Change In Global Cognition Research Articles

Effects of novel Cognitive Stimulating Activities (CSAs) on cognition and depression: A 5‐year pragmatic and naturalistic study

AbstractBackgroundAccumulating epidemiological evidence suggest that cognitive stimulating activities (CSAs) improve cognition in older adults. However, there is a lack of longitudinal naturalistic follow‐up studies supporting the effectiveness of CSAs, particularly in a real‐world setting. Whether baseline cognitive status affects cognitive outcomes, and whether a higher involvement in CSAs elicits greater improvements are unknown. We aimed to investigate a novel multimodal CSA intervention to prevent cognitive decline amongst community‐dwelling older adults.MethodFrom the Singapore Longitudinal Diet and Healthy Aging (DaHA) study (n=991, aged ≥60), 264 subjects were assigned to the novel multimodal CSAs controlled trials (mindfulness intervention, horticultural therapy, arts and music reminiscence therapy, and choral singing). The other participants not involved in the CSAs (n=727) served as the control group. At the DaHA cohort’s 5‐year follow‐up, we examined the effects of CSAs on cognitive function. The primary outcomes were changes in global cognition measured by the mini‐mental state examination (MMSE) and its domain scores. Intention‐to‐treat analysis was performed utilizing a linear mixed model. We also conducted sub‐group analyses stratified by baseline cognitive status and the number of CSAs involved.ResultCompared to the control group, although non‐significant, there was an improvement in the CSA group after five years based on the total MMSE score (β =0.108, 95% CI= ‐0.022 to 0.239, P =0.104). Notably, there was a significant improvement in MMSE‐immediate recall score domain (β = 0.199, 95% CI = 0.048 to 0.351, P = 0.010). Sub‐group analyses showed that older adults with MCI and those involved in more CSAs had greater improvements in total MMSE and selective domain scores after 5 years, with effect sizes of Cohen’s D=0.42.ConclusionAlthough global cognition was not significantly improved, the multimodal CSA intervention showed significant improvements in the scores of working memory domain, possibly, highlighting the high malleability of this cognitive domain. Furthermore, moderate effect sizes of improvements observed in the MCI sub‐group and those involved in more CSAs suggesting that these individuals could gain greater long‐term benefits participating in CSAs. From a public health perspective, these sustained improvements in cognitive functions over five years’ time could potentially delay or prevent dementia.

Links between acculturation and level and change in cognition among middle‐aged and older Hispanics/Latinos: Findings from the HCHS/SOL and SOL‐INCA

AbstractBackgroundHispanics/Latinos in the United States vary widely in their levels of acculturation (adoption of Anglo‐American culture) which may have implications for cognitive functioning in older age. We aimed to characterize the relationships of acculturation with cognition and cognitive change among diverse U.S. Hispanics/Latinos.MethodSelected Hispanics/Latinos (unweighted n=5,901; ages 50+ years) from the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) were enrolled in the Study of Latinos ‐ Investigation of Neurocognitive Aging (SOL‐INCA) ancillary study. Three measures of acculturation were collected at baseline (Short Acculturation Scale for Hispanics (SASH) – Social and Language subscales (Marin et al., 1987) and MESA Acculturation score (Kandula et al., 2008). On all measures higher scores reflect greater acculturation. Cognition was measured at two time‐points, on average, 7‐years apart. Global cognition based on a composite measure from learning and memory, executive functioning, and processing speed tests at the second testing was the main outcome of interest in addition to change in global scores. Survey linear regressions were used to separately model the associations between acculturation measures (quartiles) and cognitive outcomes (z‐scores), controlling for baseline age, sex, education, Hispanic/Latino background, field center, income, marital status, and insurance status.ResultAverage age of the target population was 63.3 ± 8.3(SD) years, 55% were female, 39% reported less than high school education, and 43% were currently uninsured. Adjusting for covariates, the least acculturated (lowest quartile) according to the SASH had lower global cognition compared to all other groups (all p‐values<0.01; Social subscale: b=0.10; SE=0.03, b=0.15; SE=0.03, and b=0.13; SE=0.03, for the 2nd, 3rd, and 4th quartiles respectively; Language subscale: b=0.15; SE=0.03, b=0.12; SE=0.03, and b=0.23; SE=0.03). Individuals with the lowest MESA acculturation quartile had lower global cognition relative to those with scores in the highest quartile only (b=0.13; SE=0.04; p<0.01). None of the acculturation indices were associated with global cognitive change. Associations with domain specific cognitive outcomes were largely similar in pattern.ConclusionAcculturation may be indicative of baseline differences in cognition rather than risk for cognitive change. Alternatively, acculturation‐based distinctions in cognition may be related to differences in familiarity with testing environments or approaches to cognitive tasks.

A randomised controlled trial of psychotherapy and cognitive remediation to target cognition in mood disorders.

To examine the impact of a treatment package combining Interpersonal and Social Rhythm Therapy (IPSRT) and cognitive remediation (CR), vs IPSRT alone, on cognition, functioning, and mood disturbance outcomes in mood disorders. A pragmatic randomised controlled trial in adults with bipolar disorder (BD) or major depressive disorder (MDD), recently discharged from mental health services in Christchurch, New Zealand, with subjective cognitive difficulties. Individuals were randomised to a 12-month course of IPSRT with CR (IPSRT-CR), or without CR (IPSRT). In IPSRT-CR, CR was incorporated into therapy sessions from approximately session 5 and continued for 12 sessions. The primary outcome was change in Global Cognition (baseline to 12months). Sixty-eight individuals (BD n=26, MDD n=42; full/partial remission n=39) were randomised to receive IPSRT-CR or IPSRT (both n=34). Across treatment arms, individuals received an average of 23 IPSRT sessions. Change in Global Cognition did not differ between arms from baseline to treatment-end (12months). Psychosocial functioning and longitudinal depression symptoms improved significantly more in the IPSRT compared with IPSRT-CR arm over 12months, and all measures of functioning and mood symptoms showed moderate effect size differences favouring IPSRT (0.41-0.60). At 18months, small to moderate, non-significant benefits (0.26-0.47) of IPSRT vs IPSRT-CR were found on functioning and mood outcomes. Combining two psychological therapies to target symptomatic and cognitive/functional recovery may reduce the effect of IPSRT, which has implications for treatment planning in clinical practice and for CR trials in mood disorders.

Change in Patients' Perceived Cognition Among Chimeric Antigen Receptor T-Cell Therapy Recipients at Day 360

Change in Patients' Perceived Cognition Among Chimeric Antigen Receptor T-Cell Therapy Recipients at Day 360

Association between intra-individual changes in social network diversity and global cognition in older adults: Does closeness to network members make a difference?

ObjectiveAlthough qualitative aspects of interpersonal networks, such as diversity or closeness, can protect the health of older adults, their association with cognitive health remains unclear. This study examined the concurrent and time-lagged association between intra-individual changes in global cognition and social network diversity, while considering emotional closeness. MethodsIn this 10-year study, we obtained six-wave, biennial data from the National Institute for Longevity Sciences, Longitudinal Study of Aging. Data from 808 community-dwelling, cognitively intact adults aged 65 or older at baseline were analyzed. Global cognition was assessed using the Mini-Mental State Examination (MMSE). Social network diversity scores were assessed using a social convoy model, comprising three closeness levels: inner (closest), middle (second closest), and outer (least close). ResultsThe mean age of the respondents was 72.0 ± 4.4 years at baseline, and 50.1% were male. A fixed-effects model showed that intra-individual change in total (coefficients, B: 0.10; standard error [SE]: 0.05; p = .042) and inner (B: 0.25; SE: 0.07; p < .001) social network diversity was significantly associated with MMSE score decline, even after adjusting for covariates. Yet, in time-lagged models, diversity and MMSE score changes were not significantly associated during the subsequent two years. ConclusionOlder adults' global cognition declined when the diversity of their closest social network decreased. This may be a promising marker for early cognitive decline in older adults. Indeed, their closest networks are relatively unlikely to decline as part of normal aging or diseases except dementia.

Interplay between cognition and weight reduction in individuals following a Mediterranean Diet: Three-year follow-up of the PREDIMED-Plus trial

Some cognitive profiles might facilitate successful weight loss and its maintenance. Also, weight reductions may result in cognitive benefits. However, little work to date has examined the interactions between cognition and weight changes in the context of interventions with the Mediterranean diet (MedDiet). We studied the within-subject longitudinal relationships between cognition, body mass index (BMI), physical activity (PA), and quality of life (QoL), in older adults following a MedDiet. The PREDIMED-Plus is a primary prevention trial testing the effect of a lifestyle intervention program with an energy-restricted MedDiet (er-MedDiet), weight-loss goals and PA promotion on cardiovascular disease. The PREDIMED-Plus-Cognition sub-study included 487 participants (50% women, mean age 65.2 ± 4.7 years), with overweight/obesity, metabolic syndrome and normal cognitive performance at baseline. A comprehensive neurocognitive test battery was administered at baseline and after 1 and 3 years. Baseline higher performance in verbal memory (OR=1.5; 95%CI 1.0, 2.1), visuoconstructive praxis and attention (OR=1.5; 95%CI 0.9, 2.3), and inhibition (OR=1.3; 95%CI 0.9, 1.9) were associated with a higher odd of achieving at least 8% weight loss after 3 years follow-up in participants randomized to the intervention group. There were moderate improvements in specific tests of memory and executive functions during follow-up. Higher adherence to the er-MedDiet was associated with greater improvements in memory. Women exhibited lower rates of change in global cognition, PA and QoL. Moreover, improvements in memory correlated with reductions in BMI after 1 year (βSTD=-0.14) and with improvements in PA after 3 years (βSTD=0.13). Finally, participants who experienced greater improvements in executive functions and global cognition also experienced greater improvements in their QoL. This study refines the understanding of the determinants and mutual interrelationships between longitudinally-assessed cognitive performance and weight loss, adding further evidence to the cognitive benefits associated with better adherence to a MedDiet. Our results also suggest that weight loss interventions tailored to the cognitive profile and gender of participants are promising avenues for future studies.

Longitudinal Cognitive Profiles by Anxiety and Depressive Symptoms in American Older Adults With Subjective Cognitive Decline.

The objective of this study was to determine how anxiety and/or depressive symptoms differentially affect specific cognitive domains over time in persons with subjective cognitive decline (SCD). A longitudinal, observational study was conducted using data from the National Alzheimer's Coordinating Center-Uniform Data Set. Mean follow-up was 4.1±2.4years. Using information from a total of 1401 participants (age 74.0±8.2years), linear mixed-effects regression models were used to assess longitudinal changes in global cognition, episodic memory, attention, language, and executive function by baseline psychological (anxiety [A] and/or depressive [D]) symptoms in individuals with SCD. Reference was the group having no symptoms (A-/D-). The A+/D- group was not associated with any cognitive changes. The A-/D+ group was associated with a greater decline in episodic memory and executive function. The A+/D+ group had a greater decline in attention. Changes in global cognition and language were not predicted by any psychological symptoms. Depressive symptoms predicted lower episodic memory and executive function. Nurses need to pay attention to depressive symptoms in older adults with SCD because managing depressive symptoms may help protect against cognitive decline more typical of early Alzheimer's dementia.

Longitudinal Associations between the Neighborhood Built Environment and Cognition in US Older Adults: The Multi-Ethnic Study of Atherosclerosis.

Few studies have examined associations between neighborhood built environments (BE) and longitudinally measured cognition. We examined whether four BE characteristics were associated with six-year change in global cognition and processing speed. We obtained data on 1816 participants without dementia from the Multi-Ethnic Study of Atherosclerosis. BE measures included social destination density, walking destination density, proportion of land dedicated to retail, and network ratio (street connectivity). Global cognition was measured with the Cognitive Abilities Screening Instrument (CASI) and processing speed with the Digit Symbol Coding test (DSC). Multivariable random intercept logistic models tested associations between neighborhood BE at 2010–2012 and maintained/improved cognition (versus decline) from 2010–2018, and mediation by minutes of physical activity (PA)/week. The sample was an average of 67 years old (standard deviation = 8.2) (first cognitive measurement) and racially/ethnically diverse (29% African American, 11% Chinese, 17% Hispanic, 44% White). Compared to individuals with no walking destinations in the 1-mile surrounding their residence, those with 716 walking destinations (maximum observed) were 1.24 times more likely to have maintain/improved DSC score (Odds ratio: 1.24; 95% confidence interval: 1.03–1.45). No other associations were observed between BE and cognition, and PA minutes/week did not mediate the association between walking destination density and DSC change. This study provides limited evidence for an association between greater neighborhood walking destinations and maintained/improved processing speed in older age and no evidence for associations between the other BE characteristics and cognition. Future studies with finer grained BE and cognitive measures and longer-term follow up may be required.

Increased reporting of subjective cognitive complaints over time predicts cognitive decline and incident dementia.

Subjective cognitive complaints (SCCs) are a risk factor for dementia; however, little is known about their trajectories. Participants were 873 older adults (mage=78.65 years; 55% females) from the Sydney Memory and Ageing Study that were followed-up biennially. SCCs were measured using the six-item Memory Complaint Questionnaire. Associations between initial level of SCC reporting, linear change in SCC reporting, and change in global cognition over 6years was examined using latent growth curve analysis. Risk of dementia was examined over 10years using Cox regression. After controlling for demographics, mood and personality, results revealed a negative longitudinal association between the slope of SCCs and the slope of global cognition scores (b=-0.01, p=0.005, β=-0.44), such that participants who reported increasing SCCs showed a steeper rate of decline in global cognition over 6years. Cox regression also revealed participants who reported increasing SCCs had a nearly fourfold increased risk of developing dementia over 10years (hazard ratio 3.70, 1.24-11.01). This study explored whether initial levels of, and change in, SCCs over time are associated with both cognitive decline and risk of dementia. These findings are clinically relevant as GPs should note patients reporting increasing SCCs as they may be at greater risk of cognitive decline and incident dementia.

Exercise, diet, and cognition in a 4-year randomized controlled trial: Dose-Responses to Exercise Training (DR’s EXTRA)

ABSTRACTBackgroundEvidence for the effects of exercise and dietary interventions on cognition from long-term randomized controlled trials (RCTs) in large general populations remains insufficient.ObjectiveThe objective of our study was to investigate the independent and combined effects of resistance and aerobic exercise and dietary interventions on cognition in a population sample of middle-aged and older individuals.MethodsWe conducted a 4-y RCT in 1401 men and women aged 57–78 y at baseline. The participants were randomly assigned to the resistance exercise, aerobic exercise, diet, combined resistance exercise and diet, combined aerobic exercise and diet, or control group. Exercise goals were at least moderate-intensity resistance exercise ≥2 times/wk and at least moderate-intensity aerobic exercise ≥5 times/wk. Dietary goals were ≥400 g/d of vegetables, fruit, and berries; ≥2 servings of fish/wk; ≥14 g fiber/1000 kcal; and ≤10% of energy of daily energy intake from SFAs. The primary outcome was the change in global cognition measured by the total score of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological tests [CERAD total score (CERAD-TS)]. The data were analyzed using the intention-to-treat principle and linear mixed-effects models.ResultsThere was a trend toward improved CERAD-TS over 4 y in the combined aerobic exercise and diet group compared with the control group (net increase: 1.4 points; 95% CI: 0.1, 2.7; P = 0.06) adjusted for age, sex, years of education, symptoms of depression, and waist circumference at baseline. No other differences in CERAD-TS changes were found across the 6 study groups. Diet did not potentiate the effect of aerobic or resistance exercise on CERAD-TS.ConclusionsA combination of at least moderate-intensity aerobic exercise and a healthy diet may improve cognition in older individuals over 4 y, but there was no effect of either of these interventions alone, resistance training alone, or resistance exercise with a healthy diet on cognition.

Abstract P149: Sedentary Behavior In Mid-life And Risk Of Change In Global Cognitive Function And Incident Dementia: The Atherosclerosis Risk In Communities Neurocognitive Study (ARIC-NCS)

Introduction: Sedentary behavior (SB) has emerged as a risk factor that may exert health effects independent from moderate-to-vigorous intensity physical activity (PA). However, the role of SB on cognitive health and its interaction with PA has not been widely examined prospectively. We tested the hypotheses that higher levels of, and persistence of mid-life television viewing, an established proxy measure of leisure-time SB, are associated with faster rates of cognitive decline and greater incidence of dementia, and that these associations are attenuated by meeting/not meeting the 2018 PA guidelines. Methods: ARIC participants (n=10,700, mean age: 59 years, 44% male, 19% Black) with self-reported assessments of television viewing at visits 1 (1987-1989) and 3 (1993-1995) were included. Participants were categorized as low [“never”/“seldom”], medium [“sometimes”], or high [“often”/“very often”] television viewing. Persistence in television viewing was quantified as the same reported television viewing at visits 1 and 3 (n=6,462). Cognitive tests of working memory, language, and executive function were administered at visits 4 (1996-1998) and 5 (2011-2013), and a factor analysis was used to derive a global cognition factor score. Dementia diagnoses were based on a battery of cognitive tests and expert adjudication. Additional cases were identified through hospital discharge codes and diagnostic codes from death certificates. Linear mixed models estimated the associations of SB categories with change in global cognition. Time to dementia was estimated using Cox proportional hazards regression models. Models were adjusted for age, education, race-ARIC field center, and APOE-ε4. Interactions with PA, categorized as meeting/not meeting PA guidelines, were tested. Results: Over a median follow-up of 17.4 years, 1,063 dementia cases were observed. In unadjusted models, high vs. low television viewing was associated with higher incident dementia (hazard ratio [95% CI], 1.42 [1.18, 1.71]); however, this association was no longer significant in multivariable adjusted models (1.09 [0.90, 1.32]). Significantly faster rates of decline in global cognition were observed for participants with high (-0.04 standard deviation (SD) difference [-0.08, -0.002]) or medium (-0.04 SD difference [-0.08, -0.004]) vs. low television viewing in multivariable adjusted models. These associations were stronger when measured as persistent mid-life television viewing (stable high vs. stable low: -0.06 SD difference [-0.11, -0.01]). The interaction of television viewing with PA guidelines on change in global cognition was statistically null. Conclusions: TV viewing, a proxy SB measure, is associated with cognitive decline, but not incident dementia. Longitudinal studies with device-based measures are needed to test the associations of accumulated daily SB on cognition and dementia outcomes.

Associations of subjective cognitive and memory decline with depression, anxiety, and two-year change in objectively-assessed global cognition and memory

ABSTRACT Research studies exploring the association of cognitive complaints with objectively assessed cognitive decline report inconsistent results. However, many of these have methodological limitations. We investigated whether 1) more severe subjective cognitive decline (SCD) and subjective memory decline (SMD) predict change in objectively assessed global cognition, remote memory, recent memory, learning; 2) the predictive value of more severe SMD over change in objectively assessed remote memory, recent memory, and learning is stronger for individuals that report an SMD that started within the past five years than for those that report an SMD that started five or more years previously and/or stronger for those that experienced SMD within the past two years than for those who had not; and 3) greater depression and anxiety are associated with more severe SCD and SMD. We used two-year longitudinal data from the CFAS-Wales study (N = 1,531; mean (SD) age = 73.0 (6.0) years). We fitted linear regression models. More severe SCD and SMD did not predict change in objectively assessed global cognition, remote memory, and recent memory but predicted lower scores in learning. The prediction of SMD over change in learning was not stronger when individuals reported an SMD that started within the past five years compared to when they reported an SMD that started five or more years previously nor when individuals reported an SMD that started within the past two years than those who did not. Greater depression and anxiety were associated with more severe SCD and SMD. More severe SMD may be useful for predicting lower learning ability and for identifying individuals experiencing depression and anxiety.

Effectiveness, Core Elements, and Moderators of Response of Cognitive Remediation for Schizophrenia

Cognitive impairment is a core feature of schizophrenia, with negative consequences on functional outcomes. Although cognitive remediation (CR) is effective and mentioned in treatment guidance for schizophrenia, its active ingredients and ideal candidates are still debated. To provide a comprehensive update on CR effectiveness for cognition and functioning in schizophrenia and analyze the core ingredients of efficacy and role of patient characteristics. The reference list of the last comprehensive meta-analysis in 2011 was screened against eligibility criteria. Then, electronic databases (PubMed, Scopus, and PsycInfo) were systematically searched for articles published from January 2011 to February 2020. Reference lists of included articles and relevant reviews were hand searched, and Google Scholar was manually inspected. Eligible studies were randomized clinical trials comparing CR with any other control condition in patients diagnosed with schizophrenia spectrum disorders (with an unrestricted clinical status). Screening was performed by at least 2 independent reviewers. The PRISMA guidelines were followed. Study data were independently extracted and pooled using random-effect models. Cohen d was used to measure outcomes. Trial methodological quality was evaluated with the Clinical Trials Assessment Measure. Primary outcomes were changes in global cognition and overall functioning from baseline to after treatment, subsequently investigated through metaregressions, subgroup, and sensitivity analyses based on prespecified hypotheses, to identify potential moderators of response associated with treatment modality and patient characteristics. Of 1815 identified reports, 358 full texts were assessed and 194 reports on 130 studies were included. Based on 130 studies with 8851 participants, CR was effective on cognition (d, 0.29 [95% CI, 0.24-0.34]) and functioning (d, 0.22 [95% CI, 0.16-0.29]). An active and trained therapist (cognition: χ21, 4.14; P = .04; functioning: χ21, 4.26; P = .04), structured development of cognitive strategies (cognition: χ21, 9.34; P = .002; functioning: χ21, 8.12; P = .004), and integration with psychosocial rehabilitation (cognition: χ21, 5.66; functioning: χ21, 12.08) were crucial ingredients of efficacy. Patients with fewer years of education (global cognition: coefficient, -0.055 [95% CI, -0.103 to -0.006]; P = .03; global functioning: coefficient, -0.061 [95% CI, -0.112 to -0.011]; P = .02), lower premorbid IQ (global functioning: coefficient, -0.013 [-0.025 to -0.001]; P = .04), and higher baseline symptom severity (global cognition: coefficient, 0.006 [95% CI, 0.002 to 0.010]; P = .005) emerged as optimal candidates. These findings show that CR is an evidence-based intervention that should be included consistently into clinical guidelines for the treatment of individuals with schizophrenia and implemented more widely in clinical practice.

Systemic brain derived neurotrophic factor but not intestinal barrier integrity is associated with cognitive decline and incident Alzheimer's disease.

The inflammatory hypothesis posits that sustained neuroinflammation is sufficient to induce neurodegeneration and the development of Alzheimer’s disease (AD) and Alzheimer’s dementia. One potential source of inflammation is the intestine which harbors pro-inflammatory microorganisms capable of promoting neuroinflammation. Systemic inflammation is robustly associated with neuroinflammation as well as low levels of brain derived neurotrophic factor (BDNF) in the systemic circulation and brain. Thus, in this pilot study, we tested the hypothesis that intestinal barrier dysfunction precedes risk of death, incident AD dementia and MCI, cognitive impairment and neuropathology. Serum BDNF was associated with changes in global cognition, working memory, and perceptual speed but not risk of death, incident AD dementia, incident MCI, or neuropathology. Neither of the markers of intestinal barrier integrity examined, including lipopolysaccharide binding protein (LBP) nor intestinal fatty acid binding protein (IFABP), were associated with risk of death, incident AD dementia, incident mild cognitive impairment (MCI), change in cognition (global or domains), or neuropathology. Taken together, the data in this pilot study suggest that intestinal barrier dysfunction does not precede diagnosis of AD or MCI, changes in cognition, or brain pathology. However, since MCI and AD are related to global cognition, the findings with BDNF and the contiguous cognitive measures suggest low power with the trichotomous cognitive status measures. Future studies with larger sample sizes are necessary to further investigate the results from this pilot study.

Sex Differences in Cognitive Decline Among US Adults

Sex differences in dementia risk are unclear, but some studies have found greater risk for women. To determine associations between sex and cognitive decline in order to better understand sex differences in dementia risk. This cohort study used pooled analysis of individual participant data from 5 cohort studies for years 1971 to 2017: Atherosclerosis Risk in Communities Study, Coronary Artery Risk Development in Young Adults Study, Cardiovascular Health Study, Framingham Offspring Study, and Northern Manhattan Study. Linear mixed-effects models were used to estimate changes in each continuous cognitive outcome over time by sex. Data analysis was completed from March 2019 to October 2020. Sex. The primary outcome was change in global cognition. Secondary outcomes were change in memory and executive function. Outcomes were standardized as t scores (mean [SD], 50 [10]); a 1-point difference represents a 0.1-SD difference in cognition. Among 34 349 participants, 26 088 who self-reported Black or White race, were free of stroke and dementia, and had covariate data at or before the first cognitive assessment were included for analysis. Median (interquartile range) follow-up was 7.9 (5.3-20.5) years. There were 11 775 (44.7%) men (median [interquartile range] age, 58 [51-66] years at first cognitive assessment; 2229 [18.9%] Black) and 14 313 women (median [interquartile range] age, 58 [51-67] years at first cognitive assessment; 3636 [25.4%] Black). Women had significantly higher baseline performance than men in global cognition (2.20 points higher; 95% CI, 2.04 to 2.35 points; P < .001), executive function (2.13 points higher; 95% CI, 1.98 to 2.29 points; P < .001), and memory (1.89 points higher; 95% CI, 1.72 to 2.06 points; P < .001). Compared with men, women had significantly faster declines in global cognition (-0.07 points/y faster; 95% CI, -0.08 to -0.05 points/y; P < .001) and executive function (-0.06 points/y faster; 95% CI, -0.07 to -0.05 points/y; P < .001). Men and women had similar declines in memory (-0.004 points/y faster; 95% CI, -0.023 to 0.014; P = .61). The results of this cohort study suggest that women may have greater cognitive reserve but faster cognitive decline than men, which could contribute to sex differences in late-life dementia.

A history of cigarette smoking is associated with faster functional decline and reduction of entorhinal cortex volume in mild cognitive impairment.

Little is known about the longitudinal association of cigarette smoking with Alzheimer’s Disease (AD) related markers in subjects with mild cognitive impairment (MCI). In this study, we aimed to examine the effect of a history of cigarette smoking on change in global cognition, verbal memory, functional performance, hippocampal volume, entorhinal cortex volume, brain glucose metabolism, and CSF AD pathologies over time in MCI subjects. At baseline, there were 870 subjects with MCI, including 618 non-smokers (no history of smoking) and 252 smokers (any lifetime history of smoking). Linear mixed models were fitted for each outcome with adjustment of several covariates. The major findings were: (1) Among older people with MCI, smokers showed faster decline in functional performance compared to non-smokers; (2) Smokers demonstrated steeper decline in entorhinal cortex volume than non-smokers; (3) A history of cigarette smoking was not associated with change in CSF Aβ42, t-tau or p-tau levels over time in MCI subjects. In conclusion, we found that a history of cigarette smoking was associated with faster decline in functional performance and entorhinal cortex volume over time at the prodromal stage of dementia.

Relationship Between Depression/Anxiety and Cognitive Function Before and 6 Weeks After Major Non-Cardiac Surgery in Older Adults.

To determine the relationship between affective measures and cognition before and after non-cardiac surgery in older adults. Observational prospective cohort study in 103 surgical patients age ≥ 60 years old. All participants underwent cognitive testing, Center for Epidemiologic Studies-Depression, and State Anxiety Inventory screening before and 6 weeks after surgery. Cognitive test scores were combined by factor analysis into 4 cognitive domains, whose mean was defined as the continuous cognitive index (CCI). Postoperative global cognitive change was defined by CCI change from before to after surgery, with negative CCI change indicating worsened postoperative global cognition and vice versa. Lower global cognition before surgery was associated with greater baseline depression severity (Spearman's r = -0.30, p = 0.002) and baseline anxiety severity (Spearman's r = -0.25, p = 0.010), and these associations were similar following surgery (r = -0.36, p < 0.001; r = -0.26, p = 0.008, respectively). Neither baseline depression or anxiety severity, nor postoperative changes in depression or anxiety severity, were associated with pre- to postoperative global cognitive change. Greater depression and anxiety severity were each associated with poorer cognitive performance both before and after surgery in older adults. Yet, neither baseline depression or anxiety symptoms, nor postoperative change in these symptoms, were associated with postoperative cognitive change.

Neuropsychiatric symptoms and cognitive trajectories in older adults free of dementia: The Mayo Clinic Study of Aging

AbstractBackgroundNeuropsychiatric symptoms (NPS) are associated with the risk of incident mild cognitive impairment (MCI) and dementia. However, the association between NPS and global and domain‐specific cognitive trajectories among older adults free of dementia remains unclear.MethodWe conducted a longitudinal study derived from the population‐based Mayo Clinic Study of Aging, including individuals aged ≥ 50 years who were free of dementia. Participants completed the Neuropsychiatric Inventory Questionnaire at baseline and underwent neuropsychological testing assessing four cognitive domains (i.e., memory, language, attention, visuospatial skills) every 15 months. We calculated linear mixed‐effect models with random subject‐specific intercepts and slopes to examine the association between presence of twelve different NPS (i.e., delusions, hallucinations, agitation, depression, anxiety, euphoria, apathy, disinhibition, irritability, motor behavior, nighttime behavior, appetite) at baseline and trajectories for individual yearly change in global and domain‐specific cognitive z‐scores. The models were adjusted for age, sex, education, and whether or not this was the first time the cognitive battery had been administered.ResultThe sample included 5081 persons (51% males; 4439 cognitively unimpaired, 642 with MCI). The median [IQR] age was 74 [67, 81] years, and the median [IQR] education was 14 [12, 16] years. Regardless of NPS status, participants declined in cognition over time, on average. However, presence of NPS was significantly associated with an increased decline in cognition, i.e., the annualized change in global cognition z‐scores for participants with compared to without the given NPS ranged from ‐0.018 (p = 0.011) for irritability to ‐0.16 (p = 0.001) for hallucinations. These associations between NPS and annual decline in global cognition were significant for all NPS except euphoria and disinhibition. Similar results were seen for the individual cognitive domains, e.g., participants with depression, apathy and nighttime behavior had a greater longitudinal decline in all domain specific z‐scores, whereas presence of delusions and anxiety was associated with a more pronounced decline in language, attention and visuospatial skills.ConclusionNeuropsychiatric symptoms are associated with greater longitudinal decline of both global and domain‐specific cognitive functions in community‐dwelling older adults free of dementia. More research is needed to confirm these preliminary findings.

Single nucleus and bulk homogenate RNA‐sequencing comparison of vascular endothelial growth factor family associations with Alzheimer's disease

AbstractBackgroundPrevious work from our group and others has suggested that the VEGF family of genes and proteins may be involved in the pathophysiology of Alzheimer’s disease (AD) and associated cognitive decline. Using dorsolateral prefrontal cortex (DLPFC) RNA sequencing (RNA‐seq) data (N = 531), we have characterized robust associations between gene expression of four family members (VEGFB, PGF, FLT1 and FLT4) and AD diagnosis, neuropathology, and associated cognitive decline. More specifically, increased brain expression of these genes was associated with worse outcomes. Single nucleus RNA sequencing (snRNA‐seq) of DLPFC became available for a small subset of this cohort (N = 48). We set out to assess associations between gene expression of these family members and cognitive decline using snRNA‐seq and compare to homogenate RNA‐seq findings to better understand the cell specificity of observed effects.MethodLongitudinal cognitive and snRNA‐seq data from astrocytes, endothelial cells, microglia, oligodendrocytes, oligodendrocyte progenitor cells, pericytes, excitatory and inhibitory neurons were obtained from the Religious Orders Study and Rush Memory and Aging Project cohort studies. Linear regression and mixed‐effects regression were used to assess VEGF gene expression associations with global cognition and cognitive change, respectively. Models covaried for age at death, sex and postmortem interval and were subjected to the Benjamini‐Hochberg procedure to correct for multiple comparisons within cell types.ResultPGF and FLT4 expression across cell types was too low to be considered in statistical models. FLT1 expression was largely restricted to endothelial cells. while VEGFB expression was highest in neurons and astrocytes. Interestingly, inhibitory neuron VEGFB expression approached a positive association with cross‐sectional cognition (p.fdr = 0.055), in opposition to the direction of our bulk homogenate finding. In contrast, oligodendrocyte VEGFB was negatively associated with cross‐sectional (p.fdr = 0.039) and longitudinal (p.fdr = 0.053) cognition, consistent with our previous findings in bulk.ConclusionSingle nucleus VEGF expression analyses suggest that homogenate VEGFB associations with AD outcomes are driven by oligodendrocytes. VEGFB is a neuroprotective factor, and the observed upregulation in VEGFB could represent a stress response to AD pathology. The highly restricted expression of FLT1 to endothelial cells suggests that the relationship between FLT1 and cognitive trajectory reflects alterations in endothelial signaling.

Physical Activity and Trajectory of Cognitive Change in Older Persons: Mayo Clinic Study of Aging.

Background:Little is known about the association between physical activity (PA) and cognitive trajectories in older adults.Objective:To examine the association between PA and change in memory, language, attention, visuospatial skills, and global cognition, and a potential impact of sex or Apolipoprotein E (APOE) ɛ4 status.Methods:Longitudinal study derived from the population-based Mayo Clinic Study of Aging, including 2,060 cognitively unimpaired males and females aged ≥70 years. Engagement in midlife (ages 50–65) and late-life (last year) PA was assessed using a questionnaire. Neuropsychological testing was done every 15 months (mean follow-up 5.8 years). We ran linear mixed-effect models to examine whether mid- or late-life PA at three intensities (mild, moderate, vigorous) was associated with cognitive z-scores.Results:Light intensity midlife PA was associated with less decline in memory function compared to the no-PA reference group (time x light PA; estimate [standard error] 0.047 [0.016], p = 0.004). Vigorous late-life PA was associated with less decline in language (0.033 [0.015], p = 0.030), attention (0.032 [0.017], p = 0.050), and global cognition (0.039 [0.016], p = 0.012). Females who were physically inactive in midlife experienced more pronounced cognitive decline than females physically active in midlife and males regardless of PA (p-values for time interaction terms with midlife PA levels and sex were all p < 0.05 for global cognition). APOE ɛ4 carriership did not moderate the association between PA and cognition.Conclusion:Engaging in PA, particularly of vigorous intensity in late-life, was associated with less pronounced decline in global and domain-specific cognition. This association may differ by sex.