Greater Risk Of Cognitive Decline Research Articles

COVID-19 and Cognitive Decline in Older Adults with High-Cardiovascular Risk: A Post Hoc Analysis.

Cognitive decline has been reported as a short-term sequela in patients hospitalized for coronavirus disease-19 (COVID-19). Whether COVID-19 is associated with late cognitive impairment in older free-living individuals with high cardiovascular risk, a group at greater risk of cognitive decline, is unknown. We determined this association of COVID-19 through a longitudinal evaluation of post-COVID-19 cognitive performance and impairment as post hoc analysis in 5,179 older adults (48% female) with mean (SD) age 68.5 (5.0) years, body mass index 31.7 (3.7) kg/m2, harboring ≥ 3 criteria for metabolic syndrome (e.g., hypertension, hyperlipidemia, hyperglycemia etc.) enrolled in PREDIMED-Plus trial. Pre- and post-COVID-19 cognitive performance was ascertained from scheduled assessments conducted using a battery of neuropsychological tests, including 5 domains: Global Cognitive Function, General Cognitive Function, Execution Function, Verbal Fluency and Attention domains, which were standardized for the cohort. Cognitive impairment was defined as the bottom 10 percentile of the sample. Multivariable linear and logistic regression models assessed the association of COVID-19 with cognitive decline and impairment, respectively. After a mean 50-week follow-up, no significant associations were observed between COVID-19 status and post-COVID-19 scores of all tapped neuropsychological domains, except Global Cognitive Function (GCF). When fully adjusted, COVID-19 was marginally associated with higher (better) post-pandemic GCF score (βadj (95% CI): 0.06 (0.00, 0.13) p=.05). However, the odds for post-COVID-19 cognitive impairment in GCF domain were not associated with the disease (ORadj (95% CI): 0.90 (0.53, 1.51) p=.68). In the PREDIMED-Plus cohort, COVID-19 status and cognitive impairment determined 50 weeks post-infection showed no association in older adults at high cardiovascular risk. This suggests that cognitive changes observed shortly after COVID-19 revert over time. However, cautious interpretation is warranted as these data were obtained within the framework of a clinical trial encouraging a healthy lifestyle.

Clinical and diagnostic implications of Alzheimer's disease copathology in Lewy body disease.

Concomitant Alzheimer's disease (AD) pathology is a frequent event in the context of Lewy body disease (LBD), occurring in approximately half of all cases. Evidence shows that LBD patients with AD copathology show an accelerated disease course, a greater risk of cognitive decline and an overall poorer prognosis. However, LBD-AD cases may show heterogeneous motor and non-motor phenotypes with higher risk of dementia, and, consequently, be not rarely misdiagnosed. In this review, we summarize the state-of-the-art on LBD-AD by discussing the synergistic effects between AD neuropathological changes and Lewy pathology and their clinical relevance. Furthermore, we provide an extensive overview of neuroimaging and fluid biomarkers under assessment in LBD-AD and their possible diagnostic and prognostic value. AD pathology can be suspected in vivo by means of CSF, MRI and PET markers, whereas α-synuclein seed amplification assays (SAAs) represent to date the most promising technique to identify Lewy pathology in different biological tissues. Pathological imaging and CSF AD biomarkers are associated with a higher likelihood of cognitive decline in LBD but do not always mirror the neuropathological severity like in pure AD. The implementation of blood-based biomarkers of AD might allow the fast screening of LBD patients for AD copathology, thus improving the overall diagnostic sensitivity for LBD-AD. Finally, we discuss the literature on novel candidate biomarkers being exploited in LBD-AD to investigate other aspects of neurodegeneration, such as neuroaxonal injury, glial activation and synaptic dysfunction. The thorough characterization of AD copathology in LBD should be taken into account for the differential diagnosis of dementia syndromes, for the prognostic evaluation on an individual level and for guiding symptomatic and disease-modifying therapies.

Childhood and life‐course socioeconomic position and cognitive function in adult population of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL)

AbstractBackgroundThe Hispanic/Latino population experiences extensive socioeconomic adversity across the lifespan and is at greater risk of cognitive decline. Yet little is known about the role of life‐course socioeconomic position (SEP) and cognitive function in this population. We assessed the association between childhood SEP and cognitive function in Hispanic/Latino adults, whether this association is mediated by midlife SEP, and whether socioeconomic mobility is associated with cognitive function.MethodWe used baseline data (2008‐2011) from 9556 adults aged 45‐74 years of the Hispanic Community Health Study/Study of Latino (HCHS/SOL), a multi‐center cohort study conducted in four major U.S cities. We determined childhood SEP using parental educational attainment. Midlife SEP was determined through an index combining participants’ education and household income. We classified participants into socioeconomic mobility categories from childhood to adulthood (e.g., persisting low, upward mobility). Cognitive function was ascertained using neurocognitive tests, including the Six‐Item Screener; Brief‐Spanish English Verbal Learning Test Sum and Recall, Controlled Oral Word Association (or Word Frequency), and the Digit Symbol Substitution Test. Using confirmatory factor analysis and these tests we created a global cognition score. We also standardized z‐score of these neurocognitive measures. Survey linear regression models were performed adjusting for age, sex, Hispanic background, U.S born, smoking, depression, and cardiovascular factors. We also conducted mediation analysis to decompose the direct effect of childhood SEP on cognition and the indirect effect through midlife SEP.ResultChildhood SEP showed a graded association with cognitive function in adulthood with a dose‐response relationship across levels of parental education (β and [95% Confidence Interval (CI)]): Elementary/middle school vs. No schooling 0.34 [0.25‐0.43]; High school (HS) vs. No schooling: 0.53 [0.42‐0.64]; and >HS vs. No schooling: 0.68 [0.57‐0.79]). High midlife SEP was also associated with greater cognitive function relative to low midlife SEP. 37% (95% CI 32%‐44%) of the association between childhood SEP and cognition was mediated through midlife SEP. Holding a high SEP over the life‐course was associated with greater cognitive performance (β: 0.90, 95% CI: 0.79‐1.00) as compared with a persisting low SEP.ConclusionThis study provides evidence that childhood and life‐course SEP influence cognitive performance in adulthood

6 Depressive Symptoms are Associated With Decline Over Time in Verbal Fluency Performance in Female but not Male Community-Dwelling Older Adults

Objective:Late-life depression is prevalent among older adults and the presence of depressive symptoms has been shown to be associated cross-sectionally with worse verbal fluency performance. There is limited and mixed evidence as to whether depressive symptoms impact change in verbal fluency performance over time, and whether gender impacts this relationship.Participants and Methods:Participants were community-dwelling older adults who were dementia-free at baseline (N = 522; M age = 75.96, SD + 6.46 years). Baseline depressive symptoms were measured using the Geriatric Depression Scale. Category fluency and letter fluency performance, using the Controlled Oral Word Association Test (COWAT), were examined annually. Linear mixed effects models stratified by gender examined whether associations between baseline depressive symptoms and changes in fluency performance over five years were different in female (n = 289) as compared to male (n = 233) participants. Sensitivity analyses excluding participants with prevalent or incident mild cognitive impairment (MCI) (n = 141), excluding participants with incident dementia (n = 28), and excluding participants with prevalent or incident MCI or incident dementia (n = 169) were run. All analyses were adjusted for age, years of education, estimated premorbid functioning, and health comorbidities.Results:Depression was minimal across participants (m = 4.72, SD + 3.96). A subset of participants (n = 44) reported “possible depression,” namely levels suggestive of subclinical depression, according to clinical cutoffs. The “possible depression” group included 31 females (10.73% of females) and 13 males (5.58% of males), and the “no depression” group included 258 females (89.27% of females) and 220 males (94.42% of males). Baseline levels of depressive symptoms suggestive of subclinical depression were associated with worse decline in category fluency performance during longitudinal follow-up in females (estimate = -0.16, p = .002) but not males (estimate = -0.03, p = .658). Results remained the same when excluding prevalent and incident MCI cases (estimate = -0.19, p = .005), excluding incident dementia cases (estimate = -0.12, p = .017), and excluding prevalent and incident MCI and incident dementia cases (estimate = -0.20, p = .004). Letter fluency performance did not decline over time and was not influenced by levels of depressive symptoms in females (estimate = -0.03, p = .502) or males (estimate = 0.05, p = .452).Conclusions:Baseline presence of depressive symptoms suggestive of subclinical depression was associated with worse decline in category fluency performance during longitudinal follow-up in female but not male participants. Letter fluency performance did not decline and was not impacted by levels of depressive symptoms. Results remained significant when accounting for covariates and potential confounders. The present study elucidated the combined influence of gender and depressive symptoms on change in fluency performance in older adults and can aid in identifying individuals who may be at a greater risk of cognitive decline.

23 Cognitive Reserve Moderates Cognitive Functioning in Late-Life Depression

Objective:The concept of cognitive reserve (CR) explains why individuals with higher education, intelligence, or occupational attainment exhibit less severe cognitive changes in the presence of age-related or neurodegenerative pathology. CR may be a useful construct in understanding the cognitive performance of patients with late life depression (LLD), a cohort who are twice as likely to later receive a clinical diagnosis of dementia. It follows that depressed older adults with low CR may be at greater risk of cognitive decline compared to non-depressed older adults matched for CR. However, the literature on CR and LLD is limited to cross-sectional studies with mixed findings as to whether proxies of CR moderate cognitive outcomes in LLD. For example, both higher and lower education levels in LLD are associated with greater cognitive impairment in LLD compared to similarly educated non-depressed older adults. Longitudinal studies may help disentangle the association between CR and cognitive outcomes in LLD. The current study investigated the interaction between proxies of CR (e.g., education) and depression status on cognitive functioning over three years. We hypothesized that depressed older adults with low CR would demonstrate greater cognitive impairment and decline compared to depressed elders with high CR and non-depressed older adults with comparable CR.Participants and Methods:Older adults with LLD and non-depressed older adults age 59+ participated. All participants were free of dementia at baseline. We divided both patients and non-depressed participants into low (<16) and high (>=16) education groups based upon the median years of education (16) of the entire sample. All participants underwent detailed neuropsychological testing. Composite measures of episodic memory (CERAD Wordlist and recall, LM I and LM II, BVRT), processing speed-executive functioning (SDMT and Trail Making Part B), working memory (forward, reverse, ascending Digit Span), and verbal fluency (Animal Naming and COWA) were calculated based on the non-depressed older adults.Results:The baseline sample included 210 non-depressed older adults and 465 older adults with major depression (LLD). 150 non-depressed older adults and 235 LLD patients provided three-year follow-up data. Separate ANOVAs revealed a statistically significant interaction between education and depression status at baseline on the composite score of executive functioning F (1, 668) = 8.74, p <.003. Consistent with our hypothesis, LLD with low education performed significantly worse compared to non-depressed with low education (z-score difference -1.35) and this effect was significantly greater than the difference between LLD patients and non-depressed with high education (z-score difference -0.36). No other interactions were found at baseline. Longitudinal analyses also revealed significant interactions between education and depression on memory over time, although sensitivity analyses did not suggest findings consistent with our hypothesis.Conclusions:Cognitive reserve contribute to group differences between LLD and non-depressed older adults in cognitive performance but may not alter cognitive trajectories over time. Future studies should further explore structural and functional brain changes associated with CR in LLD.

Circadian rest-activity rhythms and cognitive decline and impairment in older Chinese adults: A multicohort study with prospective follow-up

BackgroundThe associations between rest-activity rhythms and cognitive health are inconclusive. The potential changes in rest-activity rhythms in older people with mild cognitive impairment (MCI) remains unclear. This study aimed to examine the association between rest-activity rhythms and cognitive health across different outcome measures in older Chinese people. MethodsA total of 710 community-dwelling participants (average age 81.1 ± 5.2 years) from two cohort studies. Wrist-worn accelerometer data was used to estimate the circadian rest-activity rhythms at baseline. Cognitive function was assessed and clinical diagnosis was made at baseline and follow-up. The two-way Analysis of Co-variance was used to compare the differences in rest-activity rhythms across participants with cognitively normal, MCI and Alzheimer's disease (AD). Logistic regression models were used to investigate the association between rest-activity rhythms and incidence of cognitive decline and impairment in a 4-year prospective follow-up of cognitively normal individuals. ResultsThere was a progressive trend of lower relative amplitude and higher activity level during the least active 5 h across participants with cognitively normal, MCI and Alzheimer's disease (AD). Among the cognitively normal participants, lower relative amplitude at baseline was associated with a greater risk of cognitive decline (per 1 SD decrease, odds ratio 1.66 [95 %CI 1.13–2.45]) and increased incidence of MCI or AD (per 1 SD decrease, 1.68 [1.12–2.50]). ConclusionsLower relative amplitude could potentially serve as a robust biomarker of cognitive decline and impairment. Further studies could evaluate the potential benefits of interventions associated with rest-activity relative amplitude to prevent or delay the progression of AD.

Quantitative sleep electroencephalogram and cognitive performance in Parkinson's disease with and without rapid eye movement sleep behavior disorder.

Parkinson's disease (PD) patients with REM sleep behavior disorder (RBD) are at greater risk for cognitive decline and RBD has been associated with alterations in sleep-related EEG oscillations. This study evaluates differences in sleep quantitative EEG (qEEG) and cognition in PD participants with (PD-RBD) and without RBD (PD-no-RBD). In this cross-sectional study, polysomnography (PSG)-derived qEEG and a comprehensive level II neuropsychological assessment were compared between PD-RBD (n = 21) and PD-no-RBD (n = 31). Following artifact rejection, qEEG analysis was performed in the frontal and central leads. Measures included Scalp-slow wave (SW) density, spindle density, morphological properties of SW and sleep spindles, SW-spindle phase-amplitude coupling, and spectral power analysis in NREM and REM. The neurocognitive battery had at least two tests per domain, covering five cognitive domains as recommended by the Movement Disorders Society Task Force for PD-MCI diagnosis. Differences in qEEG features and cognitive performance were compared between the two groups. Stepwise linear regression was performed to evaluate predictors of cognitive performance. Multiple comparisons were corrected using the Benjamini-Hochberg method. Spindle density and SW-spindle co-occurrence percent were lower in participants with PD-RBD compared to PD-no-RBD. The PD-RBD group also demonstrated higher theta spectral power during REM. Sleep spindles and years of education, but not RBD, were predictors of cognitive performance. PD participants with RBD have alterations in sleep-related qEEG compared to PD participants without RBD. Although PD-RBD participants had worse cognitive performance compared to PD-no-RBD, regression models suggest that lower sleep spindle density, rather than presence of RBD, predicts worse comprehensive cognitive score. Future studies should include longitudinal evaluation to determine whether sleep-related qEEG alterations are associated with more rapid cognitive decline in PD-RBD.

Exploring the relationship between perceived loneliness and subjective cognitive decline in older individuals

Objective Loneliness has been associated to a greater risk of cognitive decline and dementia in older individuals. However, evidence on whether this association also exists for older individuals who complain of cognitive problems is limited. We conducted a survey to examine the association between subjective cognitive decline in the working memory domain, perceived loneliness, depression, anxiety, and stress in older individuals with different profiles. Methods A total of 302 healthy, old individuals completed 3 questionnaires to assess subjective cognitive problems in attention, executive functions, storage, depression, anxiety, stress, and perceived loneliness. Results We conducted a cluster analysis and 3 clusters of individuals with different profiles emerged. Individuals with greater subjective cognitive problems (cluster 1) in the attention and storage domains, reported higher perceived loneliness and stress but not depression. In contrast, individuals with the least subjective cognitive problems (cluster 3) in the storage domain, reported lower perceived loneliness. Conclusions Individuals with higher subjective cognitive decline also report higher levels of perceived loneliness but not more depression than their peers. However, this correlation is present only for individuals with mild subjective cognitive decline (cluster 2). The implications for future research and interventions are discussed.

Depression interacts with allostatic load to predict cognitive decline in middle-age

Allostatic load (AL) indicates the cumulative impact of stress on homeostatic mechanisms. Depression and AL have been associated with cognitive deficits, but it is unclear if they do so independently. Using data from middle-aged participants in the observational longitudinal Midlife in the United States (MIDUS) study (n=708, 57.5% female, 63.8±10.6 years old in 2014), we assessed whether the effect of prior depression (Composite International Diagnostic Interview Short-Form in 1995) on cognitive decline between 2004 and 2013 (composite Z-scores derived from the Brief Test of Adult Cognition by Telephone and the Stop & Go Switch Task) was moderated by AL Z-scores in 2004 (calculated from biomarkers in blood, urine, and electrocardiography). A significant depression × AL interaction predicted a decline in a composite cognitive score (β=-0.066, SE=0.029, p=0.024) and executive function (β=-0.068, SE=0.025, p=0.007). Depression predicted a decline in composite cognition among those with AL Z-scores above -0.055. AL subdomains of lipid metabolism, glucose metabolism, cardiovascular function, and inflammation showed evidence of moderation. Middle-aged adults with depression who had higher allostatic load were at greater risk of cognitive decline. Future studies should evaluate whether the interaction predicts dementia and whether midlife interventions targeting depression and AL attenuate cognitive decline.

Longitudinal Associations Between Sleep and Cognitive Function in a Cohort of Older Puerto Rican Adults: Sex and Age Interactions.

Evidence on sleep duration or quality and cognitive function in diverse older adults is limited. We examined prospective associations between subjective sleep measures and cognitive function, with modifying effects of sex and age (<65 vs ≥65 years). Data are from the longitudinal Boston Puerto Rican Health Study, Waves 2 (n = 943) and 4 (n = 444), with mean follow-up of 10.5 years (range 7.2-12.8). Subjective measures of sleep duration (short <7, ref. 7, or long ≥8 hours) and insomnia symptoms (sum of difficulty falling asleep, waking up at night, and early morning awakening), were assessed at Wave 2. Linear regression models were used to assess changes in global cognition, executive function, memory, and Mini-Mental State Examination, and tested for modifying roles of sex and age. Significant 3-way interaction (sex × age × cognition) in fully adjusted models showed greater decline in global cognitive function in older men with short (β [95% confidence interval]: -0.67 [-1.24, -0.10]) or long sleep duration (-0.92 [-1.55, -0.30]), compared to women, younger men, and older men with 7 hours of sleep. Insomnia symptoms were associated with a greater decline in memory (-0.54, [-0.85, -0.22]) among older men, compared to women and younger men. Sleep duration showed a U-shaped association with cognitive decline, and insomnia symptoms were associated with memory decline in fully adjusted models. Older men, versus women and younger men, were at relatively greater risk for cognitive decline associated with sleep factors. These findings are important for personalizing sleep interventions to support cognitive health.

Using remote evaluations to cognitively test African American communities reduces racial disparities and enhances Alzheimer’s disease awareness

AbstractBackgroundAfrican Americans are at greater risk for cognitive decline and development of Alzheimer’s Disease than any other ethnic population. Systemic and financial barriers block access to healthcare in many African American communities, preventing possibility for evaluation and treatment. During the COVID pandemic, Neurobehavioral Systems, Inc (NBS) augmented the California Cognitive Assessment Battery to become a take‐home and remote administered platform that ensured a convenient and safe cognitive evaluation. Preliminary analysis assessed the usability of the tablets among healthy African American adults.MethodTwelve out of the 20 participants recruited from East Oakland, California, took part in this study. The average participant age was 52.58 (SD = 15.22), ranging from 22 to 69 years old, 58.3% were female. About 33.3% of the participants obtained a higher education after high school, the level of education ranging from high school diploma to graduate degree. Symptoms of dementia were not reported.Participants were repeat tested two times between March and April 2021. Testing kits contained a Microsoft Pro tablet, charger, headset, mouse, modem, and USB port, provided by NBS. Units were set up and taken down in participants’ homes by an NBS staff before and after each cognitive evaluation, respectively. The tablet’s software, California Cognitive Assessment Battery, or CCAB, was created by NBS to maintain communication between a remote evaluator and the test‐taker throughout testing.ResultTwelve African Americans adults, 58.3% women and 33.3% holding a degree higher than a high school diploma, were evaluated consecutively for two days from March through April 2021. In general, the 30‐test battery could be completed within 2 hours. Of those participating, 100% completed all 30 tests within the allotted time.ConclusionDuring a verbal exit interview with their examiner, participants preferred the remote evaluation for its comfortability and convenience, and the test helped show their cognitive ability and areas that needed work. These results demonstrated that remotely monitored cognitive evaluations administered at home have great promise in reducing healthcare disparities between African Americans and other ethnicities.

Depressive Symptoms are Associated with Decline Over Time in Verbal Fluency Performance in Female but Not Male Community-Dwelling Older Adults

ABSTRACT Objective The current study was designed to examine associations between depressive symptoms and longitudinal declines in category and letter fluency performance in a gender-stratified sample of older adults. Method Participants were community-residing older adults (females: n = 289; males: n = 233) followed annually (2011–2018) as part of a cohort study conducted at Albert Einstein College of Medicine in New York. Depressive symptoms were assessed using the Geriatric Depression Scale (GDS). Standard forms assessed category and letter fluency performance. Participants were dementia-free during study enrollment. Results The presence of baseline depressive symptoms suggestive of subclinical depression was associated with a worse longitudinal decline in category fluency performance in female but not male participants. These associations remained significant when excluding participants with prevalent and incident mild cognitive impairment and incident dementia. Irrespective of gender, letter fluency performance did not decline over time and was not influenced by the presence of depressive symptoms. Discussion The present study’s results can aid in identification of older adults who may be at greater risk for cognitive decline, and add to the limited literature examining the influence of gender on longitudinal associations between depressive symptoms and verbal fluency performance.

Association of Hypertensive Disorders of Pregnancy With Cognition in Later Life.

Studies of hypertensive disorders of pregnancy (HDP), including gestational or chronic hypertension (GH/CH) and preeclampsia/eclampsia (PE/E), suggest associations with early-life and mid-life cognition but have been limited by self-report or use of diagnostic codes, exclusion of nulliparous women, and lack of measurement of cognition in later life. We examined the effects of any HDP, GH/CH, PE/E, and nulliparity on cognition in later life. Participants included 2,239 women (median age 73) enrolled in the Mayo Clinic Study of Aging with medical record-abstracted pregnancy information. A cognitive battery of 9 tests was conducted every 15 months. Global cognitive and domain-specific z scores (memory, executive/attention, visuospatial, and language) were outcomes. Linear mixed-effect models evaluated associations between pregnancy history (all normotensive, any HPD, HPD subtype [GH/CH, PE/E], or nulliparous) and cognitive decline, adjusting for age and education. Additional models adjusted for APOE, smoking, hypertension, dyslipidemia, body mass index (BMI), diabetes, stroke, and heart disease. Interactions between pregnancy history and age or education on cognitive performance were examined. Of the 2,239 women, 1,854 (82.8%) had at least 1 pregnancy (1,607 all normotensive, 100 GH/CH, and 147 PE/E); 385 (17.2%) were nulliparous. Cognitive performance did not cross-sectionally differ for women with a history of any HDP, GH/CH, or PE/E vs women with a history of all normotensive pregnancies; women who were nulliparous had lower global and domain-specific cognition (all p < 0.05) in age- and education-adjusted models. There was an interaction (p = 0.015) between nulliparity and education such that the lower cognitive performance was most pronounced among nulliparous women with ≤12 years of education (beta = -0.42, p < 0.001) vs 12 + years (b = -0.11, p = 0.049). Longitudinally, women with any HDP had greater declines in global cognition and attention/executive z scores compared with women with all normotensive pregnancies. When stratified by HDP type, only women with PE/E had greater declines in global cognition (beta = -0.04, p < 0.001), language (beta = -0.03, p = 0.001), and attention (beta = -0.04, p < 0.001) z scores. Adjustment for vascular risk factors, BMI, smoking, and APOE did not attenuate results. Women with a history of HDP, especially PE/E, are at greater risk of cognitive decline in later life.

Association between sarcopenia and cognitive function in older Chinese adults: Evidence from the China health and retirement longitudinal study.

Sarcopenia and cognitive impairment are the most common causes of disability in the aging population. The potential role of sarcopenia in the development of cognitive impairment remains poorly understood. A cross-sectional analysis was performed using nationally representative data to evaluate associations between sarcopenia and cognition in China. We included 2,391 participants (35.63% female) who were at least 60 years of age in 2015 from the China Health and Retirement Longitudinal Study (CHARLS). Muscle strength, appendicular skeletal mass (ASM), and physical performance measurements, were measured to diagnose sarcopenia according to the Asian Working Group for Sarcopenia 2019 (AWGS2019). Cognitive function was assessed by 10 items in the Telephone Interview for Cognitive Status (TICS-10), delayed word recall, and graph drawing. Based on cognitive score tertiles, data were divided into three groups. Multiple linear and logistic regression models were used to assess the relationship between sarcopenia and cognition. The prevalence of possible sarcopenia was 27.16% for men and 27.46% for women. Cognitive decline was significantly associated with sarcopenia status (β = -0.88, p < 0.001) and negatively associated with components of sarcopenia in male group. The results remained consistent in male after further adjusting for creatinine, uric acid, blood sugar, etc. Low cognitive function in female was only associated with low muscle strength (β = -0.85, p = 0.02). In addition, participants with possible sarcopenia had greater risk of cognitive decline than those without sarcopenia (OR = 1.41; 95% CI: 1.06-1.87). However, the same association was not significant in female group. We suggest that sarcopenia might be associated with cognition function, with possible sarcopenia being significantly associated with higher cognition risk in China population, which providing a further rationale for timely recognition and management of sarcopenia.

Brain connectivity in frailty: Insights from The Irish Longitudinal Study on Ageing (TILDA)

Frailty in older adults is associated with greater risk of cognitive decline. Brain connectivity insights could help understand the association, but studies are lacking. We applied connectome-based predictive modeling to a 32-item self-reported Frailty Index (FI) using resting state functional MRI data from The Irish Longitudinal Study on Ageing. A total of 347 participants were included (48.9% male, mean age 68.2 years). From connectome-based predictive modeling, we obtained 204 edges that positively correlated with the FI and composed the “frailty network” characterised by connectivity of the visual network (right); and 188 edges that negatively correlated with the FI and formed the “robustness network” characterized by connectivity in the basal ganglia. Both networks’ highest degree node was the caudate but with different patterns: from caudate to visual network in the frailty network; and to default mode network in the robustness network. The FI was correlated with walking speed but not with metrics of global cognition, reinforcing the matching between the FI and the brain connectivity pattern found (main predicted connectivity in basal ganglia).

Associations Between Korean Coronary Heart Disease Risk Score and Cognitive Function in Dementia-Free Korean Older Adults.

Cardiovascular risk is a modifiable factor that can help prevent dementia. Given the dearth of optimal treatment options, managing dementia risk factors is crucial. We examined the association between cardiovascular risk, as measured by the Korean coronary heart disease risk score (KRS), and cognitive function in dementia-free elderly individuals. We enrolled 8,600 individuals (average age: 69.74 years; 5,206 women) who underwent a medical evaluation from the National Health Insurance Service. KRS was calculated using age, sex, blood pressure, lipid profile, diabetes, and smoking status. Cognitive function was evaluated using Korean Dementia Screening Questionnaire-Cognition (KDSQ-C). Scores of ≥ 6 indicated a cognitive decline. Logistic regression analysis was used to estimate the odds ratio (OR) and 95% confidence interval (CI). Weight, height, stroke history, coronary heart disease history, alcohol consumption, and physical activity engagement were adjusted. The lowest, middle, and highest groups, according to the KRS, were 5,923 (68.9%), 2,343 (27.2%), and 334 (3.9%), respectively. The highest KRS group in all participants exhibited a greater risk of cognitive decline than the lowest KRS group (OR, 1.339; 95% CI, 1.034-1.734; P = 0.027). The highest KRS female group aged 71-75 years old exhibited greater cognitive decline than the corresponding lowest KRS group (OR, 1.595; 95% CI, 1.045-2.434; P = 0.031). Individuals with high cardiovascular risk were associated with poorer cognitive function than those with low risk, especially older women. Cardiovascular risk factors should be carefully managed to promote healthy mental aging in dementia-free elderly individuals.

Synergistic associations of depressive symptoms and aging on cognitive decline in early Parkinson’s disease

ObjectiveParkinson's disease (PD) is the second most common progressive neurodegenerative disorder. About 40%–50% of PD patients experience depression, making it one of the most common neuropsychiatric disturbances in PD. Cognitive deficits (e.g., difficulties with memory, attention) are an additional common complication in PD. Past studies among healthy aging individuals suggest that depression is a risk factor for cognitive decline, and the risk increases with older age. This study aims to examine the association between depressive symptoms on cognitive decline as a function of age among patients with PD. It is hypothesized that older PD patients with more severe depressive symptoms will be at greater risk of cognitive decline than their younger or less depressed counterparts. MethodsFour hundred and eighty-seven newly diagnosed patients with PD, were assessed for depression and cognition over a five-year period. Participants completed neuropsychological tests that assessed memory, learning, attention, visuospatial functioning, processing speed, and verbal fluency. Multilevel-modeling was used to examine the longitudinal association between cognition, age, and depressive symptoms. ResultsOur results indicated a significant three-way interaction (age X occasion X depressive symptoms) predicting language and working memory/attention performance. More specifically, detrimental associations of depressive symptoms on cognitive decline in these domains were more pronounced among older adults. ConclusionsOur findings support that older PD patients with comorbid depressive symptoms experience greater cognitive decline compared to their younger counterparts. Findings suggest that older individuals with PD may be more vulnerable to neurotoxic effects of depression (e.g., neuroinflammation, HPA axis disruption), and better management of depression could potentially reduce cognitive decline and dementia risk.

Sensorimotor and Frontoparietal Network Connectivity Are Associated With Subsequent Maintenance of Gait Speed and Episodic Memory in Older Adults.

Slow gait is predictive of functional impairments in older adults, while concomitant slow gait and cognitive complaints are associated with a greater risk for cognitive decline and dementia. However, functional neural correlates for gait speed maintenance are unclear. As the sensorimotor network (SMN) and frontoparietal network (FPN) are integral components of these functions, this study investigated differences in SMN and FPN in older adults with/without gait speed decline over 24 months; and whether these networks were associated with the maintenance of cognitive function. We included 42 community-dwelling older adults aged >70 years from the MOBILIZE Boston Study. Resting-state fMRI was performed at the study baseline. Participant characteristics, gait speed, Mini-Mental State Examination, and Hopkins Verbal Learning Test (HVLT) were assessed at baseline and at 24-month follow-up. Decliners were identified as individuals with >0.05 meters/second decline in gait speed from baseline to 24 months. Of the 26 decliners and 16 maintainers, decliners exhibited a significant decline in delayed-recall performance on the HVLT over 24 months. Controlling for baseline age and multiple comparisons, contrary to initial hypothesis, maintainers exhibited lower baseline primary motor and premotor connectivity (p = .01) within the SMN, and greater baseline ventral visual-supramarginal gyrus connectivity within the FPN (p = .02) compared to decliners. Lower primary motor-premotor connectivity was correlated with maintenance of delayed-recall performance on the HVLT (p = .04). These findings demonstrated a potential compensatory mechanism involved in the link between the decline in gait speed and episodic memory, whereby baseline connectivity of the SMN and FPN may underlie subsequent maintenance of gait speed and cognitive function in old age.

Depression interacts with allostatic load to predict cognitive decline in middle age

BackgroundAllostatic load (AL) indicates the cumulative impact of stress on homeostatic mechanisms. Depression and AL have been associated with cognitive deficits, but it is unclear if they do so independently. MethodsUsing data from middle-aged participants in the observational longitudinal Midlife in the United States (MIDUS) study (n = 704, 57.5 % female, 63.8 ± 10.6 years old in 2014), we assessed whether the effect of prior depression (Composite International Diagnostic Interview Short-Form in 1995) on cognitive decline between 2004 and 2013 (composite Z-scores derived from the Brief Test of Adult Cognition by Telephone and the Stop & Go Switch Task) was moderated by AL Z-scores in 2004 (calculated from biomarkers in blood, urine, and electrocardiography). ResultsA significant depression × AL interaction predicted a decline in a composite cognitive score (β = −0.066, SE=0.029, p = 0.024) and executive function (β = −0.068, SE=0.025, p = 0.007). Depression predicted a decline in composite cognition among those with AL Z-scores above − 0.055. AL subdomains of inflammation and lipid metabolism showed evidence of moderation. ConclusionMiddle-aged adults with depression who had higher allostatic load were at greater risk of cognitive decline. Future studies should evaluate whether the interaction predicts incident dementia, and whether interventions targeting depression or elevated AL in people who have both can attenuate cognitive decline.

Contributions of sex and genotype to exploratory behavior differences in an aged humanized APOE mouse model of late-onset Alzheimer's disease.

Age, genetics, and chromosomal sex have been identified as critical risk factors for late-onset Alzheimer's disease (LOAD). The predominant genetic risk factor for LOAD is the apolipoprotein E ε4 allele (APOE4), and the prevalence of LOAD is higher in females. However, the translational validity of APOE4 mouse models for AD-related cognitive impairment remains to be fully determined. The present study investigated the role of both sex and genotype on learning and memory in aged, humanized APOE knock-in mice. Aged (23.27 mo ± 1.21 mo; 39 male/37 female) APOE3/3, APOE3/4, and APOE4/4 mice performed a novel object recognition (NOR) assay. Task-related metrics were analyzed using two-way sex by genotype ANOVAs. Sex differences were more prominent relative to APOE genotype. Prior to NOR, female mice exhibited thigmotaxic center zone avoidance during the open field task relative to males, regardless of genotype. Within object familiarization and NOR tasks, females had greater object interaction and locomotion. Interestingly, only APOE4/4 females on average recognized the novel object. These results suggest that APOE4, although strongly related to LOAD pathogenesis, does not drive cognitive decline in the absence of other risk factors even in very aged mice. Chromosomal sex is a key driver of behavioral phenotypes and thus is a critical variable for translatability of interventions designed to preserve learning and memory in animal models of LOAD. Last, there was a very high degree of variability in behavioral performance across APOE genotypes. A cluster analysis of the behavioral data revealed a low-activity and a high-activity cluster. APOE4 carriers were overrepresented in the low-activity cluster, while male:female distributions did not differ. Collectively, the behavioral data indicate that chromosomal sex has the greatest impact on behavioral phenotype, and APOE4 carrier status may confer greater risk for cognitive decline in some animals.