5-year Cognitive Decline Research Articles

Occupation, Retirement Age, and 20-Year Cognitive Decline: The Atherosclerosis Risk in Communities Neurocognitive Study

Introduction: We examined the association of both midlife occupation and age at retirement with cognitive decline in the Atherosclerosis Risk in Communities (ARIC) biracial community-based cohort. Methods: Current or most recent occupation at ARIC baseline (1987–1989; aged 45–64 years) was categorized based on 1980 US Census major occupation groups and tertiles of the Nam-Powers-Boyd occupational status score (n = 14,090). Retirement status via annual follow-up questionnaires administered ascertained in 1999–2007 was classified as occurring before or after age 70 (n = 7,503). Generalized estimating equation models were used to examine associations of occupation and age at retirement with trajectories of global cognitive factor scores, assessed from visit 2 (1990–1992) to visit 5 (2011–2013). Models were a priori stratified by race and sex and adjusted for demographics and comorbidities. Results: Low occupational status and blue-collar occupations were associated with low baseline cognitive scores in all race-sex strata. Low occupational status and homemaker status were associated with faster decline in white women but slower decline in black women compared to high occupational status. Retirement before age 70 was associated with slower cognitive decline in white men and women and in black men. Results did not change substantially after accounting for attrition. Conclusion: Low occupational status was associated with cognitive decline in women but not in men. Earlier retirement was associated with a slower cognitive decline in white participants and in black men. Further research should explore reasons for the observed associations and race-sex differences.

Midlife sensory and motor functions improve long-term predictions of cognitive decline and incidence of cognitive impairment.

We aimed to assess whether midlife sensory and motor functions improve risk prediction of 10-year cognitive decline and impairment when added to risk prediction models using the Cardiovascular Risk Factors, Aging, and Incidence of Dementia Score (CAIDE) and Framingham Risk Score (FRS). Longitudinal data of N=1529 (mean age 49 years; 54% women) Beaver Dam Offspring Study (BOSS) participants from baseline, 5 and 10-year follow-up were included. We tested whether including baseline sensory (hearing, vision, olfactory) impairment and motor function improves CAIDE or FRS risk predictions of 10-year cognitive decline or cognitive impairment incidence using logistic regressions. Adding sensory and motor measures to CAIDE-only and FRS-only models significantly improved areas under the curve for cognitive decline and impairment models. Including midlife sensory and motor function improved risk predictions of long-term cognitive decline and impairment in middle-aged to older adults. Sensory and motor assessments could contribute to cost-effective and non-invasive screening tools that identify high-risk individuals earlier to target intervention and prevention strategies. Sensory and motor measures improve risk prediction models of cognitive decline.Sensory and motor measures improve risk prediction models of cognitive impairment.Prediction improvements were strongest in midlife (adults<55 years of age).Sensory and motor changes may help identify high-risk individuals early.

3 Olfactory Dysfunction as a Preclinical Biomarker of AD: Psychophysical Olfactory Performance Reflects Hippocampal Integrity in Non-Demented Older Adults

Objective:One of the greatest challenges of the Alzheimer’s disease (AD) epidemic is identifying the disease prior to substantial neurological compromise. The established biomarkers of AD, such as measures of cognitive impairment, hippocampal atrophy, and CSF measures of beta amyloid and tau, used in research and drug trials are less indicative of AD pathology in preclinical, non-demented, populations. Olfactory dysfunction, a well-established sensory impairment of AD found to correlate strongly with tau burden and hippocampal volume measures, has shown to be a promising preclinical biomarker for AD progression. Several studies have found either impaired odor identification or odor memory at baseline to predict 5-year follow-up cognitive decline and conversion from MCI to AD, but less is known about how olfactory performance reflects the integrity of associated brain regions such as the hippocampus. The present analysis aims to explore the value of psychophysical olfactory assessment as biomarker measure in preclinical AD studies and drug trials by investigating its relationships with structural measures of the hippocampus.Participants and Methods:A sample consisted of non-demented older adults (age &gt;75), recruited from the UCSD Alzheimer’s Disease Research Center as part of a ongoing olfactory biomarker study. Participants completed the AD Assessment Scale-Cognitive Subscale-13 (ADAS-Cog-13), San Diego Odor Identification Test (SDOIT), tests of odor recognition memory (ORMem) and odor associative memory (OAM), and MRI derived hippocampal volumes and average hippocampal occupancy (Avg HOC). Left and right hippocampal volumes were adjusted for each participant’s estimated intracranial volume. Bivariate correlations were calculated for ADAS-Cog-13 and SDOIT total scores, performance scores for odor recognition and odor associative memory tests, and the three hippocampal measures (bilateral volumes and average occupancy).Results:ADAS-Cog-13 score did not show significant correlations with either hippocampal measure at the .05 level. SDOIT scores were significantly correlated with the measure of Avg HOC (p&lt;.05). ORMem false positive responses were significantly correlated with Avg HOC (p&lt;.01) and right hippocampal volume (p&lt;.05). ORMem miss responses and OAM errors were both correlated with left (p&lt;.05) and right (p&lt;.01) hippocampal volumes.Conclusions:These results demonstrate that psychophysical assessments of odor identification and odor memory can better reflect the integrity of the hippocampus in nondemented older adults, compared to the neuropsychological ADAS-Cog-13. This is congruent with olfactory dysfunction preceding cognitive-memory decline in AD cases and provides support for the utility of psychophysical olfactory assessment along with other established AD biomarkers in research and drug trials in preclinical populations.Acknowledgements:Supported by NIH grant # R01AG062006-04 from the National Institute on Aging to CM. Special thank you to the staff and participants of the UCSD ADRC, especially Christina Gigliotti, and Aaron Jacobson at the UCSD Center for fMRI.

Midlife Hemostasis Measures, 20-Year Cognitive Decline, and Incident Dementia.

Blood concentrations of hemostatic factors affect thrombosis and bleeding diathesis and may contribute to cognitive impairment through modifiable vascular pathologies. Whether hemostasis, assessed in middle age, is associated with late-life cognitive impairment remains largely unknown in a community-dwelling population. Using data from 14,128 participants with cognitive function measurements in 1990-1992 from the Atherosclerosis Risk in Communities study, we assessed the associations of hemostasis measures with 20-year changes in cognitive performance and incident dementia. Activated partial thromboplastin time (aPTT) and level of fibrinogen, von Willebrand factor (VWF), factor VIII, factor VII, factor XI, d-dimer, and soluble thrombomodulin were measured in 1987-1989 or 1993-1995. Hemostasis measures were categorized into quintiles, with the lowest quintile indicating low coagulability. Cognitive performance was characterized using a combined z-score from 3 tests (that is, delayed word recall test [DWRT], digit symbol substitution [DSST], and word fluency test [WFT]), assessed in 1990-1992, 1996-1998, and 2011-2013. Dementia was determined either from in-person evaluations or using dementia surveillance through 2017. Mixed-effects models and Cox proportional hazards models were used to assess cognitive trajectories and risk of dementia, respectively. Among 12,765 participants with hemostasis measures in 1987-1989, who were aged 47-70 years at the first cognitive assessment, we observed significant trends of shorter aPTT (p for trend <0.001; difference in 20-year cognitive decline for fifth vs first quintile [Q5 vs Q1]: -0.104 [95% CI -0.160 to -0.048]) and higher levels of factor VII (p < 0.002; Q5 vs Q1: -0.085 [-0.142, -0.028]) and factor VIII (p = 0.033; Q4 vs Q1: -0.055 [-0.111, -0.000]) with greater 20-year cognitive declines. The associations with the decline in DSST were stronger than those with the decline in WFT or DWRT. Consistently, shorter aPTT and higher factor VIII levels were associated with higher dementia risk with HRs for Q5 vs Q1 of 1.23 (95% CI 1.07 to 1.42) and 1.17 (1.01-1.36), respectively, and p for trend of 0.008 and 0.024, respectively. Overall, our study found consistent trend associations of aPTT and factor VIII measured in midlife with cognitive decline and incident dementia over 20 years, likely driven by vascular pathologies.

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.

PS-BPP04-3: ASSOCIATION BETWEEN URINARY NA/K RATIO AND CHANGES IN COGNITIVE FUNCTION AND ALBUMINURIA OVER 10 YEARS IN A GENERAL POPULATION

Objective: Preservation of cognitive function is an important issue in extending healthy life expectancy in an aging society. To elucidate factors associated with changes in cognitive function over a 10-year period in a general population. Design and method: A total of 984 subjects (381 males, 603 females, mean age 62.4 years) underwent a physical examination, blood test, urinalysis and the mini-mental state examination as an evaluation of cognitive function in 2009 and 2018. After excluding subjects with diabetes at baseline, the remaining subjects were followed-up 10 years later. Complete data sets were available from 890 subjects (330 males, 560 females, mean age 62.4 years) for prospective analysis. Logistic regression was performed to determine factors associated with changes in cognitive function and albuminuria after 10 years. Results: The logistic regression analysis revealed that the age (OR 1.11; 95%C.I: 1.08–1.14, p &lt; 0.0001), sex (male, OR 0.59; 95%C.I: 0.38–0.91,P &lt; 0.05), HbA1c (OR 2.18; 95%C.I: 1.13–4.23, P &lt; 0.05), hs-CRP (OR 1.22; 95%C.I: 1.03–1.46, P &lt; 0.05), and albuminuria(OR 1.48; 95%C.I: 1.19–1.83, p &lt; 0.001) were associated with cognitive decline over 10 years. The age (OR 1.11; 95% C.I: 1.08–1.14, p &lt; 0.0001) and albuminuria (OR 1.26; 95%C.I: 1.01–1.59, p &lt; 0.05) were independently correlated to cognitive decline in stepwise logistic regression analysis. Furthermore, the age (OR 1.01; 95%C.I: 1.05–1.12, p &lt; 0.0001), uric acid (OR 1.36; 95%C.I: 1.15–1.62, p &lt; 0.001), insulin (OR 1.48; 95%C.I: 1.01–2.04, p &lt; 0.05) and urinary Na/K ratio (OR 1.14; 95%C.I: 1.05–1.25, p &lt; 0.01) were independently related to the progression of albuminuria over 10 years in stepwise logistic regression analysis. Conclusions: Urinary albuminuria and age were independently associated with 10-year cognitive decline, and urinary Na/K ratio was independently associated with progression of urinary albuminuria. The urinary Na/K ratio may have important significance in cognitive decline.

Inflammation, metabolic dysregulation and environmental neurotoxins and risk of cognitive decline and impairment in midlife.

Age-related declines in cognitive function may begin in midlife. To determine whether blood-based biomarkers of inflammation, metabolic dysregulation and neurotoxins are associated with risk of cognitive decline and impairment. Baseline blood samples from the longitudinal Beaver Dam Offspring Study (2005-2008) were assayed for markers of inflammation, metabolic dysregulation, and environmental neurotoxins. Cognitive function was measured at baseline, 5-year (2010-2013) and 10-year (2015-2017) examinations. Participants without cognitive impairment at baseline and with cognitive data from at least one follow-up were included. Cox proportional hazards models were used to evaluate associations between baseline blood biomarkers and the 10-year cumulative incidence of cognitive impairment. Poisson models were used to estimate the relative risk (RR) of 5-year decline in cognitive function by baseline blood biomarkers. Models were adjusted for age, sex, education, and cardiovascular related risk factors. Participants (N = 2421) were a mean age of 49years and 55% were women. Soluble vascular cell adhesion molecule-1 (sVCAM-1Tertile(T)3 vs T1-2 hazard ratio (HR) = 1.72, 95% confidence interval (CI) = 1.05,2.82) and hemoglobin A1C (HR = 1.75, 95% CI = 1.18,2.59, per 1% in women) were associated with the 10-year cumulative incidence of cognitive impairment. sVCAM-1 (RRT3 vs T1-2 = 1.45, 95% CI = 1.06,1.99) and white blood cell count (RR = 1.10, 95% CI = 1.02,1.19, per 103/μL) were associated with 5-year cognitive decline. Biomarkers related to inflammation and metabolic dysregulation were associated with an increased risk of developing cognitive decline and impairment. These results extend previous research in cognitive aging to early markers of cognitive decline in midlife, a time when intervention methods may be more efficacious.

Free-living wrist and hip accelerometry forecast cognitive decline among older adults without dementia over 1- or 5-years in two distinct observational cohorts

The prevalence of major neurocognitive disorders is expected to rise over the next 3 decades as the number of adults ≥65 years old increases. Noninvasive screening capable of flagging individuals most at risk of subsequent cognitive decline could trigger closer monitoring and preventive strategies. In this study, we used free-living accelerometry data to forecast cognitive decline within 1- or 5-years in older adults without dementia using two cohorts. The first cohort, recruited in the south side of Chicago, wore hip accelerometers for 7 continuous days. The second cohort, nationally recruited, wore wrist accelerometers continuously for 72 h. Separate classifier models forecasted 1-year cognitive decline with over 85% accuracy using hip data and forecasted 5-year cognitive decline with nearly 70% accuracy using wrist data, significant improvements compared to demographics and comorbidities alone. The proposed models are readily translatable to clinical practices serving ageing populations.

Brain Imaging Features Associated with 20-Year Cognitive Decline in a Community-Based Multiethnic Cohort without Dementia

Introduction: This study aimed to characterize the association of cognitive decline starting in midlife with brain pathology in late life in the absence of dementia. Methods: Nondemented Atherosclerosis Risk in Communities participants with brain imaging, all cognitive factor scores (CFSs), and nonmissing covariates were included. CFSs were collected at three visits across 21 years (1990–2013) (short-term cognitive change [1990–1996], long-term cognitive change [1990–2013]), and brain magnetic resonance imaging and florbetapir positron emission tomography (PET) imaging were collected in 2011–13 (PET subset n = 327). Outcomes of interest were total and regional brain volumes (cm³), log₂ (white matter hyperintensity volume), white matter integrity (fractional anisotropy, mean diffusivity), ≥1 lacunar infarct (3–20 mm), and elevated brain β-amyloid (SUVR >1.2). Multivariable linear/logistic regression related outcomes to CFS slopes after adjusting for demographics and total intracranial volume. Results: At baseline, the 1,734 participants had a mean (SD) age of 55 (5.2) years, and were 60% female and 26% Black. After adjustment, a 1-SD larger long-term decline in CFS was associated with a smaller relative total brain volume by 1.2% (95% CI: 1.0, 1.5), a smaller relative temporal lobe meta region volume by 1.9% (1.5, 2.3), a 13% (9, 17) larger volume of white matter hyperintensities, a 1.3-fold (1.2, 1.4) higher odds of having ≥1 lacune, and 1.7-fold (1.3, 2.2) higher odds of elevated brain β-amyloid deposition and worse white matter integrity. Some long-term associations were also found for midlife short-term declines in CFS. Conclusions: This study provides evidence that starting in midlife, short-term and long-term declines in cognition are associated with multiple deleterious late-life differences in nondemented brains.

The Associations of Dietary Copper With Cognitive Outcomes.

Dietary copper intake may be associated with cognitive decline and dementia. We used data from 10,269 participants of the Atherosclerosis Risks in Communities Study to study the associations of dietary copper intake with 20-year cognitive decline and incident dementia. Dietary copper intake from food and supplements was quantified using food frequency questionnaires. Cognition was assessed using 3 cognitive tests at study visits; dementia was ascertained at study visits and via surveillance. Multiple imputation by chained equations was applied to account for the missing information of cognitive function during follow-up. Survival analysis with parametric models and mixed-effect models were used to estimate the associations for incident dementia and cognitive decline, respectively. During 20 years of follow-up (1996-1998 to 2016-2017), 1,862 incident cases of dementia occurred. Higher intake of dietary copper from food was associated with higher risk of incident dementia among those with high intake of saturated fat (hazard ratio = 1.49, 95% confidence interval: 1.04, 1.95). Higher intake of dietary copper from food was associated with greater decline in language overall (beta = -0.12, 95% confidence interval: -0.23, -0.02). Therefore, a diet high in copper, particularly when combined with a diet high in saturated fat, may increase the risk of cognitive impairment.

Non-alcoholic fatty liver disease and cognitive function in middle-aged adults: the CARDIA study

BackgroundNon-alcoholic fatty liver disease (NAFLD) is associated with cardiovascular disease (CVD) risk factors that have been linked to cognitive decline. Whether NAFLD is associated with cognitive performance in midlife remains uncertain.MethodsCoronary Artery Risk Development in Young Adults study participants with CT examination and cognitive assessment at Y25 (2010–2011; n = 2809) were included. Cognitive function was reassessed at Y30. NAFLD was defined according to liver attenuation and treated both continuously and categorically (using ≤ 40 and ≤ 51 Hounsfield units to define severity) after exclusion for other causes of liver fat. Cognitive tests including the Digit Symbol Substitution (processing speed), Rey Auditory Verbal Learning (verbal memory), and Stroop (executive function) were analyzed with standardized z-scores. Linear models were constructed to (a) examine the cross-sectional associations of NAFLD with cognitive scores and (b) evaluate its predictive role in 5-year change in cognitive performance.ResultsParticipants’ mean age (Y25) was 50.1 (SD 3.6) years (57% female; 48% black), with 392 (14%) having mild NAFLD and 281 (10%) having severe NAFLD. NAFLD was positively associated with CVD risk factors and inversely associated with cognitive scores. However, after adjustment for CVD risk factors, no associations were shown between NAFLD and cognitive scores (all βs ≈ 0). Similarly, no associations were observed with 5-year cognitive decline. CVD history, hypertension, smoking, diabetes and hypertriglyceridemia showed stronger associations with baseline cognitive scores and were predictive of subsequent cognitive decline (all P ≤ .05).ConclusionAmong middle-aged adults, inverse associations between NAFLD and cognitive scores were attenuated after adjustment for CVD risk factors, with the latter predictive of poorer cognitive performance both at baseline and follow-up.

The Utility of Assessing Health-Related Quality of Life to Predict Cognitive Decline and Dementia.

Health-related quality of life (HRQoL) has been shown to predict adverse health outcome in the general population. We examined the cross-sectional association between HRQoL and cognitive performance at baseline. Next, we explored whether baseline HRQoL predicted 5-year incident cognitive decline and dementia and whether there were gender differences. 19,106 community-dwelling participants from the ASPirin in Reducing Events in the Elderly (ASPREE) trial, aged 65-98 years, free of major cognitive impairments, and completed the HRQoL 12-item short-form (SF-12) at baseline (2010-2014), were followed until June 2017. The physical (PCS) and mental component scores (MCS) of SF-12 were calculated. The cognitive tests were assessed at baseline, year 1, 3, 5, and 7 or close-out visit. Cognitive decline was defined as > 1.5 SD drop from baseline on any of the cognitive tests. Dementia was adjudicated according to DSM-IV criteria. Linear and Cox proportional-hazards regressions were used to examine the cross-sectional and longitudinal associations respectively. At baseline, higher PCS and MCS were associated with better cognition. Over a median 4.7-year follow-up, higher MCS was associated with a reduced risk of cognitive decline and dementia (12% and 15% respectively, per 10-unit increase) and a 10-unit higher PCS was associated with a 6% decreased risk of cognitive decline. PCS did not predict dementia incidence. Findings were not different by gender. Our study found that higher HRQoL, in particular MCS, predicted a reduced risk of cognitive decline and dementia over time in community-dwelling older people.

Sex-specific associations between lipids and cognitive decline in the middle-aged and elderly: a cohort study of Chinese adults

BackgroundStudies regarding the lipid-cognition relationship have increasingly gained popularity but have generated much mixed results. To date, few studies have focused on the difference between sexes.MethodsThis study included 6792 Chinese adults aged over 45 years (women, 48.56%; mean age, 57.28 years), who were free of severe conditions known to affect cognitive function at the baseline (2011). Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-c), low-density lipoprotein cholesterol (LDL-c), and triglycerides (TG) were assessed at baseline, and both continuous and categorical values were used in final analyses. Global cognitive functions were assessed by the word recall test and the mental status test in 2011, 2013, and 2015, respectively. We graded participants into three groups according to the cognitive change slopes: no decline (≥ 0), moderate decline (median to 0), and severe decline (< median). Sex-specific associations between blood lipids and cognitive decline were analyzed using ordinal logistic models, adjusting for sociodemographic information, lifestyle behaviors, and health status.ResultsHigher baseline TC and LDL-C concentrations exhibited no significant association with 5-year cognitive decline in men but were significantly associated with greater 5-year cognitive decline in women [odds ratio (OR) 1.026, 95% confidence interval (CI) 1.003, 1.050; OR 1.026, CI 1.002, 1.051, respectively]. For higher serum HDL-c levels, a significantly protective effect on cognition was observed in men, but a slightly adverse effect was found in women (not significant after Bonferroni correction). TG presented almost no effect on later cognition in either sex.ConclusionDifferent associations between sexes were observed for the lipid-cognition relationship, and maintaining serum cholesterol levels at an appropriate range may have a positive effect on cognitive health.

Abstract P402: Aortic Stiffness and 5-year Cognitive Decline Among Community-dwelling Older Adults: The Atherosclerosis Risk in Communities Neurocognitive Study (aric-ncs)

Background: Vascular aging is associated with cognitive decline. Aortic stiffness is a hallmark of vascular aging. We tested the hypothesis that greater aortic stiffness is associated with a faster rate of cognitive decline over 5 years among older adults. Methods: A prospective cohort study at the 5th (2011-2013) and 6th (2016-2017) examinations of the Atherosclerosis Risk in Communities Neurocognitive Study (ARIC-NCS) was conducted to quantify the association between baseline aortic stiffness and cognitive decline over 5 years. A total of 4639 participants (mean age: 75 years, 41% men, 22% Black) with baseline measures of aortic stiffness and cognitive function were included in the analysis. Aortic stiffness was measured as carotid-femoral pulse wave velocity (cfPWV) using the Omron VP-1000 Plus device and analyzed continuously per 1 standard deviation meter/second (3.20 m/s). Elevated aortic stiffness was defined as the upper 25th percentile of cfPWV (13.39 m/s). Cognitive function was based on ten neuropsychological tests across multiple domains of cognition, including memory, executive function/processing speed, and language. A global cognitive performance factor score was estimated based on all cognitive tests at both visits. Multivariable linear regression was used to examine the associations of each standard deviation (SD) increment in cfPWV and elevated cfPWV with annual cognitive decline over 5 years. Interactions with baseline cognitive status were assessed. To account for attrition (35% over 5 years), multiple imputation by chained equations was used to impute missing global cognitive performance factor scores at visit 6. Results: Each 1 SD increase in cfPWV was associated with 0.008 SD (Beta (β)=-0.008, 95% confidence interval (CI): -0.010, -0.003) annual rate of decline in cognitive function after adjustment for age, sex, education, race-center and ApoE4. With additional adjustment for ever smoking, total weekly physical activity time, mean arterial pressure, diabetes, and body mass index, each SD higher cfPWV was associated with 0.005 SD (β=-0.005, 95% CI: -0.010, -0.001) annual rate of decline in cognitive function. Elevated cfPWV was associated with 0.015 SD (β=-0.015, 95% CI: -0.024, -0.005) annual decline in cognitive function, and with 0.010 SD (β=-0.010, 95% CI: -0.020, 0.0001) annual decline after additional adjustment. Conclusion: Higher aortic stiffness is associated with the rate of decline in global cognitive function among community-dwelling older adults. The hemodynamic sequelae of aortic stiffening may contribute to cognitive decline among older adults.

Midlife Smaller and Larger Infarctions, White Matter Hyperintensities, and 20-Year Cognitive Decline: A Cohort Study.

Smaller (<3-mm) infarctions are associated with stroke and stroke mortality, but relationships with cognitive decline are unknown. To characterize the relationships of smaller, larger, and both smaller and larger infarctions in middle age with 20-year cognitive decline. Longitudinal cohort study. Two ARIC (Atherosclerosis Risk in Communities) study sites with magnetic resonance imaging data (1993 to 1995) and up to 5 cognitive assessments over 20 years. Stroke-free participants aged 50 years or older. Infarctions were categorized as none, smaller only, larger only (3 to 20 mm), or both smaller and larger. Global cognitive Z scores were derived from 3 cognitive tests administered up to 5 times. Mixed-effects models estimated adjusted associations between infarctions and cognitive decline. Results are the average difference in standardized cognitive decline associated with infarctions versus no infarctions. Among 1884 participants (mean age, 62 years; 60% women; 50% black), 1611 (86%) had no infarctions, 50 (3%) had smaller infarctions only, 185 (10%) had larger infarctions only, and 35 (2%) had both. Participants with both smaller and larger infarctions had steeper cognitive decline by more than half an SD (difference, -0.57 SD [95% CI, -0.89 to -0.26 SD]) compared with those who had no infarctions. Amounts of cognitive decline associated with only smaller infarctions and only larger infarctions were similar and were not statistically different from that associated with no infarctions. Few participants had only smaller infarctions or both smaller and larger infarctions, and the data lacked counts of smaller infarctions and volumes of white matter hyperintensities. The substantial cognitive decline from middle age associated with having both smaller and larger infarctions, but not larger infarctions alone, suggests that the combination of smaller and larger infarctions may escalate risk for cognitive decline later in life in stroke-free persons. National Institutes of Health.

Neuroprotective Biomarkers and Cognitive Function in a Long-Term Prospective Population-based Study of Aging US Adults.

Relationships between brain-derived neurotrophic factor (BDNF), insulin-like growth factor (IGF-1), aldosterone, and cognition in aging were evaluated in the population-based Epidemiology of Hearing Loss Study (1993 to present). Beginning in 1998 to 2000, cognitive impairment was assessed by report of physician diagnoses and the Mini-Mental State Examination. In 2009 to 2010 and 2013 to 2016, information was collected on diagnosis of mild cognitive impairment/dementia. Decline in cognitive function was assessed by principal component analysis from additional tests administered during 2009 to 2010 and 2013 to 2016. BDNF, IGF-1, and aldosterone were measured in serum collected in 1998 to 2000. There were 1970 participants (mean age=66.9 y; 59.1% female) without cognitive impairment at baseline. Among women, low BDNF was associated with 16-year incident cognitive impairment [hazard ratio=1.76; 95% confidence interval (CI)=1.04, 2.98]. Among men, increasing IGF-1 was associated with decreased risk [per SD: relative risk (RR)=0.57; 95% CI=0.35, 0.92], whereas increasing aldosterone levels were associated with increased risk (per SD: RR=1.28; 95% CI=1.01, 1.62) for 5-year incident mild cognitive impairment/dementia. Overall, low BDNF was associated with increased risk (RR=1.52; 95% CI=1.02, 2.26) for 5-year cognitive decline. Low levels of serum BDNF and IGF-1 were associated with poorer cognition during aging. There may be differential biomarker effects by sex.

Role of gait speed and grip strength in predicting 10-year cognitive decline among community-dwelling older people

BackgroundThe gait speed and handgrip strength represented the core determinants of physical frailty and sarcopenia, which were reported to be associated with cognitive impairment and decline. Different physical measures might differentially affect cognitive changes, such as higher-level cognitive change and global cognitive decline. This study examined the differential associations of gait speed and handgrip strength with 10-year cognitive changes among community-dwelling older people.MethodsParticipants aged 60 years and over living in the community were invited for study. Gait speed and handgrip strength were classified into 5 groups based on quintiles at baseline. Cognitive functions were assessed using the Mini-Mental State Examination (MMSE) and Digit Symbol Substitution Test (DSST) every 2 years from baseline for a period of 10 years. Linear mixed effects models were used to determine the role of gait speed and handgrip strength in the prediction of 10-year cognitive changes by adjusting covariates, including age, gender, education, depressive symptoms, marital status, smoking status, instrumental activities of daily life (IADL), Charlson Comorbidity Index (CCI), and body mass index (BMI) at baseline.ResultsA total of 1096 participants were enrolled in the study. The mean age was 69.4 ± 5.8 years and 50.9% were male. The slowest gait speed group showed a significantly greater decline in the DSST scores over 10 years than the highest group (estimate = 0.28 and P = 0.003), but not in the MMSE scores (estimate = 0.05 and P = 0.078). The lowest handgrip strength group showed a significantly greater decline in the MMSE scores than the highest group (estimate = 0.06 and P = 0.039) and in the DSST scores than the highest two quintiles (estimate = 0.20 and P = 0.033 for the fourth quintile; estimate = 0.20 and P = 0.040 for the highest quintile) over 10-year follow-up.ConclusionsA slow gait speed could predict 10-year cognitive decline using DSST, and a low handgrip strength could predict 10-year cognitive decline using MMSE in addition to DSST. Thus both physical measures are lined to cognitive decline but there may be different mechanisms between brain and physical functions.

Midlife adiposity predicts cognitive decline in the prospective Multicenter AIDS Cohort Study.

Obesity is a common, modifiable cardiovascular and cerebrovascular risk factor. Among people with HIV, obesity may contribute to multisystem dysregulation including cognitive impairment. We examined body mass index (BMI) and central obesity (waist circumference [WC]) in association with domain-specific cognitive function and 10-year cognitive decline in men with HIV infection (MWH) vs HIV-uninfected (HIV-) men. A total of 316 MWH and 656 HIV- Multicenter AIDS Cohort Study participants ≥40 years at baseline, with neuropsychological testing every 2 years and concurrent BMI and WC measurements, were included. MWH were included if taking ≥2 antiretroviral agents and had HIV-1 RNA <400 copies/mL at >80% of visits. Mixed-effects models included all visits from 1996 to 2015, stratified by HIV serostatus, and adjusted for sociodemographic, behavioral, and clinical characteristics. At baseline and follow-up, 8% of MWH and 15% of HIV- men and 41% of MWH and 56% of HIV- men were ≥60 years, respectively. Cross-sectionally, higher BMI was inversely associated with motor function in MWH and HIV- men, and attention/working memory in HIV- men. WC was inversely associated with motor function in MWH and HIV- men. Longitudinal associations indicated an obese BMI was associated with a less steep decline in motor function in MWH whereas in HIV- men, obesity was associated with a greater decline in motor function, learning, and memory. WC, or central obesity, showed similar patterns of associations. Higher adiposity is associated with lower cognition cross-sectionally and greater cognitive decline, particularly in HIV- men. Overweight and obesity may be important predictors of neurologic outcomes and avenues for prevention and intervention.

Associations of Sleep Characteristics With Cognitive Function and Decline Among Older Adults.

Sleep laboratory studies find that restricted sleep duration leads to worse short-term cognition, especially memory. Observational studies find associations between self-reported sleep duration or quality and cognitive function. However self-reported sleep characteristics might not be highly accurate, and misreporting could relate to cognition. In the Sleep Study of the National Social Life, Health, and Aging Project (NSHAP), a nationally representative cohort of older US adults (2010-2015), we examined whether self-reported and actigraph-measured sleep are associated with cross-sectional cognitive function and 5-year cognitive decline. Cognition was measured with the survey adaptation of the multidimensional Montreal Cognitive Assessment (MoCA-SA). At baseline (n = 759), average MoCA-SA score was 14.1 (standard deviation, 3.6) points of a possible 20. In cross-sectional models, actigraphic sleep-disruption measures (wake after sleep onset, fragmentation, percentage sleep, and wake bouts) were associated with worse cognition. Sleep disruption measures were standardized, and estimates of association were similar (range, -0.37 to -0.59 MoCA-SA point per standard deviation of disruption). Actigraphic sleep-disruption measures were also associated with odds of 5-year cognitive decline (4 or more points), with wake after sleep onset having the strongest association (odds ratio = 1.43, 95% confidence interval: 1.04, 1.98). Longitudinal associations were generally stronger for men than for women. Self-reported sleep showed little association with cognitive function.

Systemic inflammation during midlife and cognitive change over 20 years: The ARIC Study.

To examine the association between systemic inflammation measured during midlife and 20-year cognitive decline. Within the Atherosclerosis Risk in Communities cohort study, inflammatory biomarkers were measured during middle adulthood. We created an inflammation composite score using 4 blood biomarkers measured at visit 1 (fibrinogen, white blood cell count, von Willebrand factor, and factor VIII); we measured C-reactive protein (CRP) at visit 2. Cognition was assessed over 3 visits spanning 20 years using measures of memory, executive function, and language. A total of 12,336 participants (baseline age 56.8 [5.7], 21% black, 56% women) were included. After adjusting for demographic variables, vascular risk factors, and comorbidities, each standard deviation (SD) increase in midlife inflammation composite score was associated with an additional 20-year decline of -0.035 SD (95% confidence interval: -0.062 to -0.007) on the cognitive composite score. We found a similar association between each SD increase in midlife CRP level and additional 20-year cognitive decline (-0.038 SD, 95% confidence interval: -0.057 to -0.019). Participants with a midlife inflammation composite score in the top quartile had a 7.8% steeper cognitive decline, compared to participants in the lowest quartile; CRP in the top quartile was associated with an 11.6% steeper cognitive decline. In cognitive domain-specific analyses, elevated midlife inflammatory markers were most consistently associated with declines in memory. Results were similar after adjusting for attrition using inverse probability weighting. Our findings highlight what may be an early pathogenic role for systemic inflammation as a driver of cognitive decline in the decades leading up to older adulthood.