Risk Of Incident Cognitive Impairment Research Articles

Developing Integer‐based Risk Scores for Predicting the Risk of Incident Cognitive Impairment in Cognitively Normal Older Adults

AbstractBackgroundWe aimed to developed integer‐based risk scores for predicting incident cognitive impairment up to 10 years in initially cognitively normal older adults.MethodsParticipants were 479 older adults (aged 60 to 90) from longitudinal studies of aging and Alzheimer’s disease from the Knight ADRC at Washington University in St. Louis. The primary outcome was incident cognitive impairment, defined as conversion from Clinical Dementia Rating (CDR®) 0 to >0. The sample was divided into training (60%) and test (40%) sets. Feature‐sets were formed from combinations of four categories of variables: demographics (D), genetics (G), cognitive measures (C), and biomarkers (B) (Details in Figure 1 legend). Utilizing a modified version of the AutoScore‐Survival algorithm, variables were ranked based on variable importance using reduction in predictive accuracy due to replacement with a random permutation value in combination with Random Survival Forests. Variables were iteratively included in constructing risk score models based on coefficients of Cox regression models.ResultsFive risk score models were developed using five feature‐sets. All models retained age, APOE4 status, free recall from the Free and Cued Selective Reminding Test, hippocampal atrophy, and Tau positivity when included as potential variables in the feature‐sets. The risk score derived from the DGCB model had a Harrell’s concordance index (C‐index) of 0.754 and integrated Area Under the ROC Curve (iAUC) of 0.792. The best performing model without biomarkers used the DGC feature‐set and had a C‐index of 0.694 and iAUC of 0.699 while the risk score using the DG feature‐set only had a C‐index of 0.632 and iAUC of 0.647. Participants who had risk scores in the top quartile of the DGCB model risk score had an increased rate of conversion to CDR > 0.ConclusionsWe developed five risk score models for predicting incident cognitive impairment. Risk scores consisted of different sets of measures which differed in ease‐of‐access and costs. Using such simple risk scores that do not include biomakers as clinical decision support tools is practical in the clinical setting. Including biomarkers in risk scores provides slight improvement to classification accuracy, emphasizing their importance in research settings.

Antiplatelet therapy and incident cognitive impairment or dementia-a systematic review and meta-analysis of randomised clinical trials.

The benefit of antiplatelet therapy in preventing cognitive impairment or dementia is uncertain. We investigated the association between antiplatelet therapy and incident cognitive impairment or dementia in randomised clinical trials. We searched PubMed, EMBASE and CENTRAL for randomised clinical trials published from database inception through 1 February 2023. Trials that evaluated the association of antiplatelet therapy with incident cognitive impairment or dementia were included. For single-agent antiplatelet, the control group was placebo. For dual agent antiplatelet therapy, the control group was single-agent monotherapy. A random-effects meta-analysis model was used to report pooled treatment effects and 95% confidence intervals (CIs). The primary outcome was incident cognitive impairment or dementia. Secondary outcomes included change in cognitive test scores. A total of 11 randomised clinical trials were included (109,860 participants). All reported the incidence of cognitive impairment or dementia on follow-up. The mean (SD) age of trial participants was 66.2 (7.9) years. Antiplatelet therapy was not significantly associated with a reduced risk of cognitive impairment or dementia (11 trials; 109,860 participants) (3.49% versus 4.18% of patients over a mean trial follow-up of 5.8years; odds ratio [OR], 0.94 [95% CI, 0.88-1.00]; absolute risk reduction, 0.2% [95% CI, -0.4% to 0.009%]; I2 = 0.0%). Antiplatelet therapy was not significantly associated with mean change in cognitive test scores. In this meta-analysis, antiplatelet therapy was not significantly associated with a lower risk of incident cognitive impairment or dementia, but the CIs around this outcome do not exclude a modest preventative effect.

105 Antiplatelet therapy and incident cognitive impairment or dementia—a systematic review and Meta-analysis of randomised clinical trials.

Abstract Background The benefit of antiplatelet therapy in the prevention of cognitive impairment or dementia is uncertain. We investigated the association between antiplatelet therapy with incident cognitive impairment or dementia in randomised clinical trials. Methods We searched PubMed, EMBASE, and CENTRAL for randomised clinical trials published from database inception through Feb 1st, 2023. Trials that evaluated the association of antiplatelet therapy with incident cognitive impairment or dementia were included. For single agent antiplatelet, the control group was placebo and for dual agent antiplatelet therapy, the control group was single agent monotherapy. Two authors screened and independently extracted all data, and a random-effects meta-analysis model was used to report pooled treatment effects and 95% Confidence Intervals. The primary outcome was incident cognitive impairment or dementia. Secondary outcomes included change in cognitive test scores. Results Eleven randomised clinical trials were eligible for inclusion (109,860 participants), all of which reported the incidence of cognitive impairment or dementia on follow-up. The mean (SD) age of trial participants was 66.2 (7.9) years and 46,150 (42%) were women. The mean duration of follow-up was 70 months. Antiplatelet therapy, compared to control, was not significantly associated with a reduced risk of cognitive impairment or dementia (11 trials; 109,860 participants) (3.49% vs 4.18% of patients over a mean trial follow-up of 5.8 years; odds ratio [OR], 0.94 [95% CI, 0.88–1.00]; absolute risk reduction, 0.2% [95% CI, −0.4% to 0.009%]; I2 = 0.0%). Antiplatelet therapy was not significantly associated with mean change in cognitive test scores. Conclusion In this meta-analysis of randomised clinical trials, antiplatelet therapy was not significantly associated with a lower risk of incident cognitive impairment or dementia. The confidence intervals around this outcome do not exclude a modest preventative effect, and at a population level this could have a substantial benefit. Further large trials with longer term follow up are needed.

Lean-to-fat tissue ratio as a risk factor for cognitive impairment in patients undergoing maintenance hemodialysis

ObjectiveThe relationship between body mass index (BMI) and cognitive impairment (CI) remains controversial, and no research has been done to explore the effect of lean-to-fat (L/F) tissue ratio on the risk of CI in patients undergoing maintenance hemodialysis (MHD) so far. This study aimed to explore the effect of L/F tissue ratio on the risk of incident CI in patients undergoing MHD. MethodsIn this observational cohort study, 3356 patients were recruited and followed up for a median of 2 years. Global cognitive function was measured using Mini-Mental State Examination score. Lean tissue mass (LTM) and fat tissue mass (FTM) were analyzed using body composition monitor based on bioimpedance spectroscopy (BCM-BIS), and L/F tissue ratio was calculated by LTM divided by FTM. Hazard ratios (HRs) for incident CI were determined by Cox regression. ResultsThe median age of the cohort was 55 years, and 68.7% patients were less educated. During the follow-up period, 1249 patients (37.2%) experienced incident CI. Patients with lower L/F tissue ratios had significantly higher risks of CI (HR 1.51, 95% confidence interval 1.24–1.84; p < 0.001) than those with higher L/F tissue ratios. The association between L/F tissue ratio and incident CI persisted in all subgroups stratified by sex, age, education status, especially in older and less educated participants. Both in all our patients and subgroups, BMI and CI occurrence were not independently relevant. ConclusionThe L/F tissue ratio rather than BMI was an independent risk factor of incident cognitive impairment in patients undergoing MHD.

Blood Pressure, Incident Cognitive Impairment, and Severity of CKD: Findings From the Chronic Renal Insufficiency Cohort (CRIC) Study

Hypertension is a known risk factor for dementia and cognitive impairment. There are limited data on the relation of systolic blood pressure (SBP) and diastolic blood pressure (DBP) with incident cognitive impairment in adults with chronic kidney disease. We sought to identify and characterize the relationship among blood pressure, cognitive impairment, and severity of decreased kidney function in adults with chronic kidney disease. Longitudinal cohort study. 3,768 participants in the Chronic Renal Insufficiency Cohort (CRIC) Study. Baseline SBP and DBP were examined as exposure variables, using continuous (linear, per 10-mm Hg higher), categorical (SBP<120 [reference], 120 to 140,>140mm Hg; DBP<70 (reference), 70 to 80, > 80mm Hg) and nonlinear terms (splines). Incident cognitive impairment defined as a decline in Modified Mini-Mental State Examination (3MS) score to greater than 1 standard deviation below the cohort mean. Cox proportional hazard models adjusted for demographics as well as kidney disease and cardiovascular disease risk factors. The mean age of participants was 58±11 (SD) years, estimated glomerular filtration rate (eGFR) was 44mL/min/1.73m2 ± 15 (SD), and the median follow-up time was 11 (IQR, 7-13) years. In 3,048 participants without cognitive impairment at baseline and with at least 1 follow-up 3MS test, a higher baseline SBP was significantly associated with incident cognitive impairment only in the eGFR>45mL/min/1.73m2 subgroup (adjusted hazard ratio [AHR], 1.13 [95% CI, 1.05-1.22] per 10mm Hg higher SBP]. Spline analyses, aimed at exploring nonlinearity, showed that the relationship between baseline SBP and incident cognitive impairment was J-shaped and significant only in the eGFR>45mL/min/1.73m2 subgroup (P=0.02). Baseline DBP was not associated with incident cognitive impairment in any analyses. 3MS test as the primary measure of cognitive function. Among patients with chronic kidney disease, higher baseline SBP was associated with higher risk of incident cognitive impairment specifically in those individuals with eGFR>45mL/min/1.73m2. High blood pressure is a strong risk factor for dementia and cognitive impairment in studies of adults without kidney disease. High blood pressure and cognitive impairment are common in adults with chronic kidney disease (CKD). The impact of blood pressure on the development of future cognitive impairment in patients with CKD remains unclear. We identified the relationship between blood pressure and cognitive impairment in 3,076 adults with CKD. Baseline blood pressure was measured, after which serial cognitive testing was performed over 11 years. Fourteen percent of participants developed cognitive impairment. We found that a higher baseline systolic blood pressure was associated with an increased risk of cognitive impairment. We found that this association was stronger in adults with mild-to-moderate CKD compared with those with advanced CKD.

Nonalcoholic fatty liver disease and cognitive impairment: A prospective cohort study.

Nonalcoholic fatty liver disease (NAFLD) is prevalent and may affect cognitive function. We studied associations of NAFLD with risk of cognitive impairment. Secondarily we evaluated liver biomarkers (alanine aminotransferase (ALT), aspartate aminotransferase (AST), their ratio, and gamma-glutamyl transpeptidase). In a prospective cohort study, the REasons for Geographic and Racial Differences in Stroke, among 30,239 black and white adults aged ≥45,495 cases of incident cognitive impairment were identified over 3.4 years follow up. Cognitive impairment was identified as new impairment in two of three cognitive tests administered every two years during follow up; word list learning and recall, and verbal fluency. 587 controls were selected from an age, race, sex-stratified sample of the cohort. The fatty liver index was used to define baseline NAFLD. Liver biomarkers were measured using baseline blood samples. NAFLD at baseline was associated with a 2.01-fold increased risk of incident cognitive impairment in a minimally adjusted model (95% CI 1.42, 2.85). The association was largest in those aged 45-65 (p interaction by age = 0.03), with the risk 2.95-fold increased (95% CI 1.05, 8.34) adjusting for cardiovascular, stroke and metabolic risk factors. Liver biomarkers were not associated with cognitive impairment, except AST/ALT >2, with an adjusted OR 1.86 (95% CI 0.81, 4.25) that did not differ by age. A laboratory-based estimate of NAFLD was associated with development of cognitive impairment, particularly in mid-life, with a tripling in risk. Given its high prevalence, NAFLD may be a major reversible determinant of cognitive health.

Assessing Risk of Incident Cognitive Impairment Using Stages of Objective Memory Impairment (SOMI) and Cerebrospinal Fluid

AbstractBackgroundThe asymptomatic period for persons with preclinical Alzheimer’s disease (AD) lasts for several years despite the presence of AD biomarkers. These biomarkers are critical for disease detection and monitoring, but collection is burdensome and costly. Sensitive cognitive measures such as Stages of Objective Memory Impairment (SOMI) may be a low‐cost alternative or adjunctive marker of disease‐progression risk. Here, we used longitudinal data from the Knight Alzheimer’s Disease Research Center to investigate the odds of disease progression associated with baseline SOMI stage and cerebrospinal fluid (CSF) biomarkers of Aβ42/Aβ40 ratio, p‐tau181, and t‐tau.MethodsWe used data from 617 cognitively unimpaired participants with baseline Clinical Dementia Rating (CDR) of 0, CSF measures, and longitudinal Free and Cued Selective Reminding Test (FCSRT) scores used to classify participants into different SOMI stages (Table 1). We examined the association between SOMI stage, CSF biomarkers, and incident cognitive impairment based on time to conversion from CDR of 0 to CDR&gt;0 (incident cognitive impairment) using Cox Models.ResultsParticipants, at enrollment (Table 2), were on average 67.2 (SD = 9.4) years old, 56.6% were female, and had average 7.5 years of follow‐up (range 1‐18). At baseline, 325 (52.7%) were SOMI‐0, 206 (33.4%) were SOMI‐1, 64 (10.4%) were SOMI‐2, and 22 (3.6%) were SOMI‐3 or ‐4 (merged groups). A total of 127 (20.6%) individuals converted to CDR&gt;0. The Cox proportional hazards regression models indicated that in comparison with individuals in SOMI‐0 stage, those in SOMI‐3/4 stage were more than twice as likely to show disease progression (HR=2.43 (95% CI, 1.21‐4.89, p=0.013)) (Table 3). Adding individual CSF biomarkers to the models did not affect the association of SOMI‐3/4 with incident cognitive impairment (p&lt;0.05 for all). In models that included SOMI stages and all CSF biomarkers, SOMI‐3/4 (HR=2.13, 95% CI 1.07‐4.12, p=0.033) Aβ42/Aβ40 (HR=9.76e‐6, 95% CI=2.70e‐10 ‐ 0.35, p=0.031) and t‐tau (HR=1.001, 95% CI=1.000‐1.002, p=0.018), but not p‐tau (p=0.645), showed significant association with incident cognitive impairment.ConclusionsSOMI‐3/4 predicts incident cognitive impairment (change in CDR) independently from CSF AD biomarkers. These results support the utility of SOMI stage as an early marker of incident cognitive impairment.

Childhood adversity and cognitive impairment in later life.

ObjectivesThis study examined the association between childhood adversity and cognitive impairment in later life and explored the potential moderation effect of gender and race.MethodsThe study sample included 15,133 participants of the Health and Retirement Study (1998–2016 surveys) who had complete data on key study measures and were more than 50. The outcome variable is a dichotomous indicator of cognitive impairment as assessed by the Telephone Interview for Cognitive Status for self-respondents and the 16-item Informant Questionnaire on Cognitive Decline in the Elderly for proxies. A total of six childhood adversity indicators included grade retention, parental substance abuse, physical abuse, trouble with the police, moving due to financial hardship, and receipt of help due to financial hardship in early life. The estimation of the association between childhood adversity and cognitive impairment involved Cox proportional hazards regression. Results: Grade retention had the largest effect on incident cognitive impairment (HR = 1.3, 95% CI = 1.23–1.38, p < 0.001), followed by physical abuse by a parent (HR = 1.10, 95% CI = 1.00–1.20, p = 0.001). The impact of grade retention was more detrimental to women than men (interaction term HR = 0.89, 95% CI = 0.80–1.00, p = 0.048, female as the reference). Parental substance abuse was associated with a lower risk of incident cognitive impairment for most racial groups (HR = 0.89, 95% CI = 0.83–0.95, p = 0.001), but this association was reversed in “non-Hispanic other” race, consisting mainly of Asians (HR = 1.54, 95% CI = 1.05–2.26, p = 0.025).DiscussionSome aspects of childhood adversity continue to harm cognitive functioning in later life, while some events may have the opposite effect, with evidence of heterogeneity across gender and race.

Changes in Serum Thyroid Function Predict Cognitive Decline in the Very Old: Longitudinal Findings from the Newcastle 85+ Study.

Background: Low serum thyrotropin (TSH) has been associated with an increased risk of cognitive impairment in observational studies of older individuals, but the mechanism underlying this is unclear. We investigated the association between changes in thyroid status and cognitive impairment in very old adults, using prospective data from the Newcastle 85+ study. Method: A cohort of 85-year-old individuals was assessed for health status and thyroid function. Complete data from a comprehensive multidimensional measure of health and repeat thyroid function were available for 642 participants with normal free thyroid hormones and TSH levels ranging between 0.1 and 10 mU/L. Cognitive performance, assessed using Mini-Mental State Examination (MMSE) and Cognitive Drug Research battery was examined by using linear mixed, logistic regression, and Cox proportional hazard models in relation to baseline and 3-year changes in serum TSH, free thyroxine (fT4), and free triiodothyronine (fT3). Results: Over 3 years, declining serum TSH was associated with reductions in fT4 and fT3, and an increased risk of incident cognitive impairment by 5 years (odds ratio1.77 [95% confidence interval: 1.19-2.61]; p = 0.004). A greater reduction in MMSE score was associated with larger TSH decline, at 3 (p = 0.001) and 5 years (p < 0.001), respectively. Steady fT4 concentrations were found in participants with rising TSH. Conclusions: In contrast to physiological expectation, in this group of 85-year-olds, a declining serum TSH was associated with reductions in free thyroid hormones over time. A decreasing serum TSH trajectory over time anticipated cognitive decline in later life. Declining TSH concentrations are a biomarker for cognitive impairment in later life.

Tooth Loss, Denture Use, and Cognitive Impairment in Chinese Older Adults: A Community Cohort Study.

Evidence regarding the associations of tooth loss and denture use with incident cognitive impairment is inconclusive in older adults, and few prospective studies have examined the potential interaction between tooth loss and denture use in these specific populations. Data were assessed from 17 079 cognitively normal older adults aged ≥65 years, participating in the Chinese Longitudinal Healthy Longevity Survey. The outcome of interest was cognitive impairment (assessed by the Chinese version of Mini-Mental State Examination). The number of natural teeth and status of denture use were collected by a structural questionnaire. A total of 6456 cases of cognitive impairment were recorded during 88 627 person-years of follow-up. We found that compared with participants with 20+ teeth, those with 10-19, 1-9, and 0 teeth had increased risks of incident cognitive impairment (p-trend < .001). Participants without dentures also had a higher risk of incident cognitive impairment, compared with those who wore dentures. Effect modification by denture use was observed (p-interaction = .010). Specifically, among those without dentures, the adjusted hazard ratio (95% confidence interval) for participants with 10-19, 1-9, and 0 teeth were 1.19 (1.08, 1.30), 1.28 (1.17, 1.39), and 1.28 (1.16, 1.41), respectively, as compared to those with 20+ teeth. In contrary, among denture users, detrimental effect was only observed among those with 0 teeth (hazard ratio 1.14, 95% confidence interval: 1.16, 1.41). In Chinese older adults, maintaining 20+ teeth is important for cognitive health; denture use would attenuate the detrimental effects of tooth loss, especially for partial tooth loss, on cognitive impairment.

Self-reported hearing difficulty increases 3-year risk of incident cognitive impairment: The role of leisure activities and psychological resilience.

Although hearing difficulty is associated with cognitive impairment, little is known about the potential mechanisms involved. This study assessed the mediating effects of leisure activities and psychological resilience on the association between hearing difficulty and cognitive impairment. Two waves of Chinese Longitudinal Healthy Longevity Survey (2011-2014) were used in the current analysis. Hearing difficulty, leisure activities and psychological resilience were measured at baseline. Cognitive function was assessed using the Chinese version of the Mini-Mental State Examination. The data were analyzed using generalized structural equation modeling with adjustment for confounding factors. Of the 4267 participants at baseline, 33.5% (1430) reported hearing difficulty. The incidence of cognitive impairment was 15.3% (651) during the 3-year follow-up. Hearing difficulty increased the risk of cognitive impairment (odds ratio [OR]=1.59, 95% confidence intervals [CI]: 1.26-1.92). Leisure activities and psychological resilience partly mediated the association between hearing difficulty and cognitive impairment. Hearing difficulty was negatively related to leisure activities (β=-0.23, 95% CI: -0.41 to -0.05) and psychological resilience (β=-0.34, 95% CI: -0.57 to -0.11). Furthermore, leisure activities (OR=0.92, 95% CI: 0.89-0.96) and psychological resilience (OR=0.95, 95% CI: 0.93-0.98) would significantly decrease the risk of cognitive impairment. Hearing difficulty was associated with the incidence of cognitive impairment in older adults. Leisure activities and psychological resilience mediated the relationship. Participation in leisure activity and promoting psychological resilience may be candidate interventions in preventing cognitive impairment among the individuals with hearing difficulty.

Associations between lifestyle risk, β‐amyloid, tau, and cognition in late mid‐life

AbstractBackgroundModifiable lifestyle risk (LR) factors are increasingly viewed as preventive strategies for AD and dementia; however, the impact of LR factors on AD biomarkers or AD biomarker‐related cognitive decline remains unknown. We utilized the Lifestyle for BRAin health (LIBRA) index 1)to investigate whether baseline LR predicts incident cognitive impairment and/or β‐amyloid onset; 2)to examine the effect of longitudinal LR on cognitive decline in the presence of β‐amyloid; 3)to preliminarily examine the cross‐sectional relationship between late‐midlife LR and β‐amyloid and tau biomarker groups.MethodParticipants (n=1244, Table 1) from the Wisconsin Registry for Alzheimer’s Prevention completed serial health and neuropsychological assessments with a subset undergoing PiB PET imaging (n=238) and MK‐6240 (n=186) PET imaging. Cox regressions assessed the predictive utility of baseline LIBRA for incident cognitive impairment (1.5 SD below covariate adjusted 3‐test Preclinical Alzheimer’s Cognitive Composite, PACC‐3) and β‐amyloid duration (i.e. age at assessment – estimated age PiB(+)). Linear mixed models examined the main effects and age interactions of LIBRA and β‐amyloid duration on longitudinal cognitive performance. Group differences in LIBRA were assessed across biomarker groups, where amyloid (A+) and tau (T+) positivity were defined as a global PiB DVR&gt;1.19 and entorhinal cortex MK‐6240 SUVR&gt;1.27, respectively.ResultIn the survival analysis, baseline LIBRA predicted risk for incident cognitive impairment of subjects unimpaired at baseline (HR=1.18; Figure 1). In the amyloid imaging subset, baseline LIBRA did not predict β‐amyloid onset (HR=0.85; Figure 1). Linear mixed effects models indicated a significant main effect of LIBRA (higher LIBRA risk = worse PACC‐3) and a significant interaction of β‐amyloid duration×age on PACC‐3 (longer β‐amyloid duration = faster PACC‐3 decline; Figure 2). In the combined imaging subset (n=186), there were no differences in LIBRA across biomarker groups (Kruskal‐Wallis H: 5.08, p=.166; Figure 3).ConclusionThese findings suggest that a healthy lifestyle is associated with overall cognitive performance but not the rate of cognitive decline or biomarker status. In this sample, LR did not influence the onset of β‐amyloid or hasten AD‐related cognitive decline. Replication of this finding and future work is necessary to better understand the relationships between LR factors, cognitive decline and AD.

Loneliness is associated with risk of cognitive impairment in the Survey of Health, Ageing and Retirement in Europe.

To test whether loneliness is associated with the risk of cognitive impairment up to 11 years later in a European sample of middle-aged and older adults. The study examines whether this association is independent of measures of social isolation, depression, and other risk factors for cognitive impairment and dementia. Participants (N = 14 114) from the Survey of Health, Ageing and Retirement in Europe (SHARE) answered a single item on loneliness at baseline and were assessed for cognitive impairment every 2-to-3 years for 11 years. Participants who scored at least 1.5 standard deviations below the age-graded mean on both a memory recall task and verbal fluency task were classified as impaired. A three-item measure of loneliness was available for a sample of respondents followed up to 4 years. Feeling lonely was associated with increased risk of incident cognitive impairment (HR = 1.31, 95%CI = 1.19-1.44), after accounting for age, sex, education, and SHARE country strata. The association was robust but reduced in magnitude when controlling for clinical and behavioral risk factors, health-related activity limitations, social isolation, social disengagement, and depressive symptoms. The association was not moderated by socio-demographic factors and was also apparent when using the three-item loneliness scale instead of the single-item measure. These findings expand the extant literature on loneliness and the risk of cognitive impairment in older adulthood. Loneliness is one modifiable factor that can be intervened prior to the development of severe impairment or dementia.

Meaning in life and risk of cognitive impairment: A 9-Year prospective study in 14 countries

BackgroundA meaningful and purpose-driven life is associated with better health outcomes. We test whether meaning in life is associated with risk of cognitive impairment using data from a large, multi-national study. MethodsParticipants (N = 22,514) were from the Survey of Health, Ageing and Retirement in Europe (SHARE). Participants from 14 countries reported on their meaning in life. Cognitive impairment was derived from performance on cognitive tasks administered at baseline and at up to three follow-up waves (waves 2–6 assessed between 2010–2015). ResultsLack of meaning in life was associated with a more than 20 % increased risk of incident cognitive impairment over the up to 9-year follow-up (Hazard Ratio = 1.24; 95 % Confidence Interval = 1.17–1.31). Further, compared to participants who reported often feeling meaning in life, participants who reported never feeling meaning in life were at an approximately 75 % increased risk of impairment (Hazard Ratio = 1.75, 95 % Confidence Interval = 1.19–2.57). The association between meaning in life and risk of cognitive impairment was apparent across four regions of Europe (Northern, Southern, Eastern, Western) and in Israel and was not moderated by sociodemographic characteristics. ConclusionsReporting lower meaning in one’s life is associated with risk of incident cognitive impairment. Meaning may be a potential target of intervention for healthier cognitive aging.

Abstract WP482: Early Life Exposure to the Stroke Belt and Later Life Incident Cognitive Impairment: The Reasons for Geographic and Racial Differences in Stroke (REGARDS) Study

Introduction: Incidence of cognitive impairment is higher for residents of the Stroke Belt (SB) compared to those living outside it, but the importance of timing of SB residence is unclear. Methods: Participants were aged 45+ yrs, and enrolled in 2003-2007 in REGARDS. Cognition was assessed annually, by telephone, using the Six-Item Screener (SIS) in 11,488 black or white stroke-free participants currently living in the SB, and 8,949 currently living outside of the SB. Incident cognitive impairment was defined as SIS score of &lt; 4 at last assessment among participants with initial SIS &gt;4. Exposures were defined as SB residence all years, some years, or no years of childhood (ages 0-18) and early adulthood (ages 19-30). Demographic adjusted logistic regression models were stratified by SB residence at enrollment, and were used to estimate the demographic-adjusted odds of incident cognitive impairment. Results: Among those currently residing in the SB, childhood residence outside the SB for some (OR = 0.82; 95% CI: 0.68 - 0.99) or all (OR = 0.76; 95% CI: 0.65 - 0.90) of the time predicted lower odds of incident cognitive impairment. Similarly, early adulthood residence outside the SB for some (OR = 0.86; 95% CI: 0.74 - 0.98) or all (OR = 0.70; 95% CI: 0.58 - 0.84) of the time predicted lower incident cognitive impairment. Conversely, for those currently living outside the SB, the risk of incident cognitive impairment was higher for those who had spent their entire early adulthood in the SB (OR = 1.51; 95% CI: 1.01 - 2.57), with non-significant increased risk for childhood exposure or some early adulthood exposure to the SB (table). Conclusions: These findings suggest that early residence in the SB during childhood or early adulthood increases the risk of cognitive impairment regardless of place of residence in later adulthood. Further research is needed to determine the characteristics of early SB life that are linked to later adult cognitive impairment.

Cognitive reserve regulates the association between hearing difficulties and incident cognitive impairment evidence from a longitudinal study in China.

Cognitive reserve (CR) can prevent the risk of incident cognitive impairment in the elderly. However, the moderator effects of CR on the link between hearing difficulties (HDs) and the risk of incident cognitive impairment are not well understood. This cohort study obtained data from the Chinese Longitudinal Healthy Longevity Survey from 2008 to 2014. The baseline samples included 6309 participants aged 65 years and older at baseline. Cognitive impairment was assessed using the Chinese version of the Mini Mental State Examination. A composite measure of CR was calculated based on education, occupational complexity, and leisure activities of the participants. The marginal structural model was utilized to investigate whether CR moderates the association between HD and incident cognitive impairment. Odds ratios (ORs) and accompanying 95% confidence intervals (CIs) were calculated. Of the 6309 participants at baseline, 1936 (30.7%) developed cognitive impairment during the 6-year follow-up period and 2562 (40.6%) reported HD. The risk of incident cognitive impairment was 1.90-fold (95% CI 1.69-2.14) for participants developing HD compared to those without. Those with middle CR had lower OR (0.72, 95% CI 0.62-0.82) that further decreased to 0.58 (95% CI 0.49-0.69) for those with high CR. Participants with HD with low CR showed the highest OR (4.32, 95% CI 3.42-5.47). In addition, individuals with HD with low education levels or low complex occupations had the highest risk of incident cognitive impairment. CR moderates the negative association between HD and cognitive function. Education and occupation complexity may be more sensitive proxies for CR.

Exercise Comes of Age: Brain Training

Dementia is a growing global concern engendering immense societal cost and personal suffering. It is the leading cause of dependence and disability in the older population in Australia, as it is worldwide. Prevention is critical to interrupt the spiral of physical, emotional, and cognitive suffering globally as the demographic shifts continue to expand this epidemic. Decades of research into pharmacological treatments to either prevent or treat dementia in healthy adults or those with memory loss have not been successful, and thus recent attention has turned to lifestyle and risk factor reduction. Notably, robust animal and epidemiological data strongly support the role of physical exercise in modifying brain structure and cognitive performance across the lifespan. For example, in prospective studies higher self-reported physical activity is associated with a 20–30 % reduction in incident dementia, while objective measurement of total activity-related energy expenditure has been linked to a substantial 91 % reduction in the risk of incident cognitive impairment over 5 yrs. It has been estimated from such prospective cohort studies that reducing physical inactivity by only 25 % would prevent 1 million cases of dementia worldwide annually. Mild cognitive impairment (MCI), defined as objective and subjective cognitive decline with preserved functional independence, offers a unique window of opportunity in high-risk individuals to target neuroplasticity when the brain is still potentially able to adapt to beneficial stimulation. Building on the observational literature above, some exercise trials have led to improved cognitive performance, but the effect sizes in cognitively healthy adults have been statistically negligible, heterogeneous, and of questionable clinical relevance. However, exercise trials in those with established MCI or dementia have reported larger positive effects, particularly when the prescriptions are sufficiently robust. Unfortunately, the mechanisms of exercise benefit, or the reasons for broad individual variation in cognitive adaptations are very poorly defined. Such mechanistic insight, and longterm, robust research is critical if we are to confirm and optimise a brain-training exercise prescription so as to enhance neuroplasticity and improve cognition in high-risk or already impaired individuals.

Poverty increases the risk of incident cognitive impairment among older adults: a longitudinal study in China

Objectives: With a longitudinal design, we aimed to investigate the relationship between poverty and the risk of incident cognitive impairment in China.Methods: We used three waves of the Chinese Longitudinal Healthy Longevity Survey (2008–2014). Cognitive impairment was assessed using the Chinese version of the Mini Mental State Examination. Poverty was measured according to the latest national poverty line settled at an annual per-capita income of 2300 yuan (approximately equivalent to 1.25 dollar/day) in 2011 in China. A marginal structural model was utilized to explore the association between poverty and the risk of incident cognitive impairment. The subgroup analyses were also conducted in this study.Results: The cumulative incidence of cognitive impairment over 6 years was 30.69% (1936/6309). Poverty increased 34% risk of incident cognitive impairment in the elderly (odds ratio = 1.34, 95% confidence interval (CI): 1.15–1.56) after controlling behavioral factors and health status covariates. Participants who were male (OR = 1.38, 95% CI: 1.08–1.76), lived in urban areas (OR = 1.55, 95% CI: 1.22–1.98), and were married (OR = 1.72, 95% CI: 1.28–2.32) had higher poverty risks on incident cognitive impairment in subgroup analyses.Conclusions: Our results provide empirical support for the ongoing discussion about how economic hardship impacts of cognitive functioning, and highlight the negative health risks that economically disadvantaged individuals may experience.

Associations of Hearing Loss and Menopausal Hormone Therapy With Change in Global Cognition and Incident Cognitive Impairment Among Postmenopausal Women.

Hearing loss (HL) and menopausal hormone therapy (conjugated equine estrogens [CEE] and/or medroxyprogesterone acetate [MPA]) are separately associated with cognitive decline and increased risk of incident cognitive impairment. Joint effects of HL and HT could be associated with additive or synergistic decline in global cognition and risk of incident cognitive impairment among postmenopausal women. Using the Women's Health Initiative (WHI) Memory Study, 7,220 postmenopausal women with measures of HL, global cognition (Modified Mini-Mental State Examination score), and cognitive impairment (centrally adjudicated diagnoses of mild cognitive impairment and dementia) from 1996 to 2009. Multivariable linear mixed-effects models were used to analyze rate of change in global cognition. Accelerated failure time models were used to evaluate time to incident cognitive impairment, stratified by HT. Within the CEE-Alone trial, observed adverse effects of CEE-Alone on change in global cognition did not differ by HL, and estimated joint effects of HL and CEE-Alone were not associated with incident cognitive impairment. Within the CEE+MPA trial, while HL did not independently accelerate time to cognitive impairment, the adverse effect of CEE+MPA on global cognition was heightened in older women with HL. Older women on CEE+MPA either with HL (time ratio [TR] = 0.82, 95% confidence interval [CI]: 0.71, 0.94) or with normal hearing (TR = 0.86, 95% CI: 0.76, 0.97) had faster time to cognitive impairment than those with normal hearing and placebo. HL may accentuate the adverse effect of CEE+MPA, not CEE-Alone, on global cognitive decline, not incident cognitive impairment, among postmenopausal women on HT.

Gender and Educational Differences in the Association between Lifestyle and Cognitive Decline over 10 Years: The Doetinchem Cohort Study.

Background:Several modifiable risk factors for cognitive decline have been identified, but whether differences by gender and educational level exist is unclear.Objective:The present study aims to clarify this by prospectively investigating the relationship between health and lifestyle factors and cognitive functioning in different subgroups defined by gender and educational level.Methods:2,347 cognitive healthy individuals (mean age = 54.8, SD = 6.8, range: 41–71; 51.8% female; 26.2% low education) from the Doetinchem Cohort Study were examined for cognitive function at baseline, and at 5- and 10-year follow-up. Health- and lifestyle factors were captured by a poly-environmental risk score labelled ‘LIfestyle for BRAin Health’ (LIBRA). This score consists of 12 modifiable risk and protective factors for cognitive decline and dementia, with higher scores indicating greater risk (range: –2.7 to +12.7). Heterogeneity in associations between LIBRA and decline in verbal memory, cognitive flexibility, and mental speed between males and females and individuals with different levels of education were assessed in linear mixed models.Results:Overall, higher LIBRA scores predicted faster decline in verbal memory, cognitive flexibility, and mental speed over 10 years. Higher LIBRA scores were further associated with increased risk for incident cognitive impairment (one-point increase in LIBRA: HR = 1.09, 1.04–1.14, p = 0.001). In general, these effects were similar across gender and educational level.Conclusion:A composite risk score comprising unhealthy lifestyle and relatively poor health in midlife is significantly associated with a worse course of cognition 10 years later. These associations were for the most part unrelated to gender or educational differences.