Decline In Global Cognitive Function Research Articles

Effects of Virtual Reality Physical and Cognitive Training Intervention On Cognitive Abilities of Elders with Mild Cognitive Impairment.

Virtual reality (VR) technology has become increasingly used for assessment and intervention in the neuroscience field. We aimed to investigate the effects of a VR Training System, named VRADA (VR Exercise App for Dementia and Alzheimer's Patients), on the cognitive functioning of older people with mild cognitive impairment (MCI). In this intervention study, 122 older adults with MCI were randomly assigned to five groups (the VRADA group (n = 28), a bike group (n = 11), a physical exercise group (n = 24), a mixed group (physical and cognitive exercise) (n = 31), and a non-contact control group (n = 28). The VRADA group underwent 32 physical and cognitive training sessions, performed 2 or 3 times weekly for 12 weeks in the VR environment. All participants had detailed neuropsychological assessments before and after intervention. A series of linear regression models revealed that the VRADA group showed improvement or no deterioration in cognitive decline in global cognitive function (MMSE), verbal memory (Rey Auditory Verbal Learning Test and WAIS forward test), and executive functions, mental flexibility (Trail Making Test B). This interventionstudy indicates that the VRADA system improves the cognitive function of elders with MCI.

Association of cognitive reserve indicator with cognitive decline and structural brain differences in mid‐ and late life: a large population‐based cohort study

AbstractBackgroundCognitive reserve (CR) contributes to preserving cognition when facing brain aging and damage. CR has been linked to reduced dementia risk in late life. However, the association between CR and brain imaging measures, especially in mid‐life, is unclear. We aimed to explore the association of CR with cognitive decline and structural brain differences in mid‐ and late life.MethodWithin the UK Biobank, 42,301 dementia‐free participants aged 40‐70 were followed for a median of 9 (interquartile range: 8 to 10) years. Latent class analysis was used to generate an indicator of CR (categorized as high, moderate, and low) based on education, occupation, and multiple cognitively stimulating activities at baseline. Cognitive tests for global and domain‐specific cognitive function were administrated at baseline and follow‐up. A subsample (n = 34,041) underwent brain magnetic resonance imaging (MRI) scans at the follow‐up examination. Volumes of total brain, white matter, grey matter, hippocampus, and white matter hyperintensities (TBV, WMV, GMV, HV, and WMHV) were assessed. Data were analyzed using mixed‐effects models and linear regression.ResultAt baseline, 16,032 (37.90%), 10,709 (25.32%), and 15,560 (36.78%) participants had low, moderate, and high levels of CR, respectively. In multi‐adjusted mixed‐effects models, compared to low CR, high CR was associated with a slower decline in global cognitive function (β [95% confidence interval, CI]: 0.10 [0.08, 0.11]), prospective memory (0.10 [0.06, 0.15]), fluid intelligence (0.07 [0.04, 0.10]), and reaction time (0.04 [0.02, 0.06]). In MRI data analysis, high CR was related to lesser TBV (‐0.03 [‐0.04, ‐0.02]), WMV (‐0.03 [‐0.04, ‐0.02], GMV (‐0.02 [‐0.04, ‐0.01]), and WMHV (‐0.03 [‐0.05, ‐0.002]), but greater HV (0.04 [0.02, 0.06]) compared to low CR. In analyses stratified by baseline age, the significant associations between high CR and global cognition and TBV were present among both mid‐life (<60 years) and late‐life (≥60 years) participants. The CR‐cognitive decline association remained significant after additional adjustment for MRI measures.ConclusionHigher CR is associated with slower cognitive decline, lesser TBV, greater HV, and lower microvascular burden, especially in mid‐life. The protective role of high CR on cognition is independent of structural brain differences.

Cardiometabolic disease, cognitive decline, and structural brain differences in mid‐ and late‐life: a large population‐based cohort study

AbstractBackgroundThe impact of cardiometabolic diseases (CMDs; including type 2 diabetes [T2D], heart disease [HD], and stroke) on cognitive trajectories and brain structural changes across the life course is unclear. We aimed to explore the association of patterns of co‐morbid CMDs with cognitive decline and structural brain MRI measures in mid‐ vs. late‐ life.MethodWithin the UK Biobank, 46,562 dementia‐free participants aged 40‐70 were followed for 9 years. Baseline CMDs were ascertained medical records. A battery of 5 cognitive tests was administered at baseline and follow‐up and used to derive global and domain‐specific cognitive function scores. A subsample (n = 39,353) underwent brain magnetic resonance imaging (MRI) scans at the follow‐up examination. Volumes of total brain, white matter, grey matter, hippocampus, and white matter hyperintensities (TBV, WMV, GMV, HV, and WMHV) were assessed. Data were analyzed using multivariate adjusted mixed‐effects models and linear regression.ResultAt baseline, 3,437 (7.4%) participants had 1 CMD and 297 (0.6%) had ≥2. In mixed‐effects models, the presence of any CMD was related to a steeper decline in global cognitive function (β [95% confidence interval]: ‐0.005 [‐0.008, ‐0.003]) as well as working memory (‐0.024 [‐0.033, ‐0.014]), visual declarative memory (‐0.004 [‐0.007, ‐0.001]), and processing speed (‐0.002 [‐0.002, ‐0.001]), especially for those with CMD profiles involving T2D and/or HD. In stratified analysis by age (mid‐ [<60] vs. late‐ [≥60] life), CMDs were related to a decline in only processing speed in mid‐life, while in late‐life, CMDs were additionally related to a decline in verbal/numeric reasoning. In linear regression, people with CMDs had significantly lower TBV (‐0.15 [‐0.18, ‐0.12]), GMV (‐0.17 [‐0.20, ‐0.14]), WMV (‐0.11 [‐0.14, ‐0.08]), HV (‐0.14 [‐0.18, ‐0.11]) and significantly higher WMH (0.05 [0.02, 0.09]), and this was exacerbated among people with ≥2 CMDs compared to 1 CMD. Similar results were observed in both mid‐ and late‐life.ConclusionThe presence of CMDs is associated global/domain‐specific cognitive decline and brain MRI measures involving neurodegenerative and vascular markers in both mid‐ and late‐ life. Our findings highlight the need for the effective management of CMDs in mid‐life for the prevention of dementing disorders in late‐life.

Effects of asymptomatic cerebral artery stenosis of anterior circulation and establishment of collateral circulation on cognition

ObjectiveThe purpose of this study is to investigate how cognition is affected by asymptomatic cerebral artery stenosis (CAS) of the anterior circulation and its related collateral circulation. Methods102 patients with CAS of the anterior circulation and 52 controls were enrolled from January 1, 2019 to June 30, 2022. Patients with CAS of anterior circulation were further divided into different subgroups according to the degree of stenosis, cerebral perfusion, and collateral circulation. A series of neuropsychological scales were used to evaluate the participant’s cognitive function, activities of daily living, and neuropsychiatric symptoms (such as memory, execution, psychomotor speed, etc.). The data were analyzed using T-test, F-test, chi-square test, rank sum test, and other statistical methods, moreover, the quantitative data were further examined for trends. The relationship between the degree of CAS, cerebral perfusion, collateral circulation, and the outcome of the cognitive test was investigated using Spearman correlation analysis. ResultsCompared to controls, there were severe impairments of global cognition, psychomotor speed/execution, memory, attention, activities of daily living, and more neuropsychiatric symptoms in patients with anterior circulation CAS (p < 0.05), and these impairments got worsened with the aggravation of CAS (p < 0.05). The global cognition, psychomotor speed / executive function, memory function, and daily living ability were impaired both in the cerebral perfusion-compensated group and decompensated group(p < 0.05), while there was no statistically significant difference between the two groups (p > 0.05). With the aggravation of CAS, the proportion of poor collateral formation increased, and this difference was statistically significant (P < 0.01). The degree of stenosis, cerebral perfusion, and collateral circulation establishment of anterior circulation CAS was correlated with global cognition, memory, psychomotor speed, execution, attention, activities of daily living, and neuropsychiatric symptoms (all p < 0.01). ConclusionCognitive impairment and the percentage of inadequate collateral circulation development rise as stenosis progresses in patients with anterior circulation CAS. The decline in global cognitive function was accompanied by impairments in psychomotor speed / executive function, memory function, attention, and daily living skills, as well as the aggravation of neuropsychiatric symptoms, especially in patients with impaired cerebral perfusion and poor collateral circulation formation.

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.

Loneliness and cognitive decline in the community: Examining demographic and APOE4 status differences

AbstractBackgroundLimited information exists regarding patterns of loneliness and relationships among subgroups of older adults in the community. We evaluated demographic and APOE4 status differences in associations between loneliness and cognitive decline in older adults.MethodParticipants (N = 7,696) were selected from the Chicago Health and Aging Project (CHAP), a longitudinal population‐based study, who completed at least two measurement time points of neuropsychological testing, including individual tests of episodic memory, perceptual speed, and the Mini‐Mental State Examination (MMSE). The mean of individual test scores was taken to calculate composite global cognitive function. Loneliness was measured using an item from the Center for Epidemiologic Studies‐Depression Scale (modified). Mixed effects regression models evaluated associations between loneliness and decline in global cognitive function and individual tests, by race, sex, and APOE4 (one or more copies of e4 allele (any) vs. none). Modeling included adjustments such as sex, race, age, education, chronic conditions, cognitive activities, statin prescription, and interactions with time for each.ResultA higher percentage of participants that were female (74% vs. 61%), African American compared to Non‐Hispanic White (72% vs. 63%), with older mean age (74 vs. 72 years) reported loneliness. The prevalence of loneliness was similar across APOE4 status. The interaction/ synergy of loneliness with time had statistically significant associations with global cognition (β = ‐0.010, p = 0.005), episodic memory (β = ‐0.010, p = 0.017), and MMSE (β = ‐0.015, p = 0.000) for women. This interaction was statistically significant in associations with global cognition (β = ‐0.012, p = 0.001), episodic memory (β = ‐0.011, p = 0.012), and MMSE (β = ‐0.018, p = 0.000) among African American participants. This interaction also showed the following statistically significant associations by APOE4 status: any (β = ‐0.012, p = 0.034) and none (β = ‐0.007, p = 0.049) for global cognition, none (β = ‐0.009, p = 0.039) for episodic memory, and any (β = ‐0.017, p = 0.009) and none (β = ‐0.011, p = 0.004) for MMSE.ConclusionLoneliness is differentially associated with global cognitive decline based on race and sex but not APOE4 status. More research is needed to understand relationships between loneliness and biological mechanisms and how to best account for demographic characteristics when intervening on loneliness.

Meta-analysis of age-related cognitive decline reveals a novel locus for the attention domain and implicates a COVID-19-related gene for global cognitive function.

Cognitive abilities have substantial heritability throughout life, as shown by twin- and population-based studies. However, there is limited understanding of the genetic factors related to cognitive decline in aging across neurocognitive domains. We conducted a meta-analysis on 3045 individuals aged ≥65, derived from three population-based cohorts, to identify genetic variants associated with the decline of five neurocognitive domains (attention, memory, executive function, language, visuospatial function) and global cognitive decline. We also conducted gene-based and functional bioinformatics analyses. Apolipoprotein E (APOE)4 was significantly associated with decline of memory (p=5.58E-09) and global cognitive function (p=1.84E-08). We identified a novel association with attention decline on chromosome 9, rs6559700 (p=2.69E-08), near RASEF. Gene-based analysis also identified a novel gene, TMPRSS11D, involved in the activation of SARS-CoV-2, to be associated with the decline in global cognitive function (p=4.28E-07). Domain-specific genetic studies can aid in the identification of novel genes and pathways associated with decline across neurocognitive domains. rs6559700 was associated with decline of attention. APOE4 was associated with decline of memory and global cognitive decline. TMPRSS11D, a gene involved in the activation of SARS-CoV-2, was implicated in global cognitive decline. Cognitive domain abilities had both unique and shared molecular pathways across the domains.

Cognitive and physical declines and falls in older people with and without mild cognitive impairment: a 7-year longitudinal study.

We examined longitudinal changes in cognitive and physical function and associations between change in function and falls in people with and without mild cognitive impairment (MCI). Prospective cohort study with assessments every 2 years (for up to 6 years). Community, Sydney, Australia. Four hundred and eighty one people were classified into three groups: those with MCI at baseline and MCI or dementia at follow-up assessments (n = 92); those who fluctuated between cognitively normal and MCI throughout follow-up (cognitively fluctuating) (n = 157), and those who were cognitively normal at baseline and all reassessments (n = 232). Cognitive and physical function measured over 2-6 years follow-up. Falls in the year following participants' final assessment. In summary, 27.4%, 38.5%, and 34.1% of participants completed 2, 4, and 6 years follow-up of cognitive and physical performance, respectively. The MCI and cognitive fluctuating groups demonstrated cognitive decline, whereas the cognitively normal group did not. The MCI group had worse physical function than the cognitively normal group at baseline but decline over time in physical performance was similar across all groups. Decline in global cognitive function and sensorimotor performance were associated with multiple falls in the cognitively normal group and decline in mobility (timed-up-and-go test) was associated with multiple falls across the whole sample. Cognitive declines were not associated with falls in people with MCI and fluctuating cognition. Declines in physical function were similar between groups and decline in mobility was associated with falls in the whole sample. As exercise has multiple health benefits including maintaining physical function, it should be recommended for all older people. Programs aimed at mitigating cognitive decline should be encouraged in people with MCI.

Obstructive sleep apnoea and 5-year cognitive decline in the elderly.

The relationship between obstructive sleep apnoea (OSA) and cognitive decline remains controversial, especially in the elderly population. We used data from the HypnoLaus study to assess associations between OSA and longitudinal cognitive changes in a sample of community-dwelling elderly individuals. We studied associations between polysomnographic OSA parameters (of breathing/hypoxaemia and sleep fragmentation) and cognitive changes over a 5-year period, after adjustment for potential confounders. The primary outcome was the annual change in cognitive scores. The moderating effects of age, sex and apolipoprotein E4 (ApoE4) status were also examined. 358 elderly individuals without dementia were included (mean±sd age 71.0±4.2 years; 42.5% males). A lower mean peripheral oxygen saturation (S pO2 ) during sleep was associated with a steeper decline in Mini-Mental State Examination (B= -0.12, p=0.004), Stroop test condition 1 (B=0.53, p=0.002) and Free and Cued Selective Reminding Test delayed free recall (B= -0.05, p=0.008). A longer time spent asleep with S pO2 <90% was associated with a steeper decline in Stroop test condition 1 (B=0.47, p=0.006). Moderation analysis showed that apnoea-hypopnoea index and oxygen desaturation index were associated with a steeper decline in global cognitive function, processing speed and executive function only in older participants, men and ApoE4 carriers. Our results provide evidence of the contribution of OSA and nocturnal hypoxaemia to cognitive decline in the elderly population.

Race and Apolipoprotein E-e4 Allele Status Differences in the Association Between Loneliness and Cognitive Decline.

This study aimed to examine race and apolipoprotein E-e4 allele (APOE-e4) status differences in the longitudinal associations between loneliness and cognitive decline. The study sample is composed of participants ( N = 7696, 64% Black participants and 36% White participants) from the Chicago Health and Aging Project, a population-based cohort study. Mixed-effects regression models were conducted to examine the longitudinal associations between loneliness on global cognitive function and individual tests of cognitive function. Models were also stratified by race and APOE-e4. A greater percentage of Black participants (17%) reported loneliness at baseline visit compared with White participants (12%). Black and White participants who were lonely individuals had a similar rate of decline in global cognitive function at 0.075 (95% confidence interval [CI] = -0.082 to -0.068) standard deviation unit (SDU) per year for Black participants and at 0.075 (95% CI = -0.086 to -0.063) SDU per year for White participants. Lonely participants with APOE-e4 had a higher rate of global cognitive decline at -0.102 (95% CI = -0.115 to -0.088) SDU per year than for lonely participants without APOE-e4 at -0.052 (95% CI = -0.059 to -0.045) SDU per year. The burden of loneliness and its relation to cognitive decline is higher among participants with APOE-e4 compared with those without APOE-e4. Loneliness is associated with cognitive decline in both Black and White participants.

Physical Frailty and Cognitive Function among Older Chinese Adults: The Mediating Roles of Activities of Daily Living Limitations and Depression.

Physical frailty and cognitive impairment are prevalent globally, particularly in China, which is experiencing an unprecedented aging of its large population. Examine the association between physical frailty and the level and rate of change of cognitive function, globally and by domain, among community-dwelling Chinese older adults, and quantify the mediation effects from activities of daily living (ADL) limitations and depressive symptoms. Longitudinal. China Health and Retirement Longitudinal Study (2011-2018). 5,431 eligible adults aged ≥ 60 years with valid information on physical frailty. Physical frailty, cognitive function, ADL limitations, and depressive symptoms were respectively assessed by frailty phenotypes, the Telephone Interview for Cognitive Status (episodic memory, executive function, and orientation), performance in six daily tasks, and the eight-item Center for Epidemiological Studies Depression Scale. Latent growth curve models were used to address the objectives. Compared to adults who were non-frail, those who were pre-frail (β = -0.06) and frail (β = -0.13) reported significantly worse global cognitive function and episodic memory (pre-frail: β = -0.05; frail: β = -0.14), executive function (pre-frail: β = -0.04, frail: β = -0.10), and orientation (pre-frail: β = -0.06; frail: β = -0.07) at baseline; those who were frail were more likely to experience faster decline in global cognitive function (β = 0.12) and episodic memory (β = 0.08). ADL limitations (β = -0.07) and depressive symptoms (β = -0.14) significantly mediated the association between physical frailty and the level of cognitive function, but not its rate of decline. Intervention strategies that help maintain cognitive function may benefit from early screening and assessment of physical frailty. For pre-frail and frail older Chinese adults, programs designed to help improve or maintain activities of daily living and reduce number of depressive symptoms may contribute to better cognitive performance.

Associations of audiometric hearing and speech-in-noise performance with cognitive decline among older adults: The Baltimore Longitudinal Study of Aging (BLSA).

Established associations between hearing loss and cognitive decline were primarily defined by pure-tone audiometry, which reflects peripheral hearing ability. Speech-in-noise performance, which reflects central hearing ability, is more limited in prior literature. We examined the longitudinal associations of audiometric hearing and speech-in-noise performance with cognitive decline. We studied 702 participants aged ≥60 years in the Baltimore Longitudinal Study of Aging 2012-2019. Global and domain-specific (language, memory, attention, executive function, visuospatial ability) cognitive performance were assessed by the cognitive assessment battery. Hearing thresholds at 0.5, 1, 2, and 4 kilohertz obtained from pure-tone audiometry were averaged to calculate better-ear pure-tone average (PTA) and participants were categorized as having hearing loss (>25 decibels hearing level [dB HL]) or normal hearing (≤25 dB HL). Speech-in-noise performance was assessed by the Quick Speech-in-Noise (QuickSIN) test, and participants were categorized as having below-median (worse) or above-median performance. Linear mixed effects models with random intercepts and slopes were used to assess baseline cognitive performance and cognitive decline by hearing status. Models adjusted for demographic, lifestyle and disease factors. Participants with audiometric hearing loss showed similar baseline cognitive performance but faster decline in global cognitive function, language, executive function, and attention. Participants with below-median QuickSIN score showed worse baseline cognitive performance in all domains and faster decline in global cognitive function, language, memory, executive function and attention. Audiometric hearing might be targeted to delay cognitive decline. Speech-in-noise performance might be a novel marker and might be more sensitive to memory decline.

Distressing dreams, cognitive decline, and risk of dementia: A prospective study of three population-based cohorts.

SummaryBackgroundDistressing dreams are associated with faster cognitive decline and increased dementia risk in people with Parkinson's disease (PD). Whether distressing dreams might be associated with cognitive decline and dementia in people without PD is unknown. This study investigated the association between self-reported distressing dream frequency and the risk of cognitive decline and incident dementia in community-dwelling men and women without cognitive impairment or PD.MethodsRisk of cognitive decline was evaluated in 605 middle-aged adults (mean age = 50 years [IQR 44–57]; 55·7% female) from the Midlife in the United States (MIDUS) study, who were cognitively normal at baseline, and were followed-up for a maximum of 13 years (IQR 9–10). Cognitive decline was defined as having an annual rate of decline in global cognitive function (measured using five cognitive tests) ≥ 1 standard deviation faster than the mean decline rate from baseline to follow-up. Risk of incident all-cause dementia was evaluated in 2600 older adults (mean age = 83 years [IQR 81–84]; 56·7% female) pooled from the Osteoporotic Fractures in Men Study (MrOS) and the Study of Osteoporotic Fractures (SOF), who were dementia-free at baseline, and were followed-up for up a maximum of 7 years (IQR 4–5). Incident dementia was based on doctor-diagnosis. Frequency of distressing dreams was assessed in all cohorts at baseline (January 2002 – March 2012) using item 5h of the Pittsburgh Sleep Quality Index. The association between self-reported distressing dream frequency (“never”, “less than weekly”, “weekly”) and later cognitive outcomes, was evaluated using multivariable logistic regression in both the middle-aged and pooled older adult cohorts.FindingsAfter adjustment for all covariates, a higher frequency of distressing dreams was linearly and statistically significantly associated with higher risk of cognitive decline amongst middle-aged adults (P for trend = 0·016), and higher risk of incident all-cause dementia amongst older adults (P for trend <0·001). Compared with middle-aged adults who reported having no distressing dreams at baseline, those who reported having weekly distressing dreams had a 4-fold risk of experiencing cognitive decline (adjusted odds ratio [aOR] = 3·99; 95% CI: 1·07, 14·85). Amongst older adults, the difference in dementia risk was 2·2-fold (aOR = 2·21; 95% CI: 1·35, 3·62). In sex-stratified analyses, the associations between distressing dreams and both cognitive outcomes were only statistically significant amongst men.InterpretationDistressing dreams predict cognitive decline and all-cause dementia in middle-aged and older adults without cognitive impairment or PD - especially amongst men. These findings may help to identify individuals at risk of dementia and could facilitate early prevention strategies.FundingThe study received no external funding.

Development of cerebral microbleeds and its impact on cognitive function in adult patients receiving medical management alone for ischemic moyamoya disease: supplementary analysis of a 5-year prospective cohort

ABSTRACT Objective De novo cerebral microbleeds (CMBs) on T2*-weighted magnetic resonance imaging (MRI) develop over time in adult moyamoya disease (MMD) and are generally associated with a decline in global cognitive function. The present supplementary analysis of a 5-year prospective cohort aimed to elucidate the incidence of an interval increase in CMBs in adult patients receiving medical management alone for ischemic MMD and its impact on cognitive function. Methods Sixty-four patients without misery perfusion in the symptomatic cerebral hemispheres at inclusion who did not experience any further ischemic symptoms or new hemorrhagic events during a 5-year follow-up period underwent T2*-weighted MRI and five kinds of neuropsychologic tests at inclusion and the end of the 5-year follow-up. Results When T2*-weighted MRI was compared between inclusion and the end of the 5-year follow-up, 10 patients (15%) had an interval increase in CMBs in the symptomatic cerebral hemisphere at inclusion. The scores from two kinds of neuropsychologic tests significantly deteriorated at the end of the 5-year follow-up compared with those at inclusion in patients with an interval increase in CMBs, whereas the scores of four kinds of neuropsychologic tests significantly improved at the end of the 5-year follow-up compared with those at inclusion in patients without interval increases in CMBs, asymptomatic ischemic lesions, or angiographic disease progression. Conclusions The incidence of an interval increase in CMBs was 15% per 5 years in adult patients receiving medical management alone for ischemic MMD, and this increase was associated with a decline in cognitive decline.

Associations between trajectories of depressive symptoms and rate of cognitive decline among Chinese middle-aged and older adults: An 8-year longitudinal study

ObjectiveTo investigate the associations between trajectories of depressive symptoms and rate of cognitive decline among Chinese middle-aged and older adults. MethodsA population-based cohort data from the Chinese Health and Retirement Longitudinal Study (CHARLS) were utilized. The cohort was followed up for 8 years and assessments of depressive symptoms and cognitive performance were conducted in 2011, 2013, 2015, and 2018. Group-based trajectory modeling (GBTM) was conducted to identify heterogeneous trajectories of depressive symptoms. Linear mixed models (LMMs) were performed to examine the associations between trajectories of depressive symptoms and rate of decline in global cognitive function, episodic memory, and executive function. ResultsAmong 9264 middle-aged and older adults, five depressive symptoms trajectory groups were determined: constantly low (n = 3206, 34.6%), constantly medium (n = 3747, 40.5%), increasing (n = 899, 9.7%), decreasing (n = 929, 10.0%), and constantly high (n = 483, 5.2%). Individuals with increasing depressive symptoms exhibited the fastest decline in global cognitive function and episodic memory, followed by participants reporting constantly high or medium depressive symptoms. A significantly higher rate of decline in executive function was only observed among subjects who had increasing depressive symptoms in comparison with their counterparts with constantly low depressive symptoms. There was no significant difference in rate of cognitive decline between individuals with decreasing depressive symptoms and those demonstrating constantly low depressive symptoms. ConclusionIncreasing depressive symptoms co-occurred with the steepest cognitive decline among Chinese middle-aged and older adults, which potentially suggested that interventions targeting to alleviating cognitive decline should be given priority among individuals with deterioration of depressive symptoms.

Dairy Product Consumption and Changes in Cognitive Performance: Two-Year Analysis of the PREDIMED-Plus Cohort.

ScopeDairy consumption has been suggested to impact cognition; however, evidence is limited and inconsistent. This study aims to longitudinally assess the association between dairy consumption with cognitive changes in an older Spanish population at high cardiovascular disease risk.Methods and resultsFour thousand six hundred sixty eight participants aged 55–75 years, completed a validated food frequency questionnaire at baseline and a neuropsychological battery of tests at baseline and 2‐year follow‐up. Multivariable linear regression models are used, scaled by 100 (i.e., the units of β correspond to 1 SD/100), to assess associations between baseline tertile daily consumption and 2‐year changes in cognitive performance. Participants in the highest tertile of total milk and whole‐fat milk consumption have a greater decline in global cognitive function (β: –4.71, 95% CI: –8.74 to –0.69, p‐trend = 0.020 and β: –6.64, 95% CI: –10.81 to –2.47, p‐trend = 0.002, respectively) compared to those in the lowest tertile. No associations are observed between low fat milk, yogurt, cheese or fermented dairy consumption, and changes in cognitive performance.ConclusionResults suggest there are no clear prospective associations between consumption of most commonly consumed dairy products and cognition, although there may be an association with a greater rate of cognitive decline over a 2‐year period in older adults at high cardiovascular disease risk for whole‐fat milk.

The Clinical Course of Early and Late Mild Cognitive Impairment.

IntroductionAmnestic mild cognitive impairment (MCI) can be classified as either early MCI (EMCI) or late MCI (LMCI) according to the severity of memory impairment. The aim of this study was to compare the prognosis and clinical course between EMCI and LMCI.MethodsBetween January 2009 and December 2017, a total of 418 patients with MCI and 146 subjects with normal cognition were recruited from a memory clinic. All the patients received at least two series of neuropsychological evaluations each year and were categorized as either EMCI or LMCI according to Alzheimer's Disease Neuroimaging Initiative 2 (ADNI2) criteria.ResultsIn total, our study included 161 patients with EMCI, 258 with LMCI, and 146 subjects with normal cognition as controls (NCs). The mean follow-up duration was 3.55 ± 2.18 years (range: 1–9). In a first-year follow-up assessment, 54 cases (32.8%) of EMCI and 16 (5%) of LMCI showed a normal cognitive status. There was no significant difference between the first year EMCI reverter and NCs in terms of dementia-free survival and further cognitive decline. However, first-year LMCI reverters still had a higher risk of cognitive decline during the following evaluations. Until the last follow-up, annual dementia conversion rates were 1.74, 4.33, and 18.6% in the NC, EMCI, and LMCI groups, respectively. The EMCI and LMCI groups showed a higher rate of progression to dementia (log-rank test, p < 0.001) than normal subjects. Compared with NCs, patients in the LMCI group showed a significantly faster annual decline in global cognition [annual rate of change for the mini-mental status examination (MMSE) score: −1.035, p < 0.001]) and all cognitive domains, while those in the EMCI group showed a faster rate of decline in global cognitive function (annual rate of change for the MMSE score: −0.299, p = 0.001).ConclusionIt is important to arrange follow-up visits for patients with MCI, even in the EMCI stage. One-year short-term follow-up may provide clues about the progression of cognitive function and help to identify relatively low-risk EMCI subjects.

Low folate predicts accelerated cognitive decline: 8-year follow-up of 3140 older adults in Ireland.

To examine associations of plasma folate concentrations and risk of global and domain-specific cognitive decline in older people. Data of 3140 participants from The Irish Longitudinal Study on Ageing (TILDA), a nationally-representative cohort of adults aged ≥50 years were used over 8-year follow-up. Biannual cognitive assessments included the Mini-Mental State Examination (MMSE), verbal fluency and immediate and delayed word recall tests (Waves 1-5) and the Montreal Cognitive Assessment, (MoCA) (Waves 1 and 3). Plasma folate concentrations were measured in stored blood collected at baseline. Mixed effects Poisson and linear regression determined associations between baseline folate concentrations and cognition. In multivariable-adjusted models of those aged ≥50 years at baseline, low folate at baseline (<11.2 nmol/L) was associated with higher proportions of MMSE errors (incidence rate ratio [IRR] = 1.10; 95% confidence interval [CI] (1.00, 1.21), lowest vs. highest quintile) over 8 years. Plasma folate <21.8 nmol/L predicted declines in episodic memory for immediate (beta [β] = -0.26; 95% CI (-0.48, -0.03), β = -0.29; 95% CI (-0.50, 0.08) and β = -0.29; (-0.50, -0.08), for lowest three vs. highest quintile) and delayed recall (β = -0.20; 95% CI (-0.38, -0.01), β = -0.18; 95% CI (-0.37, -0.01) and β = -0.19; (-0.36, -0.01) lowest three vs. highest quintile). There were no significant associations in a subsample aged ≥65 years. In those aged ≥50 years, lower concentrations of folate may have differential relationships with cognitive domains. Folate <11.2 nmol/L predicted a decline in global cognitive function, while <21.8 nmol/L predicted poorer episodic memory. Low folate was associated with accelerated decline in cognitive function and is an important marker for cognitive decline among older people.

Higher angiotensin II type 1 receptor (AT1 R) levels and activity in the postmortem brains of older persons with Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia. Although multiple potential etiologies have been proposed, no clear aging-related etiological mechanisms have been identified. Renin Angiotensin system (RAS) is a hormonal system that is implicated in blood pressure control and has been suggested as a potential contributor to the development of AD. Here, using postmortem frontal cortex brain samples of age- and sex-matched cognitively normal individuals (n=30) and AD patients (n=30), we sought to examine the brain specific RAS (b-RAS) differences with AD and how these findings correlate with brain AD pathologies. Samples were obtained from the Rush Memory and Aging Project. We measured angiotensinogen, renin, and ACE gene expression by qPCR and both gene expression and protein levels of Angiotensin II receptor type 1, 2, and 4 and their downstream signaling pathway (pERK, eNOS, and nNOS) by qPCR and Western blot. Brain cytokines (IL6, TNFα, IFNγ, and IL1β) and oxidative stress (OS) marker (protein carbonyl) as well as average paired helical filaments-tau and β-amyloid load were used as specific markers of AD pathology. Our results demonstrate an increase in both gene and protein expression (2.47 folds p=0.01, median0.59 (range1.99) vs. 0.47 (1.95) p=0.03, respectively) and signaling activity (0.35 (11.41) vs. 0.04 (1.84), p<0.01) of AT1 R in AD. We have not observed any significant changes in other RAS components. Our data show that higher AT1 R levels correlate with OS (r=0.301 p=0.01) and β-amyloid load (r=0.245 p=0.04), while higher pERK levels negatively correlate with MN (r=-0.239 p=0.03) and positively correlate with total tangle (r=0.413 p<0.01) and amyloid (r=0.208 p=0.02) scores. Finally, mRNA, protein, and pERK levels of AT1 R were negatively correlated with global cognitive function (GCF) scores (r=-0.216 p=0.05, r=-0.258 p=0.02, r=-0.376 p<0.01, respectively) and were associated with greater decline in GCF (r=0.265 p=0.02, r=0.223 p=0.04, respectively) in all subjects. This study highlights molecular changes in b-RAS and offers insight into the association of these changes with brain pathology in AD. These findings can be important in shedding light on the benefits of RAS-modulating drugs in AD.

Prediction of Decline in Global Cognitive Function Using Machine Learning with Feature Ranking of Gait and Physical Fitness Outcomes in Older Adults.

Gait and physical fitness are related to cognitive function. A decrease in motor function and physical fitness can serve as an indicator of declining global cognitive function in older adults. This study aims to use machine learning (ML) to identify important features of gait and physical fitness to predict a decline in global cognitive function in older adults. A total of three hundred and six participants aged seventy-five years or older were included in the study, and their gait performance at various speeds and physical fitness were evaluated. Eight ML models were applied to data ranked by the p-value (LP) of linear regression and the importance gain (XI) of XGboost. Five optimal features were selected using elastic net on the LP data for men, and twenty optimal features were selected using support vector machine on the XI data for women. Thus, the important features for predicting a potential decline in global cognitive function in older adults were successfully identified herein. The proposed ML approach could inspire future studies on the early detection and prevention of cognitive function decline in older adults.