Differences In Cognitive Decline Research Articles

Biological sex alters the association between cerebral pulsatility and hippocampal volume in cognitively unimpaired adults

Cerebrovascular dysregulation with age contributes to cognitive decline. Age-related changes in intracranial blood flow and cerebral pulsatility are linked with adverse structural changes including white matter hyperintensities. The hippocampus represents a key area for cognition and demonstrates rapid deterioration in the early stages of Alzheimer’s disease. Yet the impact of intracranial blood flow and cerebral pulsatility on hippocampal deterioration in cognitively unimpaired adults remains unclear. Importantly, age-related changes in intracranial blood flow and cerebral pulsatility differ by sex. Therefore, this study tested the hypothesis that intracranial blood flow is positively associated with hippocampal volume, while cerebral pulsatility is negatively associated with hippocampal volume and that the associations would differ by sex. Cognitively unimpaired adults (388 total, 263 females, 64 ± 8 years of age) completed 3T magnetic resonance imaging (MRI). Hippocampal volume (mm3) was normalized to intracranial volume and evaluated from T1-weighted images. Intracranial blood flow (mL/min) and cerebral pulsatility (maximum flow − minimum flow/mean flow; a.u.) were evaluated in the internal carotid arteries (ICA), middle cerebral arteries (MCA), and basilar artery from 4D flow MRI. All data are reported for the left side of the brain. Age was negatively associated with hippocampal volume and similar relationships were observed in males (β = -16 ± 3, P < 0.01) and females (β = -17 ± 2, P < 0.01). As such, age was included as a covariate in all models. Blood flow in the ICA, MCA, and basilar artery was not associated with hippocampal volume (all P > 0.37) and there were no flow-by-sex interactions (all P > 0.19). In contrast, cerebral pulsatility was negatively associated with hippocampal volume in a sex and vessel specific manner. ICA pulsatility was associated with hippocampal volume (P = 0.03, β = -183 ± 83) and the relationship did not differ by sex (pulsatility-by-sex interaction: P = 0.19). Basilar artery pulsatility was associated with hippocampal volume in a sex-specific manner (pulsatility-by-sex interaction: P < 0.01) such that there was an association in females (β = -346 ± 63, P < 0.01) but not males (β = 60 ± 92, P = 0.51). A sex-specific relationship (pulsatility-by-sex interaction: P < 0.01) was also observed between MCA pulsatility and hippocampal volume (females: β = -180 ± 54, P < 0.01; males: β = 1 ± 136, P = 0.99). Therefore, elevated cerebral pulsatility is linked with hippocampal deterioration in a sex and vessel specific manner. These findings may provide insights into sex differences in cognitive decline with age and the development of Alzheimer’s disease. This research was funded by NIH grants (R03 AG070469-01 and R03 AG070469-S1; JNB), a Virginia Horne Henry Research Grant (JNB), and a Wisconsin Alzheimer's Disease Research Center Grant (P30-AG062715). This is the full abstract presented at the American Physiology Summit 2024 meeting and is only available in HTML format. There are no additional versions or additional content available for this abstract. Physiology was not involved in the peer review process.

Sex differences in cognitive decline among middle-aged and older adults: a cohort study in Europe.

Previous studies on sex differences in cognitive decline provide inconsistent findings, with many European countries being underrepresented. We determined the association between sex and cognitive decline in a sample of Europeans and explored differences across birth cohorts and regions. Participants 50+ years old enrolled in the Survey of Health, Ageing and Retirement in Europe had their cognition measured by tests of immediate recall, delayed recall and verbal fluency biennially up to 17years of follow-up (median 6, interquartile range 3-9years). We used linear mixed-effects models to assess the relationship between sex and the rate of cognitive decline, adjusting for sociodemographic and health-related characteristics. Of 66,670 participants (mean baseline age 63.5 ± standard deviation 9.4), 55% were female. Males and females had similar rates of decline in the whole sample in immediate recall (beta for interaction sex × time B = 0.002, 95% CI -0.001 to 0.006), delayed recall (B = 0.000, 95% CI -0.004 to 0.004), and verbal fluency (B = 0.008, 95% CI -0.005 to 0.020). Females born before World War II had a faster rate of decline in immediate recall and delayed recall compared to males, while females born during or after World War II had a slower rate of decline in immediate recall. Females in Central and Eastern Europe had a slower rate of cognitive decline in delayed recall compared to males. Our study does not provide strong evidence of sex differences in cognitive decline among older Europeans. However, we identified heterogeneity across birth cohorts and regions.

SEX AND RACE/ETHNIC DIFFERENCES IN TERMINAL COGNITIVE DECLINE

Abstract Background Cognitive decline has been documented in older adults, but sex and racial/ethnic differences among decedents have not been studied. Here we investigate the relation of mortality to change in the cognitive function of older individuals by sex and race/ethnicity. Methods The study analyzed data from the Health and Retirement Study (HRS) between 1993 and 2018, which included information on total word recall, mental status, and total cognition of individuals aged 65 and older. The study estimated the loss of cognitive function using a multilevel random coefficient model, considering sex and racial/ethnic differences in the risk of death, age, and death status. The study also approximated terminal cognitive decline using cognitive scores reported within two years before death for decedents. Results On average, older women performed better than older men in word recall and overall cognition, while older White Americans performed better than African Americans and Hispanics/Latinos in overall cognition at all ages. Decedents had a similar cognitive function to survivors at age 65, but their cognition declined quickly with age, especially among older women and White Americans. Evidence of terminal cognitive decline within two years before death was significant regardless of age but less conclusive for African Americans and Hispanics/Latinos due to smaller sample sizes. Conclusions This paper indicated evidence of sex and race/ethnic differences in cognitive decline and terminal cognitive decline among older adults, which may have critical clinical implications directly linked to the onset and duration of dementia risk.

Utility of Baseline Pathological, Neuroimaging and Clinical Markers for Progression Prognosis and Subtype Classification in Early Parkinson’s Disease: Implications for Cognitive Impairment

AbstractBackgroundCognitive dysfunction is a well‐recognised PD symptom, but it is highly heterogenous and under‐assessed clinically. Interestingly, PD motor subtypes are associated with different risk of cognitive decline. However, subtype classification is currently reliant on subjective clinician assessment and may consequently be misdiagnosed. Therefore, objective biomarkers of PD progression are critically needed, but must be validated prior to clinical deployment. We assessed the utility of various clinical, neuroimaging and pathological measures as predictors of cognitive outcomes up to 5‐years follow‐up in early PD.MethodData was extracted from the Parkinson’s Progression Markers Initiative. Cognitive assessments were compiled into an overall cognition score via principal component analysis. Distinct subgroups were identified via Fuzzy C‐Means clustering on Year‐5 Unified Parkinson’s Disease Rating Scale (UPDRS) motor scores. Models predicting cluster membership were created via logistic regression and a stratified cross‐validation machine learning pipeline, comparing two predictor inputs: 1) baseline motor assessments; and 2) incorporating additional measures, including prodromal assessments (sleep, olfactory and autonomic function), neuroimaging (proxy SN volume, striatal DaT binding) and biofluid markers (CSF alpha‐syn, p‐tau, a‐beta, and serum IGF‐1) at baseline. Finally, cluster membership was used for retroactive assessment of baseline and follow‐up cognitive data.ResultsTwo clusters were identified, with cluster two (n = 117) demonstrating higher rigidity, lower DaT binding, worsened motor outcomes and increased mood dysfunction at follow‐up compared to tremor‐dominant cluster one (n = 183). Additionally, rigid‐dominant membership was predicted by male sex, higher p‐tau, along with lower a‐beta, predicting 40% of variance (n = 111). This was significantly higher (P<0.001) than baseline motor scores alone, only accounting for 18% of variance. This was supported by machine learning, whereby incorporating additional assessments corresponded to a classification accuracy of 62%, compared to 26% when omitted. Finally, higher probability of belonging to the rigid‐dominant cluster yielded significant negative correlations cognition at baseline and follow‐up.ConclusionIncreased likelihood of rigid‐dominance corresponded to more profound cognitive decline, which may in part result from neuropathological marker concentrations as highlighted by predictive models. Therefore, further tracking of this cohort, specifically conversion into MCI or dementia, could provide insight into pathological contribution to differences in cognitive decline between PD subtypes.

Age‐ and sex‐dependent differences in cognitive decline in rat models of Alzheimer’s disease

AbstractBackgroundMemory loss has been a central focus of Alzheimer’s disease (AD) research but executive dysfunction may be one of the earliest indicators of AD (Baudic et al., 2006). Executive function refers to a group of cognitive processes that are required for goal directed behaviours, such as working memory and cognitive flexibility. Amyloid‐β (Aβ) plaques and neurofibrillary tangles are considered the pathological hallmarks of AD, but evidence suggests that these are not the earliest pathologies to appear in the AD brain (Sperling et al., 2011). This highlights the importance of assessing both the prodromal and more advanced phases of AD in preclinical modelling. This study aimed to characterize age‐ and sex‐related changes in executive function, learning, and memory across normal aging in rats as well as in two aging transgenic rat strains of AD: TgAPP21 (Aβ plaque‐negative) and TgAPP/PS1 (Aβ plaque‐positive).MethodMale and female wildtype Fischer 344, TgAPP21, and TgAPP/PS1 rats were used in this study. The TgAPP21 rat overexpresses the mutant human amyloid precursor protein but does not spontaneously develop Aβ plaques, serving as an important model of prodromal AD. The TgAPP/PS1 rat overexpresses mutant human forms of both the amyloid precursor protein and Presenilin‐1 and does develop age‐dependent Aβ plaques. These strains allowed us to assess cognition under three conditions (i) normal aging, (ii) increased Aβ without plaque deposition, and (iii) age‐dependent Aβ plaque deposition. At 3, 9, or 15 months of age the rats were tested for spatial learning and memory, working memory, and cognitive flexibility using the Morris water maze, the 8‐arm radial water maze, and a T‐maze set‐shifting task.ResultAge‐dependent cognitive decline was observed across all genotypes but was exacerbated in both transgenic models. Effects of age, sex, and genotype varied across the cognitive tasks, emphasizing the importance of assessing multiple cognitive domains.ConclusionThese findings expand our understanding of the roles of sex, age and Aβ plaque‐positive/negative environments in cognitive decline in preclinical rat strains of AD. Overall, this work supports further investigation into the pathologies driving these cognitive changes and potential biomarkers for earlier detection.

A polygenic risk score (PRS) predicts cognitive decline in the APOE3 population in an early Alzheimer’s disease clinical trial cohort

AbstractBackgroundAlzheimer’s disease (AD) is one of the most common forms of dementia globally and is defined by accumulation of extracellular amyloid plaques and intracellular tau‐containing neurofibrillary tangles in neuronal cells. These pathological changes occur more than a decade prior to symptom onset. Given that disease modifying therapies are geared towards asymptomatic/early AD patients, identification of asymptomatic individuals at risk of progression is key. Genome‐Wide Association Studies(GWAS) for AD have implicated many single nucleotide polymorphisms (SNPs) associated with disease risk. Whereas a minority of early onset AD cases are driven by mutations in genes, sporadic AD cases have complex genetic architecture and are highly heritable. Polygenic Risk Scores (PRS), which aggregate genome‐wide risk loci, have been shown to predict AD onset with AUCs of 75‐84%.MethodsThe PRS approach used in this study is built from a sum of weighted contributions of over 100,000s SNPs associated with disease. We utilized PRS (genoSCORE™) to predict cognitive function decline in a cohort of 280 AD patients in a Ph2 clinical trial for Tilavonemab, a monoclonal antibody targeting the N‐terminus of human tau. Additionally, genoTOR™ was calculated to identify pathways most impacted by the genetic variants enriched in the cohort.ResultsGiven that tilavonemab did not alter Clinical Dementia Rating‐Sum of Boxes(CDR‐SB), we tested differences in cognitive decline between high PRS and low PRS individuals defined using a threshold of 0.6 in the entire cohort and found no difference. Upon stratification by APOE status, higher PRS(> = 0.6) predicted an increase in CDR‐SB of an average of 1.0 at week 72 (p<0.1) and week 96 (p<0.05) compared to participants with lower PRS(<0.6) within the APOE3 population. Additional analyses of the genoTOR™ signaling pathways are ongoing.ConclusionsThe results of these analyses demonstrate that genoSCORE™ may be helpful to enrich for APOE3 individuals most susceptible to cognitive decline over time. Since the majority of genetic risk studies have focused on an APOE4 population, this method provides a novel tool to enrich for individuals at high risk for cognitive decline over time in a less studied population in which there is difficulty with prediction of disease progression.

Cognitive decline among older adults with depressive symptoms before and during the COVID-19 pandemic

BackgroundWhether the COVID-19 pandemic would induce accelerated cognitive decline in individuals with depressive symptoms is undetermined. ObjectiveTo investigate the impact of the COVID-19 pandemic on cognitive function among older adults with depressive symptoms. MethodsData were from the Health and Retirement Study. The interval between wave 13 and wave 14 was defined as the prepandemic period, and the interval between wave 14 and wave 15 was defined as the pandemic period. Linear mixed models and modified Poisson regression models were employed to compare the differences in cognitive decline and incident dementia between participants with and without depressive symptoms before and during the pandemic. ResultsA total of 9304 participants were included. During the prepandemic period, no significant difference was observed in changes in cognitive scores between participants with and without depressive symptoms. During the pandemic period, an accelerated decline in cognitive scores was found between the two groups (global cognition: -0.25, 95 % CI: −0.41 to −0.08, P = 0.004; memory: -0.16, 95 % CI: −0.31 to −0.02, P = 0.030; executive function: -0.08, 95 % CI: −0.15 to −0.02, P = 0.014). Participants with depressive symptoms had a higher risk of developing dementia during the pandemic (RR: 1.48, 95 % CI: 1.17 to 1.88, P < 0.001). LimitationsCausal relationship cannot be concluded due to the observational study design. ConclusionsOlder adults with depressive symptoms suffered more severe cognitive deterioration and had a higher risk of incident dementia during the pandemic, underscoring the need to provide cognitive monitoring and interventions for those with depressive symptoms during the COVID-19 pandemic.

Type 2 Diabetes Comorbidity and Cognitive Decline in Patients with Alzheimer's Disease.

Although insulin dysregulation and resistance likely participate in Alzheimer's disease (AD) etiologies, little is known about the correlation between type 2 diabetes mellitus (T2DM) and the progression of cognitive decline in patients with AD. To determine whether AD patients with T2DM experience more rapid cognitive decline than those without T2DM. All cognitive performance data and the presence or absence of T2DM comorbidity in patients with AD were derived from the US National Alzheimer's Coordinating Center's (NACC) Uniform Data Set (UDS). A search of the UDS identified 3,055 participants with AD who had more than one epoch completed. The data set culled clinically diagnosed AD dementia patients who were assessed for diabetes type identified during at least 1 visit. These patients were divided into 2 groups based on whether they had a diagnosis of T2DM. The data from these groups were then analyzed for differences in cognitive decline based on neuropsychological test battery scores and a Clinician Dementia Rating using a general linear model. Comparisons of the mean scores for 16 selected tests from the neuropsychological test battery showed no significant differences in baseline scores and scores at subsequent visits between the T2DM and nondiabetic groups. The results revealed no differences in cognitive decline metrics over the course of 5 visits in either study group. These data indicate that the presence of T2DM does not increase the rate of cognitive decline in AD. This finding contradicts expected disease burden and will need to be explored further.

The Effects of Midlife Acute and Chronic Stressors on Black-White Differences in Cognitive Decline.

Midlife stressors may be particularly consequential for cognitive performance and disparities in cognitive decline. This study examined Black-White differences in trajectories of cognition among middle-aged adults and the effects of acute and chronic stressors on these trajectories. Data come from 4,011 cognitively healthy individuals aged 51-64 (620 Black and 3,391 White) who participated in the 2006-2018 waves of the Health and Retirement Study. Stressors included a count of recent life events and measures of financial strain and everyday discrimination. Global cognition was assessed using a modified version of the Telephone Interview for Cognitive Status. Linear mixed models with random slopes and intercepts assessed change in cognition over time. Race-by-time, race-by-stressor, time-by-stressor, and race-by-stressor-by-time interactions were assessed as were quadratic terms for time and each stressor. After adjusting for sociodemographic, health behaviors, and health-related factors, Black respondents had lower initial cognitive performance scores (b = -1.75, p < .001) but experienced earlier but slower decline in cognitive performance over time (Black × Time2 interaction: b = 0.02, p < .01). Financial strain, discrimination, and recent life events each had distinct associations with cognitive performance but did not influence racial differences in levels of or change in cognition over time. Middle-aged Black adults have lower initial cognition levels and experience earlier but less accelerated cognitive decline compared to White middle-aged adults. Midlife acute and chronic stressors influence baseline cognition but do so in different ways. Future research should examine the influence of other stressors on racial differences in cognitive decline at other points in the life course.

Sex differences in microglia function in aged rats underlie vulnerability to cognitive decline

Aging is associated with a significant shift in immune system reactivity (“inflammaging”), as basal inflammation increases but protective responses to infection are compromised. The immune system exhibits considerable sex differences, which may influence the process of inflammaging, including immune cell activation and behavioral consequences of immune signaling (i.e., impaired memory). Here, we test the hypothesis that sex differences in immune aging may mediate sex differences in cognitive decline. Aged male and female rats received peripheral immune stimulation using lipopolysaccharide (LPS), then molecular, cellular, and behavioral outcomes were assessed. We observed that LPS-treated aged male rats showed cognitive impairment and increased neuroinflammatory responses relative to adult males. In contrast, aged female rats did not display these aging-related deficits. Using transcriptomic and flow cytometry analyses, we further observed significant age- and sex- dependent changes in immune cell populations in the brain parenchyma and meninges, indicating a broad shift in the neuroinflammatory environment that may potentiate these behavioral effects. Ovariectomized aged female rats were also resistant to inflammation-induced memory deficits, indicating that ovarian hormones are not required for the attenuated neuroinflammation in aged females. Overall, our results indicate that males have amplified inflammatory priming with age, which contributes to age-associated cognitive decline. Our findings highlight sexual dimorphism in mechanisms of aging, and suggest that sex is a crucial consideration for identifying therapies for aging and neuroinflammation.

Sex differences for cognitive decline in progressive supranuclear palsy

IntroductionCognitive dysfunction is a core clinical feature of progressive supranuclear palsy (PSP), with executive function being most markedly affected. In other neurodegenerative conditions, such as Alzheimer's and Parkinson's diseases, there are a growing number of reports demonstrating that cognition is differentially impacted in men and women. In PSP, however, the sex differences in cognitive decline have yet to be fully characterized. MethodsData were obtained from the TAUROS trial for 139 participants with mild-to-moderate PSP (62 women, 77 men). Sex differences in longitudinal change in cognitive performance were evaluated with linear mixed models. Exploratory subgroup analyses assessed whether sex differences varied by baseline executive dysfunction, PSP phenotype, or baseline age. ResultsIn the primary whole group analyses, there were no sex differences for change in cognitive performance. Among participants with normal executive function at baseline, men declined more severely on executive function and language tests. Among the PSP-Parkinsonism subgroup, men declined more severely on category fluency. Across people aged≥65, men had a worse decline on category fluency, whereas across people aged <65, women had a worse decline on DRS construction. ConclusionIn people with mild-to-moderate PSP, there are no sex differences in cognitive decline. However, the rate of cognitive decline may differ for women and men based on the level of baseline executive dysfunction, PSP-phenotype and age. Further studies are needed to clarify how sex differences in PSP clinical progression vary by disease stage and to examine the contributions of co-pathology to these observed sex differences.

Sex Differences for Verbal Fluency Decline in Progressive Supranuclear Palsy (P8-11.003)

<h3>Objective:</h3> To assess for sex differences in longitudinal change in verbal fluency performance in people with progressive supranuclear palsy (PSP). <h3>Background:</h3> Cognitive impairment is a core feature of PSP; executive dysfunction and reduced phonemic verbal fluency are included in the diagnostic criteria. Sex differences in other neurodegenerative disorders, such as Alzheimer’s and Parkinson’s diseases, have been extensively studied with reports consistently showing cognition is differentially impacted in men and women. In PSP, however, the sex differences in cognitive decline have yet to be fully characterized. <h3>Design/Methods:</h3> We included 139 participants with PSP (62 women, 77 men) that underwent cognitive testing as part of the Tauros trial. Baseline sex differences in demographics and verbal fluency performance were assessed using Mann-Whitney U tests. Then, sex differences in longitudinal change in verbal fluency performance were evaluated with linear mixed models, including interactions of time and baseline score, age, and education as covariates. <h3>Results:</h3> There were no significant differences in baseline age, disease duration, and disease severity between women and men. Men had significantly more education than women (<i>p</i>=0.03). Baseline verbal fluency performance was similar across the sexes. However, compared to women, men had more severe decline in semantic fluency (β=−3.95±0.98; <i>p</i>=7.26e-5) and lexical fluency over time (β=−1.64±0.76; <i>p</i>=0.031). <h3>Conclusions:</h3> We found that men with PSP had worse decline in verbal fluency performance than women, suggesting PSP may affect cognition differently between sexes. Although studies in healthy elderly show a more pronounced decline in category fluency than letter fluency, our findings were likely not due to aging as these studies in healthy elderly report no sex differences for category fluency performance or rate of decline. As cognitive impairment is common and burdensome in PSP, sex-specific approaches may be needed to address the needs of people with PSP. <b>Disclosure:</b> Mr. Digma has nothing to disclose. Dr. Quijano has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Novartis. Dr. Litvan has received personal compensation in the range of $500-$4,999 for serving on a Scientific Advisory or Data Safety Monitoring board for Lundbeck. Dr. Litvan has received personal compensation in the range of $10,000-$49,999 for serving as an Editor, Associate Editor, or Editorial Advisory Board Member for Frontiers in Neurology. Dr. Bayram has nothing to disclose.

Does the presence of type II Diabetes affect cognitive decline in Alzheimer’s Disease Dementia?

AbstractBackgroundAlzheimer’s disease (AD) is sometimes referred to as Type 3 diabetes. While it is very likely that insulin dysregulation and resistance participate in the etiology of AD pathologies, little is known about the possible correlation between diabetes and the progression of cognitive decline in AD patients. Previous studies have shown an increased risk of developing AD in patients with type 2 diabetes mellitus (T2DM). The specific aim of our study was to determine whether differences exist in cognitive decline experienced by AD subjects with and without T2DM co‐morbidity.MethodAll cognitive performance data and the presence or absence of T2DM co‐morbidity in AD patients used in the present report were derived from the Uniform Data Set (UDS) of the database maintained by the National Alzheimer’s Coordinating Center (NACC), USA. The scanning of the UDS database identified 3055 participants with AD who had more than one epoch completed. The dataset culled clinically‐diagnosed AD patients who were assessed for diabetes type in form A5 or D2 during at least one visit. These patients were divided into two groups dependent upon the presence of a diagnosis of T2DM. The data from these groups was then analyzed for differences in cognitive decline based upon Neuropsychological Battery Scores and a Clinician Dementia Rating (CDR) using a general linear model.ResultCognitive function tests looked at language, cognitive executive function, and verbal and nonverbal memory. Comparison of the mean scores in 16 selected tests from the Neuropsychological Battery test showed no significant differences in baseline scores and scores at subsequent visits between the T2DM and non‐diabetic groups.ConclusionUsing the NACC database, which receives longitudinal data from Alzheimer’s Disease research Centers (ADRCs), it was found that there were no differences in cognitive decline metrics over the course of 5 visits in either group. This supports the position that the presence of T2DM does not appear to increase the magnitude of cognitive decline in AD patients

A life course approach to understanding stress exposures and cognitive function among middle-aged and older adults

BackgroundMany studies have evaluated the stress-cognition association, but few have captured the cumulative nature of stress or distinguished the influences of stressors occurring in childhood versus adulthood. Using a lifecourse approach, we investigated whether cumulative stress exposures are associated with poorer cognitive function and faster cognitive decline. MethodsWe used data from the Midlife Development in the United States Study (N = 3,954, mean baseline age: 56 years). We fit marginal structural generalized estimating equations models to estimate the difference in baseline cognitive function per SD increment in the continuous stressor score, and, separately, between persons in each life course stressor profile and those who did not experience high stress in either childhood or adulthood. We also characterized differences in cognitive decline across levels of stress exposures. ResultsHigher cumulative stress exposure was associated with lower executive function (difference per SD in continuous stressor score = −0.12 SD units, 95% CI = −0.16, −0.08) and episodic memory (difference = −0.09 SD units, 95% CI = −0.13, −0.05). Baseline executive function and episodic memory were lower among those with high stress only in childhood, only in adulthood, and both, than among those without high stress in childhood or adulthood. There was little evidence that rate of change in executive function and episodic memory differed across levels of cumulative stress exposures. ConclusionsThese findings offer support to the hypothesis that stress exposures, accumulated over the life course, worsen cognitive performance, but limited support for the hypothesis that these exposures promote cognitive decline.

Blood Pressure and Later-Life Cognition in Hispanic and White Adults (BP-COG): A Pooled Cohort Analysis of ARIC, CARDIA, CHS, FOS, MESA, and NOMAS.

Ethnic differences in cognitive decline have been reported. Whether they can be explained by differences in systolic blood pressure (SBP) is uncertain. Determine whether cumulative mean SBP levels explain differences in cognitive decline between Hispanic and White individuals. Pooled cohort study of individual participant data from six cohorts (1971-2017). The present study reports results on SBP and cognition among Hispanic and White individuals. Outcomes were changes in global cognition (GC) (primary), executive function (EF) (secondary), and memory standardized as t-scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1 SD difference in cognition. Median follow-up was 7.7 (Q1-Q3, 5.2-20.1) years. We included 24,570 participants free of stroke and dementia: 2,475 Hispanic individuals (median age, cumulative mean SBP at first cognitive assessment, 67 years, 132.5 mmHg; 40.8% men) and 22,095 White individuals (60 years,134 mmHg; 47.3% men). Hispanic individuals had slower declines in GC, EF, and memory than White individuals when all six cohorts were examined. Two cohorts recruited Hispanic individuals by design. In a sensitivity analysis, Hispanic individuals in these cohorts had faster decline in GC, similar decline in EF, and slower decline in memory than White individuals. Higher time-varying cumulative mean SBP was associated with faster declines in GC, EF, and memory in all analyses. After adjusting for time-varying cumulative mean SBP, differences in cognitive slopes between Hispanic and White individuals did not change. We found no evidence that cumulative mean SBP differences explained differences in cognitive decline between Hispanic and White individuals.

Without Commitment to an Ontology, There Could Be No Causal Inference.

Without Commitment to an Ontology, There Could Be No Causal Inference.

Explanatory role of sociodemographic, clinical, behavioral, and social factors on cognitive decline in older adults with diabetes

BackgroundThe aim of the study was to examine the explanatory role of sociodemographic, clinical, behavioral, and social factors on racial/ethnic differences in cognitive decline among adults with diabetes.MethodsAdults aged 50+ years with diabetes from the Health and Retirement Survey were assessed for cognitive function (normal, mild cognitive impairment [MCI], and dementia). Generalized estimating equation (GEE) logistic regression models were used to account for repeating measures over time. Models were adjusted for sociodemographic (gender, age, education, household income and assets), behavioral (smoking), clinical (ie. comorbidities, body mass index), and social (social support, loneliness, social participation, perceived constraints and perceived mastery on personal control) factors.ResultsUnadjusted models showed non-Hispanic Blacks (NHB) and Hispanics were significantly more likely to progress from normal cognition to dementia (NHB OR: 2.99, 95%CI 2.35–3.81; Hispanic OR: 3.55, 95%CI 2.77–4.56), and normal cognition to MCI (NHB OR = 2.45, 95%CI 2.14–2.82; Hispanic OR = 2.49, 95%CI 2.13–2.90) compared to non-Hispanic Whites (NHW). Unadjusted models for the transition from mild cognitive decline to dementia showed Hispanics were more likely than NHW to progress (OR = 1.43, 95%CI 1.11–1.84).After adjusting for sociodemographic, clinical/behavioral, and social measures, NHB were 3.75 times more likely (95%CI 2.52–5.56) than NHW to reach dementia from normal cognition. NHB were 2.87 times more likely (95%CI 2.37–3.48) than NHW to reach MCI from normal. Hispanics were 1.72 times more likely (95%CI 1.17–2.52) than NHW to reach dementia from MCI.ConclusionClinical/behavioral and social factors did not explain racial/ethnic disparities. Racial/ethnic disparities are less evident from MCI to dementia, emphasizing preventative measures/interventions before cognitive impairment onset are important.

The Effects of Mid-life Stress Exposure on Black-White Differences in Cognitive Decline

Cognitive decline is a precursor to cognitive impairment and dementia. Recent research suggests that cognitive decline may begin earlier in the life course for Blacks and that Black-white disparities in cognitive function emerge in midlife. Disproportionate exposure to chronic and acute stressors during mid-life may explain Black-white differences in trajectories of cognitive function over time. In this study we use data from approximately 3,700 Black and white respondents age 51-64 from the Health and Retirement Study to examine race differences in cognitive decline and the role mid-life stress exposure play in these differences. Initial findings suggest that mid-life Blacks have lower levels of cognitive function, but their rates of cognitive decline do not differ significantly from mid-life whites. Financial strain and everyday experiences of discrimination are inversely associated with cognitive decline and only partially explain differences in cognitive decline between mid-life Blacks and whites.

African-American Race Predicts 1-Year Cognitive Decline Among Adults Without Moderate Dementia

Previous literature shows conflicting conclusions about the association between race and cognitive decline, particularly in early impairment. In this study, we aimed to test whether race predicted 1-year change in Montreal Cognitive Assessment (MoCA) score among older adults without moderate-severe dementia. We secondarily explored whether multimorbidity, polypharmacy, depressed mood, antidepressant use, body composition, or frailty changed the association. We analyzed data (n=122) from predominantly African American (AfA, 78.7%) community-dwelling older adults from the south side of Chicago. Participants underwent baseline and 1-year MoCA testing. Age, gender, race, education, monthly income, co-morbidities (Charlson Comorbidity Index), medication use (<5 vs ≥5), depression (PHQ-2), proportion lean mass (DEXA), and the frailty phenotype (range 0-5) were collected at baseline. In a multivariate linear model, we regressed 1-year MoCA score on baseline MoCA score, race, and demographics and then evaluated the impact of each covariate added separately to the model on the race-cognition relationship. The mean MoCA score at baseline was 25.2+/-0.2 (range 18-30) and 41.0% of participants experienced ≥1 point MoCA decline at 1 year. After adjusting for demographics, AfAs experienced a greater 1-year MoCA decline (β= -1.3, p=0.04) compared to other races. The effect size was unchanged after adjusting for multimorbidity and polypharmacy (β= -1.3, p=0.04), attenuated slightly after adjusting for frailty (β= -1.2, p=0.06), depressed mood (β= -1.2, p=0.05), lean mass (β= -1.2, p=0.04), and attenuated notably after adjusting for antidepressant use (β= -1.0, p=0.11). Findings support the need to further explore racial differences in cognitive decline and potentially related anti-depressant underuse.

A nuanced portrait of how race/ethnicity and nativity influence cognitive trajectories among older adults in the United States

AbstractBackgroundCognitive decline and Alzheimer Disease and Related Dementias (ADRDs) represent significant public health challenges that affect the quality of life and independence of older adults. Previous research documents large racial/ethnic disparities in cognition; However, less is known about variation in cognitive functioning trajectories within minority populations, specifically among older Latinos. Understanding how demographic and socioeconomic factors influence cognitive health in later life is particularly important given the rapidly growing and diversifying United States population.MethodWe use 18‐years of biennial Health and Retirement Study data (1998‐2016) to estimate Generalized Estimating Equations (GEE) modeling sex specific age graded changes in global cognition and memory (based on Modified Telephone Interview for Cognitive Status) among White, Black, and U.S.‐ and foreign‐born Latino adults aged 51 years and older.ResultAdjusting for socioeconomic factors, health behaviors, and chronic health conditions, we find consistent evidence for curvilinear (quadratic) associations between age and cognitive change across race/ethnic and nativity groups (bage=028; SE=0.010; p&lt;0.01 and bage2=‐0.005; SE&lt;0.0001; pp&lt;0.0001), regardless of sex. Among males, racial/ethnic and nativity differences in cognitive function were mainly evident at younger ages, particularly for Blacks compared to Whites (see Figure below). We found no evidence to support male racial/ethnic or nativity differentials in trajectories of cognitive aging. For women, older Black and US‐Born Latina adults, and to a lesser degree foreign‐born Latinas, had lower cognitive function at younger ages (see Figure). Moreover, White women showed more pronounced cognitive aging in comparison to U.S.‐ and foreign‐born Latinas (see Figure). These results were consistent for both global and memory specific outcomes.ConclusionOur findings support current calls for more nuanced considerations of racial/ethnic and nativity effects on cognitive aging and ADRDs. Understanding minority and immigrant differences in cognitive decline has implications for assessing the burden of cognitive disease and the development and implementation of culturally‐appropriate programs to promote healthy brain aging.