Domain-specific Cognitive Decline Research Articles

Longitudinal relationships between Aβ and tau to executive function and memory in cognitively normal older adults

The early accumulation of AD pathology such as Aβ and tau in cognitively normal older people is predictive of cognitive decline, but it has been difficult to dissociate the cognitive effects of these two proteins. Early Aβ and tau target distinct brain regions that have different functional roles. Here, we assessed specific longitudinal pathology-cognition associations in seventy-six cognitively normal older adults from the Berkeley Aging Cohort Study who underwent longitudinal PiB PET, FTP PET, and cognitive assessments. Using linear mixed-effects models to estimate longitudinal changes and residual approach to characterizing cognitive domain-specific associations, we found that Aβ accumulation, especially in frontal/parietal regions, was associated with faster decline in executive function, not memory, whereas tau accumulation, especially in left entorhinal/parahippocampal regions, was associated with faster decline in memory, not executive function, supporting an “Aβ-executive function, tau-memory” double-dissociation in cognitively normal older people. These specific relationships between accumulating pathology and domain-specific cognitive decline may be due to the particular vulnerabilities of the frontal-parietal executive network to Aβ and temporal memory network to tau.

Racial and ethnic differences in the association between depressive symptoms and cognitive outcomes in older adults: Findings from KHANDLE and STAR.

Depressive symptoms are associated with higher risk of dementia, but how they impact cognition in diverse populations is unclear. Asian, Black, Latino, or White participants (n=2227) in the Kaiser Healthy Aging and Diverse Life Experiences (age 65+) and the Study of Healthy Aging in African Americans (age 50+) underwent up to three waves of cognitive assessments over 4 years. Multilevel models stratified by race/ethnicity were used to examine whether depressive symptoms were associated with cognition or cognitive decline and whether associations differed by race/ethnicity. Higher depressive symptoms were associated with lower baseline verbal episodic memory scores (-0.06, 95% CI: -0.12, -0.01; -0.15, 95% CI: -0.25, -0.04), and faster decline annually in semantic memory (-0.04, 95% CI: -0.07, -0.01; -0.10, 95% CI: -0.15, -0.05) for Black and Latino participants. Depressive symptoms were associated with lower baseline but not decline in executive function. Depressive symptoms were associated with worse cognitive outcomes, with some evidence of heterogeneity across racial/ethnic groups. We examined whether baseline depressive symptoms were differentially associated with domain-specific cognition or cognitive decline by race/ethnicity. Depressive symptoms were associated with worse cognitive scores for all racial/ethnic groups across different domains examined. Higher depressive symptoms were associated with faster cognitive decline for semantic memory for Black and Latino participants. The results suggest a particularly harmful association between depressive symptoms and cognition in certain racial/ethnic groups.

Hypertension, Cognitive Decline, and Mild Cognitive Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging Results (SOL-INCA).

Hypertension can have deleterious effects on cognitive function; however, few studies have examined its effects on cognition among Hispanics/Latinos. To assess associations between hypertension status with 1) change in cognitive performance, and 2) having mild cognitive impairment (MCI) among diverse Hispanics/Latinos. This population-based, prospective cohort, multisite study included Hispanic/Latino adults aged 45 to 72 years in enrolled in the Hispanic Community Health Study/Study of Latinos at Visit 1 (2008-2011; mean age of 63.40±8.24 years), and the Study of Latinos-Investigation of Neurocognitive Aging at Visit 2 (2016-2018), with a mean follow-up duration of 7 years (n = 6,173). Hypertension status was assessed at both visits: normotension (no hypertension), incident hypertension (only at Visit 2), and persistent hypertension (at both visits). We examined change in cognitive performance and having MCI (only assessed at Visit 2) relative to hypertension status and adjusted for demographics and cardiovascular disease risk factors. Compared to normotension, persistent hypertension was associated with significantly increased decline in verbal fluency (β= -0.08; CI = [-0.16;-0.01]; p < 0.05), and processing speed (β= -0.11; CI = [-0.20;-0.02]; p < 0.05). Incident hypertension was not associated with significant change in cognitive performance. Both incident (OR = 1.70; CI = [1.16;2.50]; p < 0.01) and persistent hypertension (OR = 2.13; CI = [1.57;2.88]; p < 0.001) were associated with significantly higher odds ratios of having MCI. These findings indicate that persistent hypertension is associated with clinical impairment and domain-specific cognitive decline in middle-aged and older Hispanics/Latinos. It underscores the importance of monitoring blood pressure in routine healthcare visits beginning at midlife in this population to reduce the burden of cognitive decline.

Brain age gap and decline in specific cognitive domains after stroke

Brain age gap and decline in specific cognitive domains after stroke

PTSD IS ASSOCIATED WITH LONGITUDINAL CHANGES IN DOMAIN-SPECIFIC COGNITIVE FUNCTION IN OLDER ADULTS

Abstract Posttraumatic stress disorder (PTSD) is associated with an increased risk for all-type dementia yet whether PTSD is associated with domain-specific cognitive decline, that may lead to dementia, is unknown. Using existing data from the National Alzheimer’s Coordinating Center, we tested the hypothesis that PTSD is associated with cognitive decline in episodic memory, working memory and attention, and executive function. After exclusion for history of dementia, stroke, Down syndrome, Parkinson’s and Alzheimer’s diseases, schizophrenia, and neurodevelopmental disorders, 130 (1.25%) participants with PTSD and 10,261 (98.75%) without PTSD remained. Prior to analysis, inverse probability of treatment weighting was used to adjust for confounding. Inverse probability estimates were based on PTSD status and conditional on covariates for age, sex, race, ethnicity, APOE ɛ4 status, anxiety, depression, TBI status, diabetes, and hypertension. Generalized estimating equations (GEE)-type linear regression models with robust standard errors were fit to the weighted data for z-scores for each cognitive domain. During the study, unexpectedly, PTSD was associated with an additional .043 standard deviations of improvement in episodic memory (b = .043, 95%CI: .020, .066) compared to the same population without PTSD. Expectedly, PTSD was associated with an additional .143 standard deviations of decline in working memory and attention (b = -.143, 95% CI: -.225, -.062) and an additional .415 standard deviations of decline in executive function (b = -.415, 95%CI: -.563, -.267). Investigations are ongoing to probe the unexpected finding for episodic memory. These findings suggest that PTSD should potentially be a target for early prevention of cognitive decline.

POLYMORPHISMS IN INFLAMMATORY CYTOKINES NOT ASSOCIATED WITH COGNITIVE TRAJECTORIES IN OLDER ADULTS

Abstract Inflammation and key polymorphisms in inflammatory cytokine genes have been associated with increased Alzheimer’s disease (AD) risk. It is unclear if the same polymorphisms also predict domain-specific cognitive decline, that could eventually lead to AD/dementia, in otherwise healthy older adults. We investigated whether specific single nucleotide polymorphisms (SNPs) in three cytokine genes, IL-1β (rs16944; A or AA at -511), IL-6 (rs1800795; C or CC at -174), and TNFα (rs1800629; A or AA at -308), were associated with differential longitudinal trajectories of global cognitive function, episodic memory, attention and working memory, and executive function. Participants were 324 non-demented older adults (Mage=72.8 years at first visit, SD=6.09, age range 57-92 years) who completed 9 research visits, on average. Slopes were examined after adjustment for baseline age, sex, education, conversion to MCI or dementia during study, and APOE ɛ4 status. Findings indicated no statistically significant relationships between the SNPs of interest and longitudinal trajectories (spanning up to 16 years) of cognitive functioning in any cognitive domain examined. Other factors related to AD may be necessary for these SNPs to have significant brain-related effects. Attempts were made to further validate the non-significant findings by conducting post-hoc analyses to determine whether these SNPs were associated with plasma biomarker levels in this sample of healthy older adults. However, variability between and within the assays precluded confidence in the results. Further research is needed to determine whether these SNP genotypes are associated with concentrations of their respective blood-plasma biomarkers in non-demented older adults.

CONSEQUENCES OF PERCEIVED STRESS ON COGNITIVE DECLINE AND BLOOD PRESSURE AS A MODERATOR IN OLDER BLACK AMERICANS

Abstract Previous research suggests that perceptions of stress shape cognitive health outcomes. However, few studies have explored this association longitudinally. The aim of this study was to determine whether perceived stress is associated with cognitive changes over time and if blood pressure (BP) acts as a moderator in a sample of older Blacks 48 to 95 years of age, who were enrolled in the Baltimore Study of Black Aging—Patterns of Cognitive Aging and interviewed at two time points, approximately 3 years apart (N = 450). Cognition included 5 domains: working memory, processing speed, verbal memory, vocabulary, and inductive reasoning. Three readings of orthostatic BP were collected and mean systolic (range = 82-230.3 mmHg) and diastolic BP (range = 51-136.7 mmHg) values were calculated for each participant. Results from the linear regression model showed no direct effect of perceived stress on cognitive decline. Systolic (F(3,426)= 4.37, p= 0.0048) and diastolic (F(3,426) = 3.26 p=0.0215) BP modified the relationship between stress and inductive reasoning at follow-up but was not related to any other cognitive domains, adjusting for age, sex, education, depressive symptoms, comorbidities, and baseline cognition. These important findings demonstrate the joint effects of stress and BP on cognition, highlighting the need for more research documenting the underlying processes and risk factors for domain-specific cognitive decline. The potential benefits of this approach provide a basis for developing cognitive interventions for this population of Black Americans.

Optimal cardiovascular health is associated with slower cognitive decline.

Life's Simple 7, a lifestyle and cardiovascular index associated with cognition, has been updated to Life's Essential 8 (LE8) to include sleep. LE8 has been related to cardiovascular outcomes but its association with cognition is unclear. In this longitudinal analysis of the Brazilian Longitudinal Study of Adult Health (ELSA-Brasil), LE8 score was based on health behaviors (diet, physical activity, nicotine exposure, and sleep health) as well as health-related factors (body mass index, blood lipids, blood glucose, and blood pressure). Cognition was assessed in three waves, 4 years apart, using the Consortium to Establish a Registry for Alzheimer's Disease - Word List, semantic and phonemic verbal fluency, the Trail-Making Test B (TMT-B), and a global composite score. We used linear mixed-model analysis, inverse probability weighting, and interaction analysis. At baseline, the mean age of the study cohort was 51.4 ± 8.9 years, 56% were women, and 53% were White. Higher baseline LE8 scores were associated with slower decline in global cognition (β = 0.001, 95% confidence interval [CI] 0.001, 0.002; p < 0.001), memory (β = 0.001, 95% CI 0.000, 0.002; p = 0.013), verbal fluency (β = 0.001, 95% CI 0.000, 0.002; p = 0.003), and TMT-B (β = 0.004, 95% CI 0.003, 0.005; p < 0.001). This association was mainly driven by LE8 health factors, particularly blood glucose and blood pressure. Age, sex, and race were modifiers of the association between LE8 and global cognitive decline (p < 0.001), suggesting it was more pronounced in older, male, and Black participants. Higher baseline LE8 scores were associated with slower global and domain-specific cognitive decline during 8 years of follow-up, mainly due to health factors such as blood glucose and blood pressure. Sociodemographic factors were modifiers of this association.

Low-Grade systemic inflammation is associated with domain-specific cognitive performance and cognitive decline in older adults: Data from the TUDA study

Studies examining the relationships between chronic inflammation, cognitive function and cognitive decline in older adults have yielded conflicting results. In a large cohort of older adults free from established dementia (n = 3270; 73.1 ± 7.9 years; 68.4% female), we evaluated the cross-sectional and longitudinal relationships between serum cytokines (IL-6, IL-10, TNF-α) and both global and domain-specific cognitive performance (Repeatable Battery for Assessment of Neuropsychological Status [RBANS]). Higher IL-6 (OR: 1.33; 1.06, 1.66, p = 0.01), TNF-α (OR: 1.35; 1.09, 1.67, p = 0.01) and IL-6:IL-10 Ratio (OR: 1.43; 1.17, 1.74, p = 0.001) were cross-sectionally associated with impaired global RBANS performance. For specific cognitive domains, greatest effect sizes were observed between higher TNF-α levels and poorer visual-spatial and attention performance. In a subset of participants (n = 725; 69.8 ± 5.5 years; 67.0% female) with repeat assessment performed at a median of 5.4 years, only higher baseline IL-6:IL-10 ratio was associated with impaired incident overall, immediate memory and visual-spatial performance. Associations were stronger in females, but not modified by age or APOE genotype.

Associations of Orthostatic Hypotension and Orthostatic Intolerance with Domain-Specific Cognitive Decline in Patients with Early Parkinson Disease: An 8-Year Follow-up

ObjectiveAlthough orthostatic hypotension (OH) and orthostatic intolerance (OI) are prevalent in patients with Parkinson disease (PD), it remains unclear how these conditions primarily affect the trajectory of decline in specific cognitive domains. This study aimed to explore the effects of OH and OI on longitudinal domain-specific cognitive changes in patients with PD. DesignAn 8-year follow-up of the Parkinson Progression Markers Initiative cohort study. Setting and ParticipantsA total of 403 patients with early, untreated PD and 195 matched healthy controls were included. They were classified into OH, OI, and normal groups. OH was defined according to the international consensus, and OI was defined as the presence of orthostatic symptoms without meeting the criteria for OH. MethodsThe patients underwent detailed neuropsychological testing annually for up to 8 years of follow-up. Linear mixed effects models were used to investigate the associations between OH, OI, and longitudinal cognitive changes. ResultsThe prevalence of both OH and OI in patients with PD was significantly higher than that in controls (13.4% vs 7.2%, P = .002, for OH, and 29.3% vs 14.4%, P < .001, for OI). The OH group in patients with PD showed a faster decline in Letter-Number Sequencing (LNS) (β = −0.11, 95% CI −0.20 to −0.02, t = −2.44, P = .015) and Semantic Fluency Test (SFT) (β = −0.44, 95% CI –0.81 to −0.08, t = −2.42, P = .016) scores than the normal group. Similarly, the OI group showed a steeper decline in LNS (β = −0.08, 95% CI –0.14 to −0.01, t = −2.20, P = .028) and SFT (β = −0.36, 95% CI –0.63 to −0.08, t = −2.55, P = .011) scores compared to the normal group. There were no significant longitudinal changes in the other neuropsychological test scores between the groups. Conclusions and ImplicationsBoth OH and OI may be associated with a faster decline in executive function among cognitive domains of patients with PD. These findings may highlight the potential importance of orthostatic blood pressure control in PD patients with OH and even those with orthostatic symptoms without OH.

Evidence-Based Multivariate Normal Tissue Complication Probability (NTCP) Study of Domain-Specific Cognitive Decline after Partial Brain RT

Beyond the hippocampus, there are no evidence-based dose constraints for eloquent brain structures which subserve memory and attention/processing speed. We performed a multivariate normal tissue complication probability analysis of post-RT neurocognitive decline, examining dosimetric predictors of eloquent brain regions. Data were analyzed from a prospective longitudinal clinical trial. Patients (n = 78) with primary brain tumors receiving fractionated RT complete a comprehensive neurocognitive evaluation and high-resolution volumetric and diffusion MRI at baseline and 6 months post-RT. Image processing using robust, validated automated segmentation parcellated individual WM tracts, cortical regions, and hippocampi. Well-validated neurocognitive tests including Delis-Kaplan Executive Function System and Wechsler Adult Intelligence Scale-IV coding (attention/processing), Boston Naming Test (language) and Hopkins Verbal Learning Test and Brief Visuospatial Memory Test (verbal/visuospatial memory) were assessed. Reliable change indices adjusted for practice effects (RCI-PE) were calculated for each patient between baseline and 6 months; a negative RCI-PE was scored as decline. Univariate logistic regression was performed with mean and max dose to structures of interest as well as clinical variables. Multivariate model building was performed using automated bootstrapped logistic regression, LASSO and random forest modeling. On univariate analysis mean and max dose to multiple regions of the corpus callosum (CC) were correlated with attention/processing speed decline; most significantly in WAIS coding, including Dmax to the anterior CC (p = 0.011) and central CC (p = 0.010), and Dmax and Dmean to the mid anterior CC (p = 0.006 and 0.010). Mean dose to the left fornix was associated with decline in memory (p = 0.023, cutoff 12.9 Gy), as were increasing age and both concurrent and adjuvant chemotherapy. On multivariate analysis for attention, automated bootstrapped logistic regression showed the most frequently selected variable was mean dose to the mid anterior CC. Performance at nested cross-validation by AUC was 0.80 (0.75-0.84); LASSO model performance by AUC was 0.76 (0.72-0.81) with Dmean to the mid anterior CC being the most frequent variable. The top five most important variables in the Random Forest as ranked by mean decrease in Gini coefficient were mean dose to mid anterior CC, all white matter, combined CC and max dose to CC and posterior CC. Model performance by AUC was 0.66 (0.60-0.71). Here, we present the first, to our knowledge, NTCP model for decline in attention/processing speed, along with dosimetric predictors of memory decline beyond the hippocampus. We found that after partial brain RT, dose to several ROIs significantly correlated with post-RT impairment. These data can guide future cognitive-sparing strategies for brain RT.

Association of white matter hyperintensity accumulation with domain-specific cognitive decline: a population-based cohort study

We investigated the association of load and accumulation of white matter hyperintensities (WMHs) with rate of cognitive decline. This population-based study included 510 dementia-free people (age ≥60 years) who had repeated measures of global and regional (lobar, deep, periventricular) WMHs up to 6 years (from 2001–2003 to 2007–2010) and repeated measures of cognitive function (episodic memory, semantic memory, category fluency, letter fluency, executive function, perceptual speed) up to 15 years (from 2001–2004 to 2016–2019). We found that greater baseline loads of global and regional WMHs were associated with faster decline in letter fluency, perceptual speed, and global cognition. Furthermore, faster accumulation of global, deep, and periventricular WMHs was related to accelerated cognitive decline, primarily in perceptual speed. These data show that WMHs are associated with decline in perceptual speed rather than episodic or semantic memory and that cognitive change is more vulnerable to WMH accumulations in deep and periventricular regions.

Plasma phosphorylated tau-217 exhibits sex-specific prognostication of cognitive decline and brain atrophy in cognitively unimpaired adults.

Accumulating evidence indicates disproportionate tau burden and tau-related clinical progression in females. However, sex differences in plasma phosphorylated tau (p-tau)217 prediction of subclinical cognitive and brain changes are unknown. We measured baseline plasma p-tau217, glial fibrillary acidic protein (GFAP), and neurofilament light (NfL) in 163 participants (85 cognitively unimpaired [CU], 78 mild cognitive impairment [MCI]). In CU, linear mixed effects models examined sex differences in plasma biomarker prediction of longitudinal domain-specific cognitive decline and brain atrophy. Cognitive models were repeated in MCI. In CU females, baseline plasma p-tau217 predicted verbal memory and medial temporal lobe trajectories such that trajectories significantly declined once p-tau217 concentrations surpassed 0.053 pg/ml, a threshold that corresponded to early levels of cortical amyloid aggregation in secondary amyloid positron emission tomography analyses. CU males exhibited similar rates of cognitive decline and brain atrophy, but these trajectories were not dependent on plasma p-tau217. Plasma GFAP and NfL exhibited similar female-specific prediction of medial temporal lobe atrophy in CU. Plasma p-tau217 exhibited comparable prediction of cognitive decline across sex in MCI. Plasma p-tau217 may capture earlier Alzheimer's disease (AD)-related cognitive and brain atrophy hallmarks in females compared to males, possibly reflective of increased susceptibility to AD pathophysiology.

Participant-specific interrogation of population-based data to predict cognitive decline from neuropsychiatric symptoms and neuroimaging biomarkers: A machine learning approach (P12-6.001)

<h3>Objective:</h3> Develop machine learning (ML) models to predict decline in global cognition and attention from neuroimaging biomarkers of Alzheimer’s disease (AD) and neuropsychiatric symptoms (NPS). <h3>Background:</h3> ML is increasingly being used in brain aging research. <h3>Design/Methods:</h3> We developed four ML models (support vector machine, Gaussian process, random forest, Naïve Bayes) to predict z-scored global cognition and attention domain changes between first and last study visits of each participant. We used a stepwise approach to develop the prediction models by: 1) including AD biomarkers (PiB- &amp; FDG-PET), education, and APOE ɛ4 status; followed by 2) adding measures of depression (Beck Depression Inventory-II; BDI-II), and anxiety (Beck Anxiety Inventory; BAI); then 3) adding 12 NPS including NPS severity as measured by Neuropsychiatric Inventory Questionnaire (NPI-Q). <h3>Results:</h3> Data from 777 cognitively unimpaired (CU) participants for the outcome of global cognition z-score, and 795 CU participants for the outcome of attention z-score was available. 80% of the sample was randomly used to train the model, which was blind tested on the remaining 20%. For global cognition, the best model was able to predict 78% of participants with decreasing z-score using AD biomarkers, education, and APOE ɛ4 status. Adding BDI-II and BAI improved the prediction to 87%; and adding 12 NPS further improved the prediction to 96% of participants with decreasing z-scores. Including NPS severity did not improve the model’s performance. For the attention domain, the best model predicted 89% of participants with decreasing z-score using AD biomarkers, education, and APOE ɛ4 status. After adding BDI-II and BAI measurements, the model was able to predict 97% of participants with decreasing z-scores. Adding 12 NPS, and NPI severity only marginally improved the model’s performance to 98%. <h3>Conclusions:</h3> ML has the potential to successfully predict global and domain-specific cognitive decline in community-dwelling persons, with NPS improving prediction compared to AD neuroimaging biomarkers alone. <b>Disclosure:</b> Mr. Shah has nothing to disclose. Jeremy Syrjanen has nothing to disclose. Dr. Krell-Roesch has nothing to disclose. The institution of Walter Kremers has received research support from Biogen. Dr. Vemuri has received personal compensation in the range of $500-$4,999 for serving on a Speakers Bureau for Miller Medical Communications Inc.. The institution of Dr. Vemuri has received research support from NIH. The institution of Dr. Vassilaki has received personal compensation in the range of $5,000-$9,999 for serving as a Consultant for F. Hoffmann-La Roche Ltd . Dr. Vassilaki has stock in Abbott Laboratories. Dr. Vassilaki has stock in Johnson and Johnson. Dr. Vassilaki has stock in Medtronic. Dr. Vassilaki has stock in Amgen. Dr. Vassilaki has stock in AbbVie. Dr. Vassilaki has stock in Merck. The institution of Dr. Vassilaki has received research support from NIH. The institution of Dr. Vassilaki has received research support from European Union/ St. Anne’s University Hospital Brno, Czech Republic. The institution of an immediate family member of Dr. Vassilaki has received research support from Avobis Bio, LLC. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Roche. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Merck. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Genentech. Dr. Petersen has received personal compensation in the range of $500-$4,999 for serving as a Consultant for Nestle. Dr. Petersen has received personal compensation in the range of $5,000-$9,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Genentech, Inc.. Dr. Petersen has received personal compensation in the range of $10,000-$49,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Roche, Inc.. Dr. Petersen has received publishing royalties from a publication relating to health care. Dr. Petersen has received publishing royalties from a publication relating to health care. The institution of Dr. Forzani has received research support from NIH. The institution of Dr. Forzani has received research support from NSF. Dr. Forzani has received intellectual property interests from a discovery or technology relating to health care. Dr. Forzani has received personal compensation in the range of $100,000-$499,999 for serving as a Professor with Arizona State University. Dr. Wu has nothing to disclose. The institution of Dr. Geda has received research support from NIH.

Association of primary lifetime occupational cognitive complexity and cognitive decline in a diverse cohort: Results from the KHANDLE study.

Higher occupational complexity has been linked to favorable cognitive outcomes, but rarely examined in racially and ethnically diverse populations. In a diverse cohort (n=1536), linear mixed-effects models estimated associations between main lifetime occupational complexity and domain-specific cognitive decline (z-standardized). Occupational complexity with data, people, and things were classified using the Dictionary of Occupational Titles. For occupational complexity with data, highest tertile (vs. lowest) was associated with higher baseline executive function (β=0.11; 95% confidence interval [CI] 0.00-0.22) and slower annual rate of decline (β=0.03; 95% CI 0.01-0.06), and higher baseline semantic memory (β=0.14; 95% CI 0.04-0.25). Highest tertile of occupational complexity with people was associated with higher baseline executive function (β=0.29; 95% CI 0.18-0.40), verbal episodic memory (β=0.12; 95% CI 0.00-0.24), and semantic memory (β=0.23; 95% CI 0.12-0.34). In a diverse cohort, higher occupational complexity is associated with better cognition. Findings should be verified in larger cohorts. Few studies have examined associations of occupational complexity with cognition in diverse populations. Racial and ethnic minorities are disproportionately exposed to lower occupational complexity. Occupational complexity with data and people are associated with better cognition.

A Longitudinal Study of Acculturation in Context and Cardiovascular Health and Their Effects on Cognition Among Older Latino Adults.

Background We previously outlined the importance of considering acculturation within the context of older Latino adults'lived experience (ie, acculturation in context) to better capture contributors to cognitive aging. We now examine this conceptual framework as related to level of and change in cardiovascular health, and whether cardiovascular health modifies previously documented associations of acculturation in context with cognition. Methods and Results Acculturation in context data from 192 Latino participants without dementia at baseline (age ~70 years) were compiled into 3 separate composite scores: acculturation-related (nativity, language-, and social-based preferences), contextually related socioenvironmental (experiences of discrimination, social isolation, social networks), and familism-related (Latino-centric family ethos). A modified American Heart Association's Life's Simple 7 (mLS7; ie, smoking, physical activity, body mass index, blood pressure, total cholesterol, blood glucose) was used to measure cardiovascular health. Mixed effects regressions simultaneously tested the association of all 3 composite scores with total mLS7 adjusting for confounders. Separate models tested whether mLS7 modified associations of the 3 composite scores and cognition. The contextually related socioenvironmental composite score reflecting higher discrimination, higher social isolation, and smaller social networks (estimate=0.22, SE=0.10, P=0.02) and the familism score (estimate=0.16, SE=0.07, P=0.02) both significantly associated with change in total mLS7. The acculturation-related composite was not significantly associated with change in mLS7. No composite was significantly associated with level of mLS7. Total mLS7, however, significantly modified associations between the acculturation-related composite and change in working memory (estimate=-0.02, SE=0.01, P=0.043). Conclusions Acculturation within the context of older Latino adults' lived experience is important for maintaining cardiovascular health, relationships that also affect domain-specific cognitive decline.

Trauma Across the Life Span and Multisystem Morbidity in Women With HIV.

Sexual and physical abuse are highly prevalent among women living with HIV (WLWH) and are risk factors for the development of mental health and substance use disorders (MHDs, SUDs), and cognitive and medical comorbidities. We examined empirically derived patterns of trauma, MHD, and SUD, and associations with later cognitive and health outcomes. A total of 1027 WLWH (average age = 48.6 years) in the Women's Interagency HIV Study completed the World Mental Health Composite International Diagnostic Interview from 2010 to 2013 to identify MHDs, SUDs, and age at onset of sexual and physical abuse. Then, cognitive impairment, cardiovascular/metabolic conditions, and HIV disease outcomes were assessed for up to 8.8 years. Latent class analysis identified patterns of co-occurring trauma, MHDs, and/or SUDs. Generalized estimating equations determined associations between these patterns and midlife cognitive and medical outcomes. Six distinct profiles emerged: no/negligible sexual/physical trauma, MHD, or SUD (39%); preadolescent/adolescent sexual trauma with anxiety and SUD (22%); SUD only (16%); MHD + SUD only (12%); early childhood sexual/physical trauma only (6%); and early childhood sexual/physical trauma with later MHD + SUD (4%). Profiles including early childhood trauma had the largest number of midlife conditions (i.e., cognitive, cardiovascular, HIV-related). Preadolescent/adolescent sexual trauma with anxiety and SUD predicted both global and domain-specific cognitive declines. Only SUD without trauma predicted lower CD4, whereas childhood trauma with MHD + SUD predicted increased CD8. WLWH have complex multisystem profiles of abuse, MHD, and/or SUD that predict midlife cognitive, metabolic/cardiovascular, and HIV outcomes. Understanding the interplay between these factors over time can identify risks and personalize preventative and treatment interventions.

Association between carotid intima-media thickness and cognitive decline differs by race.

Common carotid intima-media thickness (cIMT) is a marker of subclinical atherosclerosis and is associated with cognitive decline. Although carotid atherosclerosis is more frequent in White than in Black participants, little is known whether race modifies the association between cIMT and cognitive decline. In this longitudinal analysis of the ELSA-Brasil, we assessed cIMT using ultrasound and cognitive performance using different domain tests. We used linear mixed models, interaction analysis, and race stratified analyses. Baseline high IMT values were associated with memory (p<0.001), verbal fluency (p<0.001), TMT-B (p<0.001)), and global cognitive decline (p<0.001). Race was an effect modifier in the association between IMT and global cognitive decline (0.043), with stronger association in White (p<0.001) than in Black (p=0.009) participants. Baseline IMT was associated with global and domain-specific cognitive decline and race modified this relationship, with stronger associations in White participants. Carotid intima-media thickness (cIMT) was associated with cognitive decline. cIMT and cognitive decline association was stronger in White than in Black participants. We used inverse probability weighting to address attrition bias.

Hippocampal, basal ganglia and olfactory connectivity contribute to cognitive impairments in Parkinson's disease.

Cognitive impairment is increasingly recognized as a characteristic feature of Parkinson's disease (PD), yet relatively little is known about its underlying neurobiology. Previous investigations suggest that dementia in PD is associated with subcortical atrophy, but similar studies in PD with mild cognitive impairment have been mixed. Variability in cognitive phenotypes and diversity of PD symptoms suggest that a common neuropathological origin results in a multitude of impacts within the brain. These direct and indirect impacts of disease pathology can be investigated using network analysis. Functional connectivity, for instance, may be more sensitive than atrophy to decline in specific cognitive domains in the PD population. Fifty-eight participants with PD underwent a neuropsychological test battery and scanning with structural and resting state functional MRI in a comprehensive whole-brain association analysis. To investigate atrophy as a potential marker of impairment, structural gray matter atrophy was associated with cognitive scores in each cognitive domain using voxel-based morphometry. To investigate connectivity, large-scale networks were correlated with voxel time series and associated with cognitive scores using distance covariance. Structural atrophy was not associated with any cognitive domain, with the exception of visuospatial measures in primary sensory and motor cortices. In contrast, functional connectivity was associated with attention, executive function, language, learning and memory, visuospatial, and global cognition in the bilateral hippocampus, left putamen, olfactory cortex, and bilateral anterior temporal poles. These preliminary results suggest that cognitive domain-specific networks in PD are distinct from each other and could provide a network signature for different cognitive phenotypes.

Reproductive Markers in Alzheimer's Disease Progression: The Framingham Heart Study.

Reproductive status, such as the age of menarche or menopause, may be linked to cognitive abilities and risk for incident Alzheimer's disease (AD) but the evidence is conflicting. It is also not fully known if these factors interact with cortical beta-amyloid deposition. To study the relationship between reproductive risks, sex hormone markers and risk for decline in specific cognitive domains in women. We analyzed the association of reproductive markers (age at menarche, number of births, age at menopause, sex hormone-binding globulin, estradiol, estrone, total testosterone, free testosterone) with incident AD and annualized cognitive decline in the community-based longitudinal Framingham Heart Study (FHS) Offspring women 60 years and older (n=772, mean age 68 years, mean follow-up 10.7 ± 3 years). We used the Cox proportional hazards regression model and linear regression model, adjusting for covariates. Incident AD dementia as well as the annualized change in memory, language, attention and executive functions. Older age at menopause was associated with a lower risk of incident AD dementia (p = 0.047, 6% lower risk per older year) after adjusting for baseline age, education, hormone therapy status, and MMSE score. Older age at menopause was significantly associated with a slower annualized decline in memory (beta = 0.085, p = 0.00059). The lower level of plasma Aβ42 was also associated with a higher risk of incident AD (HR = 0.97, 95% CI = 0.95, 0.99; p = 0.0039) but there was no significant interaction effect with age at menarche, age at menopause or plasma sex hormone levels. Younger age at menopause is a risk factor for late-life memory decline and incident AD. This risk appears to be independent of Aβ42 pathology. Further studies to understand the biological and social mechanisms underlying the differential effects of reproductive risks are warranted.