current mental distress, and interactions between resilience and other predictors were not significantly related to compassion. The associations between greater self-reported compassion and being female, having greater resilience, and having experienced more significant life events were supported by a confirmatory stepwise regression analysis (n = 356). CONCLUSIONS: Older women report more compassion than older men. Resilience and significant life events, independently, also appear to facilitate a desire to help others, while current stress and past and present emotional functioning are less relevant. Specificity of findings to older adults is not yet known.

Brain functional correlates of working memory: reduced load-modulated activation and deactivation in aging without hyperactivation or functional reorganization.

We aimed to identify brain functional correlates of working memory performance in aging, in hopes of facilitating understanding of mechanisms that promote better versus worse working memory in late-life. Among 64 healthy adults, aged 23 to 78, we examined the relationship between age, working memory performance, and brain functional response during task performance. We focused on the association between working memory load-modulated functional response and individual differences in performance and whether these function-performance relationships differed with age. As expected, older age was associated with poorer working memory performance. Older age was also associated with reduced load-modulated activation including in bilateral prefrontal and parietal regions and left caudate as well as reduced deactivation including in the medial prefrontal cortex. Contrary to findings of hyperactivation in aging, we found no evidence of increased activation with older age. Positive associations identified between brain response and performance did not differ with age. Our findings suggest that the neural mechanisms underlying better versus worse working memory performance are age-invariant across adulthood, and argue against a pattern of functional reorganization in aging. Results are discussed within the broader literature, in which significant heterogeneity in findings between studies has been common.

Brains of optimistic older adults respond less to fearful faces.

The authors examined the neural correlates of emotion processing and how they relate to individual differences in optimism among older adults. Brain response during processing of fearful faces was measured by functional magnetic resonance imaging in 16 older adults and was correlated with level of optimism. Greater optimism was associated with reduced activation in the fusiform gyrus and frontal regions, which may reflect decreased salience of negative emotional information or better emotion regulation among optimistic individuals. Relationships persisted after taking into account cortical thickness, amygdala volume, and resting perfusion. Findings have potential implications for the promotion of successful aging.

Compensatory brain activity during encoding among older adults with better recognition memory for face-name pairs: an integrative functional, structural, and perfusion imaging study.

Many neuroimaging studies interpret the commonly reported findings of age-related increases in frontal response and/or increased bilateral activation as suggestive of compensatory neural recruitment. However, it is often unclear whether differences are due to compensation or reflective of other cognitive or physiological processes. This study aimed to determine whether there are compensatory age-related changes in brain systems supporting successful associative encoding while taking into account potentially confounding factors including age-related differences in task performance, atrophy, and resting perfusion. Brain response during encoding of face-name pairs was measured using functional magnetic resonance imaging in 10 older and nine young adults and was correlated with memory performance. During successful encoding, older adults demonstrated increased frontal and decreased occipital activity as well as greater bilateral involvement relative to the young. Findings remained significant after controlling for age-related cortical atrophy and hypoperfusion. Among the older adults, greater response was associated with better memory performance. Cognitive aging may involve recruitment of compensatory mechanisms to improve performance or prevent impairment. Results extend previous findings by suggesting that age-related alterations in activation cannot be attributed to the commonly observed findings of poorer task performance, reduced resting perfusion, or cortical atrophy among older adults.

Genetic and environmental contributions to regional cortical surface area in humans: a magnetic resonance imaging twin study.

Cortical surface area measures appear to be functionally relevant and distinct in etiology, development, and behavioral correlates compared with other size characteristics, such as cortical thickness. Little is known about genetic and environmental influences on individual differences in regional surface area in humans. Using a large sample of adult twins, we determined relative contributions of genes and environment on variations in regional cortical surface area as measured by magnetic resonance imaging before and after adjustment for genetic and environmental influences shared with total cortical surface area. We found high heritability for total surface area and, before adjustment, moderate heritability for regional surface areas. Compared with other lobes, heritability was higher for frontal lobe and lower for medial temporal lobe. After adjustment for total surface area, regionally specific genetic influences were substantially reduced, although still significant in most regions. Unlike other lobes, left frontal heritability remained high after adjustment. Thus, global and regionally specific genetic factors both influence cortical surface areas. These findings are broadly consistent with results from animal studies regarding the evolution and development of cortical patterning and may guide future research into specific environmental and genetic determinants of variation among humans in the surface area of particular regions.

Remote Assessment of Cardiovascular Risk Factors and Cognition in Middle-Aged and Older Adults: Proof-of-Concept Study.

BACKGROUND: Adults with cardiovascular disease risk factors (CVRFs) are also at increased risk of developing cognitive decline and dementia. However, it is often difficult to study the relationships between CVRFs and cognitive function because cognitive assessment typically requires time-consuming in-person neuropsychological evaluations that may not be feasible for real-world situations. OBJECTIVE: We conducted a proof-of-concept study to determine if the association between CVRFs and cognitive function could be detected using web-based, self-administered cognitive tasks and CVRF assessment. METHODS: We recruited 239 participants aged ≥50 years (mean age 62.7 years, SD 8.8; 42.7% [n=102] female, 88.7% [n=212] White) who were enrolled in the Health eHeart Study, a web-based platform focused on cardiac disease. The participants self-reported CVRFs (hypertension, high cholesterol, diabetes, and atrial fibrillation) using web-based health surveys between August 2016 and July 2018. After an average of 3 years of follow-up, we remotely evaluated episodic memory, working memory, and executive function via the web-based Posit Science platform, BrainHQ. Raw data were normalized and averaged into 3 domain scores. We used linear regression models to examine the association between CVRFs and cognitive function. RESULTS: CVRF prevalence was 62.8% (n=150) for high cholesterol, 45.2% (n=108) for hypertension, 10.9% (n=26) for atrial fibrillation, and 7.5% (n=18) for diabetes. In multivariable models, atrial fibrillation was associated with worse working memory (ß=-.51, 95% CI -0.91 to -0.11) and worse episodic memory (ß=-.31, 95% CI -0.59 to -0.04); hypertension was associated with worse episodic memory (ß=-.27, 95% CI -0.44 to -0.11). Diabetes and high cholesterol were not associated with cognitive performance. CONCLUSIONS: Self-administered web-based tools can be used to detect both CVRFs and cognitive health. We observed that atrial fibrillation and hypertension were associated with worse cognitive function even in those in their 60s and 70s. The potential of mobile assessments to detect risk factors for cognitive aging merits further investigation.

A review of the brain structure correlates of successful cognitive aging.

Unimpaired cognition is an important feature of successful aging. Differences in cognitive performance among healthy older adults may be related to differences in brain structure. The authors reviewed the literature to examine the relationship between brain-structure size and cognitive performance in older adults. Eighty-three percent of studies found at least one positive relationship between these factors; however, findings were variable. Positive relationships emerged most consistently between the hippocampal formation and global cognition and memory and between frontal measures and executive function. Additional longitudinal study is needed to further evaluate structure-cognition relationships in older adulthood and across the adult lifespan.

Schizophrenia patients lack normal positive correlation between age and brain response during verbal learning.

OBJECTIVE: To investigate the differences in the relationship of age to brain function among individuals with schizophrenia and a healthy comparison group. The authors hypothesized that the correlation with age would be more strongly negative among schizophrenia patients, particularly in the frontal cortex. DESIGN: Cross-sectional measures of functional MRI (fMRI) brain response were correlated with age in both groups. SETTING: Participants came to university research facilities for testing. PARTICIPANTS: The authors analyzed data from 30 patients with Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition schizophrenia or schizoaffective disorder ranging in age from 25 to 68 years and 14 healthy comparison participants ranging in age from 21 to 70 years. MEASUREMENTS: Brain response during word pair learning was measured with fMRI in each voxel of the brain. This measure was correlated with age within each group and the correlations were compared across groups in regions of interest determined a priori and based on a whole-brain analysis. In exploratory analyses, the authors examined the interaction of task performance with age and study group. RESULTS: The correlations between age and brain response were more positive in the healthy group than in the schizophrenia group in several regions, including right lateral prefrontal cortex and clusters in midline precuneus and right superior temporal gyrus. Interactions with task performance suggest that age effects on brain function relate differently to cognitive output in patients and comparison participants. CONCLUSIONS: There is no strong evidence that functional brain response during learning changes significantly with age among schizophrenia patients, in contrast to findings of positive associations with age among healthy individuals.

Multiple Sensory Impairment Is Associated With Increased Risk of Dementia Among Black and White Older Adults.

BACKGROUND: Few studies have examined impairment in multiple senses (multisensory impairment) and risk of dementia in comparison to having a single or no sensory impairment. METHODS: We studied 1,810 black and white nondemented participants from Health, Aging, and Body Composition (Health ABC) Study aged 70-79 years at enrollment. Sensory impairment was determined at our study baseline (Year 3-5 of Health ABC) using established cut points for vision (Bailey-Lovie visual acuity and Pelli-Robson contrast sensitivity test), hearing (audiometric testing), smell (12-item Cross-Cultural Smell Identification Test), and touch (peripheral nerve function tests). Incident dementia over 10 years of follow-up was based on hospitalization records, dementia medications, or at least 1.5 SD decline in Modified Mini-Mental State Examination score (race-specific). Cox proportional hazard models with adjustment for demographics, health behaviors, and health conditions evaluated the relationship between risk of dementia and increasing number of sensory impairments. RESULTS: Sensory impairments were common: 28% had visual impairment, 35% had hearing loss, 22% had poor smell, 12% had touch insensitivity; 26% had more than two impairments, and 5.6% had more than three sensory impairments. Number of impairments was associated with risk of dementia in a graded fashion (p < .001). Compared to no sensory impairments, the adjusted hazard ratio was 1.49 (95% CI: 1.12, 1.98) for one sensory impairment, 1.91 (95% CI: 1.39, 2.63) for two sensory impairments, and 2.85 (95% CI: 1.88, 4.30) for more than three sensory impairments. CONCLUSIONS: Multisensory impairment was strongly associated with increased risk of dementia. Although, the nature of this relationship needs further investigation, sensory function assessment in multiple domains may help identify patients at high risk of dementia.

Interventions involving a major dietary component improve cognitive function in cognitively healthy adults: a systematic review and meta-analysis.

Accumulating evidence suggests a role for diet in promoting brain health. The purpose of this systematic review was to (1) quantitatively assess whether interventions with a major dietary component can enhance cognition in cognitively healthy adults and (2) identify responsive domains of cognition to inform the design of future dietary trials. Electronic databases were systematically searched to find eligible randomized controlled trials that assessed the effect of interventions with a major dietary component on cognitive function or incident dementia in adults without known cognitive impairment. Standardized mean differences (SMDs) (95% confidence interval [CI]) were combined using a random-effects meta-analysis, and tests of homogeneity of variance were calculated. Two trials reported dementia outcomes and were qualitatively described. Fifteen trials encompassing 6480 participants were eligible for meta-analysis. Compared to control, intervention improved performance on measures of global cognition (SMD = 0.14, 95% CI 0.01-0.27, P = .05, I2 76%), executive function (SMD = 0.11, 95% CI 0.04-0.18, P = .003, I2 0%), and processing speed (SMD = 0.12, 95% CI 0.05-0.19, P = .001, I2 0%). There was no effect of intervention on delayed memory (SMD = 0.04, 95% CI -0.02 to 0.09, P = .18, I2 4%). Significant heterogeneity and funnel plot asymmetry were detected for global cognition, but removal of studies with high risk of bias did not change the pooled findings. Current evidence is limited but indicates that diverse interventions improve nonmemory cognitive functions during normal cognitive aging. Measures of executive function and processing speed should be considered as feasible end points in future dietary intervention trials.

Systematic Multi-Domain Alzheimer's Risk Reduction Trial (SMARRT): Study Protocol.

This article describes the protocol for the Systematic Multi-domain Alzheimer's Risk Reduction Trial (SMARRT), a single-blind randomized pilot trial to test a personalized, pragmatic, multi-domain Alzheimer's disease (AD) risk reduction intervention in a US integrated healthcare delivery system. Study participants will be 200 higher-risk older adults (age 70-89 years with subjective cognitive complaints, low normal performance on cognitive screen, and ≥ two modifiable risk factors targeted by our intervention) who will be recruited from selected primary care clinics of Kaiser Permanente Washington, oversampling people with non-white race or Hispanic ethnicity. Study participants will be randomly assigned to a two-year Alzheimer's risk reduction intervention (SMARRT) or a Health Education (HE) control. Randomization will be stratified by clinic, race/ethnicity (non-Hispanic white versus non-white or Hispanic), and age (70-79, 80-89). Participants randomized to the SMARRT group will work with a behavioral coach and nurse to develop a personalized plan related to their risk factors (poorly controlled hypertension, diabetes with evidence of hyper or hypoglycemia, depressive symptoms, poor sleep quality, contraindicated medications, physical inactivity, low cognitive stimulation, social isolation, poor diet, smoking). Participants in the HE control group will be mailed general health education information about these risk factors for AD. The primary outcome is two-year cognitive change on a cognitive test composite score. Secondary outcomes include: 1) improvement in targeted risk factors, 2) individual cognitive domain composite scores, 3) physical performance, 4) functional ability, 5) quality of life, and 6) incidence of mild cognitive impairment, AD, and dementia. Primary and secondary outcomes will be assessed in both groups at baseline and 6, 12, 18, and 24 months.

Interactive Effect of Traumatic Brain Injury and Psychiatric Symptoms on Cognition among Late Middle-Aged Men: Findings from the Vietnam Era Twin Study of Aging.

Traumatic brain injury (TBI), post-traumatic stress disorder (PTSD), and depressive symptoms each increase the risk for cognitive impairment in older adults. We investigated whether TBI has long-term associations with cognition in late middle-aged men, and examined the role of current PTSD/depressive symptoms. Participants were 953 men (ages 56-66) from the Vietnam Era Twin Study of Aging (VETSA), who were classified by presence or absence of (1) history of TBI and (2) current elevated psychiatric symptoms (defined as PTSD or depressive symptoms above cutoffs). TBIs had occurred an average of 35 years prior to assessment. Participants completed cognitive testing examining nine domains. In mixed-effects models, we tested the effect of TBI on cognition including for interactions between TBI and elevated psychiatric symptoms. Models adjusted for age, pre-morbid cognitive ability assessed at average age 20 years, apolipoprotein E genotype, and substance abuse; 33% (n = 310) of participants had TBI, mostly mild and remote; and 23% (n = 72) of those with TBI and 18% (n = 117) without TBI had current elevated psychiatric symptoms. TBI and psychiatric symptoms had interactive effects on cognition, particularly executive functioning. Group comparison analyses showed that men with both TBI and psychiatric symptoms demonstrated deficits primarily in executive functioning. Cognition was largely unaffected in men with either risk factor in isolation. Among late middle-aged men, the combination of even mild and very remote TBI with current elevated psychiatric symptoms is associated with deficits in executive function and related abilities. Future longitudinal studies should investigate how TBI and psychiatric factors interact to impact brain aging.

Occupational cognitive complexity in earlier adulthood is associated with brain structure and cognitive health in midlife: The CARDIA study.

OBJECTIVE: In line with cognitive reserve theory, higher occupational cognitive complexity is associated with reduced cognitive decline in older adulthood. How and when occupational cognitive complexity first exerts protective effects during the life span remains unclear. We investigated associations between occupational cognitive complexity during early to midadulthood and brain structure and cognition in midlife. METHOD: Participants were 669 adults from the Coronary Artery Risk Development in Young Adults study (aged 18-30 years at baseline, 52% female, 38% Black). We calculated scores reflecting occupational cognitive complexity using Census Occupation Codes (years 10 and 15) and Occupational Information Network (O*NET) data. At year 25, participants had structural brain magnetic resonance imaging, diffusion tensor imaging, and cognitive testing (Rey Auditory Verbal Learning Test, Digit Symbol Substitution Test, Stroop). In adjusted mixed models, we examined associations between occupational cognitive complexity during early to midadulthood and midlife brain structure, specifically gray matter volume and white matter fractional anisotropy, and cognition in midlife (all outcomes converted to z-scores). RESULTS: Higher occupational cognitive complexity was associated with greater white matter fractional anisotropy (estimate = 0.10, p = .01) but not gray matter volume. Higher occupational cognitive complexity was associated with better Digit Symbol Substitution Test (estimate = 0.13, p < .001) and Stroop (estimate = 0.09, p = .01) performance but not Rey Auditory Verbal Learning Test performance. CONCLUSIONS: Occupational cognitive complexity earlier in adulthood is associated with better white matter integrity, processing speed, and executive function in midlife. These associations may capture how occupational cognitive complexity contributes to cognitive reserve. (PsycINFO Database Record (c) 2018 APA, all rights reserved).

Trajectories of Depressive Symptoms in Older Adults and Risk of Dementia.

IMPORTANCE: Depression has been identified as a risk factor for dementia. However, most studies have measured depressive symptoms at only one time point, and older adults may show different patterns of depressive symptoms over time. OBJECTIVE: To investigate the association between trajectories of depressive symptoms and risk of dementia in older adults. DESIGN, SETTING, AND PARTICIPANTS: This was a prospective cohort investigation of black and white community-dwelling older adults in the Health, Aging, and Body Composition study. Participants were enrolled between May 1997 and June 1998 and followed up through 2001-2002. The dates of this analysis were September 2014 to December 2015. The setting was community research centers in Memphis, Tennessee, and Pittsburgh, Pennsylvania. Trajectories of depressive symptoms were assessed from baseline to year 5. Symptoms were measured with the Center for Epidemiologic Studies Depression Scale Short Form, and trajectories were calculated using latent class growth curve analysis. MAIN OUTCOMES AND MEASURES: Incident dementia through year 11, determined by dementia medication use, hospital records, or significant cognitive decline (≥1.5 SD race-specific decline on the Modified Mini-Mental State Examination). We examined the association between depressive symptom trajectories and dementia incidence using Cox proportional hazards regression models adjusted for demographics, health factors that differed between groups, and cognition during the depressive symptom assessment period (baseline to year 5). RESULTS: The analytic cohort included 2488 black and white older adults with repeated depressive symptom assessments from baseline to year 5 who were free of dementia throughout that period. Their mean (SD) age at baseline was 74.0 (2.8) years, and 53.1% (n = 1322) were female. The following 3 depressive symptom trajectories were identified: consistently minimal symptoms (62.0% [n = 1542] of participants), moderate and increasing symptoms (32.2% [n = 801] of participants), and high and increasing symptoms (5.8% [n = 145] of participants). Compared with the consistently minimal trajectory, having a high and increasing depressive symptom trajectory was associated with significantly increased risk of dementia (fully adjusted hazard ratio, 1.94; 95% CI, 1.30-2.90), while the moderate and increasing trajectory was not associated with risk of dementia after full adjustment. Sensitivity analyses indicated that the high and increasing trajectory was associated with dementia incidence, while depressive symptoms at individual time points were not. CONCLUSIONS AND RELEVANCE: Older adults with a longitudinal pattern of high and increasing depressive symptoms are at high risk for dementia. Individuals' trajectory of depressive symptoms may inform dementia risk more accurately than one-time assessment of depressive symptoms.

Memory complaints and risk of cognitive impairment after nearly 2 decades among older women.

OBJECTIVES: To investigate the association between subjective memory complaints (SMCs) and long-term risk of cognitive impairment in aging because most previous studies have followed individuals for only a few years. METHODS: Participants were 1,107 cognitively normal, community-dwelling older women (aged 65 years and older at baseline) in a prospective study of aging. SMCs were assessed shortly after baseline and repeatedly over time with the yes/no question, "Do you feel you have more problems with memory than most?" Cognitive status 18 years later (normal or impaired with mild cognitive impairment or dementia) was determined by an expert panel. Using logistic regression, we investigated the association between SMCs over time and risk of cognitive impairment, adjusting for demographics, baseline cognition, and characteristics that differed between those with and without SMCs. RESULTS: At baseline, 8.0% of participants (n = 89) endorsed SMCs. Baseline SMCs were associated with increased risk of cognitive impairment 18 years later (adjusted odds ratio [OR] = 1.7, 95% confidence interval 1.1-2.8). Results were unchanged after excluding participants with depression. The association between SMCs and cognitive impairment was greatest at the last SMC assessment time point (18 years before diagnosis: adjusted OR = 1.7 [1.1-2.9]; 14 years before diagnosis: adjusted OR = 1.6 [0.9-2.7]; 10 years before diagnosis: adjusted OR = 1.9 [1.1-3.1]; 4 years before diagnosis: adjusted OR = 3.0 [1.8-5.0]). CONCLUSIONS: SMCs are associated with cognitive impairment nearly 2 decades later among older women. SMCs may be a very early symptom of an insidious neurodegenerative disease process, such as Alzheimer disease.

Cognitive resilience to apolipoprotein E ε4: contributing factors in black and white older adults.

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.