Modifiable Risk Factors For Dementia Research Articles

Disparate Dementia Risk Factors Are Associated with Cognitive Impairment and Rates of Decline in African Americans.

This study was undertaken to evaluate the frequency of modifiable dementia risk factors and their association with cognitive impairment and rate of decline in diverse participants engaged in studies of memory and aging. Modifiable dementia risk factors and their associations with cognitive impairment and cognitive decline were determined in community-dwelling African American (AA; n = 261) and non-Hispanic White (nHW; n = 193) participants who completed ≥2 visits at the Mayo Clinic Alzheimer Disease Research Center in Jacksonville, Florida. Risk factors and their associations with cognitive impairment (global Clinical Dementia Rating [CDR] ≥ 0.5) and rates of decline (CDR Sum of Boxes) in impaired participants were compared in AA and nHW participants, controlling for demographics, APOE ɛ4 status, and Area Deprivation Index. Hypertension, hypercholesterolemia, obesity, and diabetes were overrepresented in AA participants, but were not associated with cognitive impairment. Depression was associated with increased odds of cognitive impairment in AA (odds ratio [OR] = 4.30, 95% confidence interval [CI] = 2.13-8.67) and nHW participants (OR = 2.79, 95% CI = 1.21-6.44) but uniquely associated with faster decline in AA participants (β = 1.71, 95% CI = 0.69-2.73, p = 0.001). Fewer AA participants reported antidepressant use (9/49, 18%) than nHW counterparts (57/78, 73%, p < 0.001). Vitamin B12 deficiency was also associated with an increased rate of cognitive decline in AA participants (β = 2.65, 95% CI = 0.38-4.91, p = 0.023). Modifiable dementia risk factors are common in AA and nHW participants, representing important risk mitigation targets. Depression was associated with dementia in AA and nHW participants, and with accelerated declines in cognitive function in AA participants. Optimizing depression screening and treatment may improve cognitive trajectories and outcomes in AA participants. ANN NEUROL 2024;95:518-529.

ASSOCIATIONS OF VISUAL IMPAIRMENTS AND OCULAR DISEASE WITH BRAIN VOLUMES AND DEMENTIA IN UK BIOBANK

Abstract Visual impairments and ocular diseases are emerging potentially modifiable risk factors for dementia, however, causal relationships are poorly understood and vision impairment may also impact dementia evaluations. Few studies have examined associations of multiple measures of visual impairments with markers of neurodegeneration. We investigated associations of visual acuity and history of ocular diseases with dementia and brain MRI outcomes. UK Biobank participants aged 40-70 without dementia at assessment (n=496,938) self-reported history of cataract, glaucoma, age-related macular degeneration Subsets had visual acuity exams and refractive error measured by autorefractor (n=117,163) and brain MRIs (n=33,923). In cox proportional-hazard models adjusted for demographics and other health conditions, history of cataracts was associated with higher risk of all-cause dementia (HR:1.19: 95%CI: 1.09-1.31) but other eye conditions were not associated. History of cataract was associated with significantly smaller total gray matter volume (β=-2483 mm3, 95% CI: -4225 to -741) but not an AD brain signature based on cortical thickness. Worse than 20/40 visual acuity was associated with dementia (HR = 1.40, 95% CI: 1.11-1.77) but myopia defined based on refractive error was not, and neither were associated with total or regional volumes on brain MRI. History of cataract and binary 20/40 vision are associated with dementia risk. Our results suggest that cataract, but not myopia, may increase risk of neurodegeneration independent of typical AD, but more investigation is needed.

TOXIC CHEMICAL EMISSIONS AND DEMENTIA RISK: RESULTS FROM THE CARDIOVASCULAR HEALTH COGNITION STUDY

Abstract Air pollution is a modifiable risk factor for dementia. Yet, studies on specific forms of air pollution (e.g., toxic chemical emissions from industrial facilities) and dementia risk are underexplored. We examined associations between toxicity-weighted concentrations of industrial pollution and dementia outcomes among a large, multi-site cohort of older adults. Participants (n=2,770) were ≥ 65 years old (M=75.3, SD=5.1 years) from the Cardiovascular Health Cognition Study. Toxicity-weighted concentrations were estimated using the Risk Screening Environmental Indicator (RSEI) model which incorporates total reported chemical emissions with toxicity, fate, and transport models. Estimates were aggregated to participants’ baseline census tract, averaged across 1988-1992, and log10-transformed. Dementia status was clinically adjudicated in 1998-1999 (M=5.2 person-periods) by subtype (all-cause, Alzheimer’s, vascular, mixed). We assessed whether RSEI-estimated toxicity-weighted concentrations were associated with: 1) odds of prevalent dementia and 2) incident dementia risk by subtype. After adjusting for individual and neighborhood-level covariates, a 1-unit increase in log10-toxicity was associated with a 34% increase in the odds of prevalent dementia (OR=1.34, 95% CI: 1.01, 1.78). In discrete-time survival models, each 1-unit increase in log10-toxicity was associated with a 65% increased hazard of vascular dementia (HR=1.65, 95% CI: 1.04, 2.61) but was not significantly associated with all-cause, Alzheimer’s disease, or mixed dementia. Living in regions with higher toxic air emissions was associated with greater odds of prevalent dementia and a heightened risk of incident vascular dementia. Results suggest that the RSEI model may be a novel screening tool for examining associations between toxic chemical releases and dementia risk.

Sarcopenia and diabetes-induced dementia risk.

This study aimed to investigate whether sarcopenia independently increases the risk of diabetes-induced dementia in elderly individuals diagnosed with type 2 diabetes mellitus. The study cohort consisted of a large sample of elderly individuals aged 60 years and above, who were diagnosed with type 2 diabetes mellitus between 2008 and 2018. To minimize potential bias and achieve covariate balance between the sarcopenia and non-sarcopenia groups, we employed propensity score matching. Various statistical analyses, including Cox regression models to assess dementia risk and associations, competing risk analysis to account for mortality and Poisson regression analysis for incidence rates, were used. Before propensity score matching, the study included 406 573 elderly type 2 diabetes mellitus patients, with 20 674 in the sarcopenia group. Following propensity score matching, the analysis included a total of 41 294 individuals, with 20 647 in the sarcopenia group and 20 647 in the non-sarcopenia group. Prior to propensity score matching, elderly type 2 diabetes mellitus patients with sarcopenia exhibited a significantly higher risk of dementia (adjusted hazard ratio: 1.12, 95% confidence interval: 1.07-1.17). After propensity score matching, the risk remained significant (adjusted hazard ratio: 1.14, 95% confidence interval: 1.07-1.21). Incidence rates of dementia were notably higher in the sarcopenia group both before and after propensity score matching, underscoring the importance of sarcopenia as an independent risk factor. Our study highlights sarcopenia as an independent risk factor for diabetes-induced dementia in elderly type 2 diabetes mellitus patients. Advanced age, female gender, lower income levels, rural residency, higher adapted diabetes complication severity index and Charlson Comorbidity Index scores and various comorbidities were associated with increased dementia risk. Notably, the use of statins was linked to a reduced risk of dementia. This research underscores the need to identify and address modifiable risk factors for dementia in elderly type 2 diabetes mellitus patients, offering valuable insights for targeted interventions and healthcare policies.

Unsupervised detection of dementia based on longitudinal data from the Survey of Health, Ageing and Retirement in Europe

AbstractBackgroundIn the Survey of Health, Ageing and Retirement in Europe (SHARE), a population‐based survey of aging in multiple countries, dementia status is self‐reported. However, more than half of dementia cases remain underdiagnosed, which may hinder the use of SHARE data to study dementia determinants and outcomes. We use unsupervised machine learning and longitudinal data from SHARE to discover clusters of patients with probable dementia.MethodsWe selected participants aged 50 or more with consecutive follow‐ups across all SHARE prospective waves. We chose variables informative of participants’ daily function and cognitive performance. We applied a Multiple Factor Analysis followed by a Hierarchical Clustering to the whole longitudinal data set. To evaluate our algorithm, we looked at its discrimination power by comparing it to the self‐reported dementia. We also checked if increased risk of transition to probable dementia was associated with non‐modifiable (age, sex) and modifiable (education, hypertension, obesity, hearing loss, diabetes, physical inactivity, smoking, drinking alcohol, social isolation, depression, air pollution) dementia risk factors. Finally, we replicated this study in the English Longitudinal Survey of Aging (ELSA).ResultsThe baseline sample consisted of 15,278 initial participants across 12 countries. The algorithm identified a higher number of probable dementia cases compared with self‐reported cases. Its discriminative power was good discriminative power across all waves (Area Under the Curve &gt; 0.75). Sensitivity attained its highest value at wave 4 reaching 0.71 [0.66–0.77]. Specificity remained high (&gt; 0.9) in all waves. Both non‐modifiable and modifiable dementia risk factors were associated with increased risk of transition to probable dementia. These results were replicated in ELSA.ConclusionDetection of probable dementia with longitudinal data and unsupervised clustering could be used to study dementia in SHARE and ELSA cohorts. Further validation of this method is needed to apply it in other surveys of aging.

A Multivariate Genome‐Wide Association Study of the Shared Genetic Architecture Among Modifiable Risk Factors for Dementia: 590 Loci Associated with Brain Health

AbstractBackgroundTargeting modifiable risk factors may prevent or delay dementia. The mechanisms by which some risk factors influence dementia remain unclear and commonality between risk factors is often overlooked. We aimed to characterize the shared genetic architecture of modifiable risk factors for dementia, and use this to explore whether shared pathways influence dementia pathogenesis and brain health.MethodWe performed two multivariate genome‐wide association studies (GWAS) to characterize the shared genetic architecture of 12 modifiable risk factors for dementia using genomic structural equation modeling (GSEM). One GWAS measured genetic associations with 3 latent subgroups of closely correlated risk factors, whereas our second GWAS measured genetic associations shared across all 12 risk factors (Figure 1). We tested whether the associated variants were enriched in neuronal/glial subtypes and epigenetic marks found in different brain regions using stratified‐GSEM and identified potentially causal genes for each of the latent factors using gene mapping techniques and summary‐data‐based Mendelian randomization. Pathway analysis was conducted to examine whether the prioritized genes were implicated in dementia‐related biological pathways.ResultWe identified 305 genome‐wide significant loci for the 3‐factor model of modifiable dementia risk and 285 genome‐wide significant loci for the Common Factor. Thirty‐four of these loci were novel (not previously associated with any phenotype by GWAS). Post‐GWAS analyses uncovered multiple links between the shared risk factor loci and dementia pathogenesis. Stratified‐GSEM showed that shared risk factor variants are significantly enriched in regions of the brain that degenerate in dementia, including the hippocampus and prefrontal cortex. Gene mapping identified potentially shared causal genes between risk factor loci and Alzheimer’s disease (AD) loci. Pathway analysis indicated that our prioritized genes were enriched in AD pathways, protein aggregation and neuronal cell signaling. Mendelian randomization provided evidence for a causal role of the shared risk factor variants in AD pathogenesis.ConclusionWe highlight multiple genomic regions where genetic overlap between modifiable risk factors seems to directly influence dementia‐related pathways in regions of the brain that are known to degenerate in dementia. Our findings provide novel insights into the potential biological mechanisms by which modifiable risk factors may increase risk for dementia.

Cataract, cataract surgery, and risk of incident dementia: a prospective cohort study of 300,823 participants

AbstractBackgroundConsidering the increasing rate of cataract surgery and postoperative efficacy, the cataract may be one of the most modifiable risk factors for dementia if surgery reverses the increased risk of dementia caused by cataract.MethodWe used multivariate Cox proportional hazard regression models to estimate hazard ratios (HRs) and 95% confidence intervals (CIs) for the associations, with healthy controls as a reference. The same method was used to explore the effects of surgery on the dementia outcomes of cataract patients.ResultMultivariable Cox proportional hazard models showed that the non‐surgical cataract group had a 21.4% increased risk of ACD (HR: 1.214, 95% CI = 1.012‐1.456, P = 0.037) and a 47.9% increased risk of AD (HR: 1.479, 95% CI = 1.105‐1.981, P = 0.009) in the fully adjusted model. However, there was no difference in dementia risk between the cataract surgery group and the healthy control. Cataract surgery was associated with decreased risk of ACD (HR: 0.632, 95% CI = 0.421‐0.947, P = 0.026) and AD (HR: 0.399, 95% CI = 0.196‐0.812, P = 0.011) compared with non‐surgical group.ConclusionOur study supports the hypothesis that cataract surgery reverses the risk of dementia, providing new insights into the prevention and treatment of dementia. Cataract should be considered a significant modifiable risk factor for dementia in dementia prevention strategies.

Kidney function and risk of incident dementia in 202,702 UK Biobank participants

AbstractBackgroundPoorer kidney function could represent a novel modifiable risk factor for dementia, however previous findings are inconclusive. In the current study, we utilized a large population‐based cohort with long follow‐up to investigate whether glomerular filtration rate (GFR), an indicator of kidney function, and albuminuria, an indicator of kidney damage, were associated with an increased risk of all‐cause dementia.MethodThe sample consisted of 202,702 UK Biobank participants aged ≥60 years and free from dementia and end‐stage kidney disease at baseline between 2006‐2010. Estimated GFR was derived from serum creatinine and cystatin C (eGFRcr‐cys) and categorized as ≥90 (normal/high function), 60‐89 (mildly decreased function) and &lt;60 ml/min/1.73m2 (moderately/severely decreased function). Albuminuria was defined using the urinary albumin to creatinine ratio (ACR). ACR was categorized into &lt;3 (normal/mildly increased), 3‐30 (moderately increased), and &gt;300 (severely increased) mg/mmol. Incident dementia was determined through cohort‐wide linkage to hospital and death records. The associations were assessed using Cox proportional‐hazard models adjusted for age, sex, ethnicity, socioeconomic status, education, household income, country, smoking status, alcohol intake, body mass index, hypertension, diabetes, and APOE‐ε4 allele status.ResultOver 15 years of follow‐up, 6,042 participants developed incident dementia. The fully‐adjusted Hazard Ratios (HR) were 1.00 (95% Confidence Interval [CI] 0.94‐1.06) and 1.42 (95% CI 1.28‐1.58) for eGFRcr‐cys 60‐89 and &lt;60 respectively, compared to ≥90 ml/min/1.73m2. Moderately/severely decreased eGFRcr‐cys remained associated with incident dementia after restricting to participants with more than 10 years of follow‐up (HR = 1.33, 95% CI 1.13‐1.56). The HRs for moderate and severely increased ACR were 1.16 (95% CI 1.07‐1.26) and 2.24 (95% CI 1.79‐2.80), respectively, compared to normal/mildly increased ACR (&lt;3mg/mmol). Dose‐response associations were observed when combining eGFRcr‐cys and ACR, with those in the severest eGFRcr‐cys and ACR group having the greatest risk of dementia (HR = 4.70, 95% CI 2.34‐9.43).ConclusionKidney dysfunction and albuminuria were associated with a higher risk of incident all‐cause dementia. These findings provide additional evidence that kidney dysfunction could be a potential modifiable risk factor for dementia or target for identifying those at high risk of the condition.

Indigenous individuals present distinct modifiable risk factors of dementia than white individuals: an ELSI‐Brazil study

AbstractBackgroundRisk factors for dementia have distinct frequency and impact according to racial origins. Our aim was to identify differences of modifiable risk factors of dementia related to Indigenous and White individuals, estimate their Population Attributable Fraction (PAF) and highlight the differences between races.MethodsAn epidemiological cohort named ELSI‐Brazil was used to estimate the prevalence of 10 modifiable risk factors for dementia among 2 races ‐ White and Indigenous. he ELSI‐Brazil cohort consists of 9412 individuals (63.55+‐10.14 years of age). This cohort comprises individuals at/ or above 50 years of age from across the country. Complex sampling warrants nationwide representativity for diseases with low prevalence. Races were self‐reported according to the Brazilian Census. Sample weighting was used to estimate the prevalence and PAF of each risk factor in each race.ResultsAmong 3810 individuals included, 220 were Indigenous individuals. The Indigenous were younger (mean age 62.6 [±9.6] years) and less educated (mean 4.3 [±4.0] years) than the White (mean age 64 years [±10.2], mean education years 6.2 [±4.4]). Both were composed by most females. The most important weighted PAF were hearing loss for both races (Indigenous 16.7%; White 15.2%). The most prevalent risk factor for both were less education, which were higher in Indigenous individuals (69.5%) than in White individuals (55.1%). By contrast, social isolation was less prevalent in Indigenous (1.5%) than White (5.1%). Overall adjusted PAF was lower in Indigneous (38.9%), compared to White (49,2%).ConclusionWhite and Indigenous presented different prevalence of risk factors, though they had hearing loss as the most impacting risk factor for dementia. However, it seemed that Ocidental risk factors didn’t produce the same effect in indigenous individuals as in white individuals. Thus, indigenous individuals presented a distinct profile of risk factors of dementia than individuals from other self‐reported races.

Socioeconomic variation in modifiable risk factors for dementia

AbstractBackgroundMost studies on modifiable risk factors for dementia are in relatively affluent populations, but dementia risk is higher among those who are more materially deprived. We aimed to consider whether this is accounted for by potentially modifiable risk factors, and compare the overall population attributable fraction (PAF) in the least and most socioeconomically deprived participants within the UK Biobank (UKB).MethodThe UKB is a cohort study with 502,656 volunteer participants registered between 2006‐2010, aged 40‐60 years at baseline, and followed for up to 16.8 years. Material deprivation was quantified using the Townsend Deprivation Index grouped into quintiles, with higher scores meaning higher deprivation. We assessed interactions between Townsend quintiles (using least deprived as reference), and each modifiable risk factor. To estimate the PAFs of 12 modifiable risk factors (diabetes, hypertension, depression, hearing loss, obesity, traumatic brain injury, less education, social isolation, physical inactivity, air pollution, and smoking), we first estimated hazard ratios (HRs) (adjusted for age, gender, and ethnicity) stratified by Townsend. HRs were then converted to relative risk for PAF calculation.Results6,624 incident cases of dementia developed in 1.6%(95%CI = 1.5‐1.7)(n = 11679/10369) of participants in the most deprived group, compared to 1.2%(95%CI = 1.1‐1.3)(n = 1174/98074) in the least deprived group. The mean age at dementia diagnosis were 72.7 years(SD,6.3){in most deprived}, and 73.8 years(SD,5.1){in least deprived}. The combined PAF(95%CI) for dementia was 40.3%(40.0‐40.6){most deprived}, versus 27.2%(27.0‐27.5){least deprived}. The most deprived, compared to the least deprived, had higher PAFs for: (a)Midlife hypertension: 7.7%(7.6‐7.9) vs 4.1%(3.9‐4.2); (b)Less education: 5.8%(5.6‐5.9) vs 3.4%(3.2‐3.6); (c)Diabetes: 4.4%(4.3‐4.6) vs 3.1%(3.0‐3.2); (d)Physical inactivity: 3.5%(3.4‐3.6) vs 0.7%(0.6‐0.7);) (e)Social isolation: 3.4%(3.3‐3.5) vs 1.0%(1.0‐1.1); (f)Midlife obesity: 2.1%(2.0‐2.2) vs 1.2%(1.2‐1.3); and (g)Smoking 1.8%(1.7‐1.9) vs 0.5%(0.5‐0.6). Air pollution had a PAF of 1.8%(1.7‐1.9) in the least deprived, and 0.0% in the most deprived. The remaining risk factor PAFs did not differ between the most and least deprived.ConclusionsIn this volunteer cohort, which is relatively wealthy, a higher proportion of dementia cases were attributable to major modifiable risk factors in more socioeconomically disadvantaged participants. Targeted interventions particularly addressing midlife hypertension, education, physical activity and social isolation might mitigate known inequalities in dementia risk according to socioeconomic status.

Association between Anemia and Dementia in Korea older adults: A national cohort study

AbstractBackgroundAs the global elderly population increases, the prevalence of dementia is also increasing. Korea is one of the rapidly aging countries in the world, and 10.33% of elderly people aged 65 and older are receiving treatment for dementia as reported in 2021. Since disease modifying drugs have not yet been developed for dementia, the importance of modifiable risk factors that can lower the risk of dementia is being emphasized, and one of them is anemia in the elderly. We analyze national cohort data of approximately 20 years to disclose the relationship between anemia and dementia in Korean elderly, and suggest that anemia is a modifiable risk factor for dementia needed active intervention.MethodWe analyzed a large population‐based cohort study of aged ³65 years who participated in the national health screening program including blood tests and cognitive function tests from 2007 to 2008 in Korean National Health Insurance Service database 2006‐2020. The risk of AD according to the presence and severity of anemia was evaluated using a multivariable Cox regression model, after adjustments for sex, BMI, HTN, DM, LDL, TG, SCr, GFR and past medical history (depression, HTN, DM, cardiovascular disease, cerebrovascular disease).ResultAs a result of the analysis, dementia occurred in 27.9% of the total subjects (316,881 persons) during the follow‐up period until 2020. Also, dementia occurred in 27.5% of the normal group, but 30.1% of the anemia group. As a result of survival analysis, even after adjusting for sex, there was a statistically significant difference between the presence of anemia and the prevalence of dementia (HR 1.07, 95% CI 1.05‐1.09). In addition, even after adjusting for sex, BMI, HTN, DM, LDL, SCr, GFR, and past medical history, there was a statistically significant association between anemia and dementia (HR 1.05, 95% CI 1.03‐1.07).ConclusionWe reported that the presence of anemia statue and the severity of anemia in the elderly were related to the occurrence of dementia through a national date of Korea. We suggest that anemia is a modifiable risk factor for dementia and requires intensive intervention in the elderly.

Frequency of social isolation among older adults in Nepal

AbstractBackgroundSocial isolation is a recently documented modifiable risk factors for dementia but little is known about its prevalence in low and middle income countries (LMICs).1 Older adults in Nepal are increasingly at for risk for social isolation given trends of adult child migration to other communities. The resultant social isolation increases risk for depression, psychological distress, and dementia2‐3. This study aimed to estimate the prevalence of social isolation among older adults of Nepal and its associated factors.MethodsA quantitative cross‐sectional study in Dhulikhel municipality of Nepal. Two geographical regions within the city were randomly selected. Systematic random sampling was used for the selection of respondents. We employed the Lubben Social Network Scale (LSNS‐18), a brief tool validated in LMIC, to quantify social isolation.4 Data were analyzed with Statistical Package for Social Sciences (SPSS) v25.ResultsMore than half of respondents (52.3%) were age 60‐70 years, 56.1% were male, 55.1% were illiterate, and 59.8% were living in a nuclear family. More than one third (37.4%) met criteria for socially isolation. Social isolation associated with age (p = 0.026), being a widow (p = 0.002), living in a nuclear family (p = 0.001), and the presence of chronic diseases (p = 0.014). Whereas gender and education were not significantly associated with social isolation.ConclusionMore than one third of older adults in this representative community met criteria for social isolation despite the family‐based societal norms that are typical of Nepal. Addressing this issue may promote brain health among older adults. Further research is recommended to examine the cognitive health of this isolated population.

To evaluate the prevalence, subtypes and risk associations of mild cognitive impairment in elderly Indian individuals with type 2 diabetes

AbstractBackgroundDiabetes is an important modifiable risk factor for dementia. The prevalence of mild cognitive impairment (MCI) in type 2 diabetes (T2D) is high (You et al, 2021). This data is largely derived using screening tools (MMSE or MoCA), with little information on MCI subtypes. Evidence from the South Asian region is particularly scarce, where prevalence of diabetes is high, and is seen a decade earlier compared to Caucasians.MethodWe have established a cohort of elders (³ 60 years of age), with and without diabetes, visiting a tertiary care hospital in North India (from 2019, ongoing). The participants underwent an interview to collect information on their demographic profile, risk associations, vascular health, and other comorbidities. Culturally validated neuropsychological battery was used for cognitive evaluation. MoCA was done in a subset of patients.ResultWe recruited 840 participants in the cohort, 683 with T2DM and 157 without T2DM (controls). The mean age of the cohort was 65.3±4.5 years, 65.2% were males. Risk profile is described in Table 1. The cognitive z scores of participants with T2DM ranged from ‐0.25 to +0.44. The worst affected domain was attention, working memory and executive functions (Table 2). Using an actuarial definition of MCI (Bondi MW et al, 2014), the prevalence in participants with T2D was 29.7%. 17.3% had amnestic impairment, 14.8% dysexecutive, 14.2% language, 2.4% visuo‐perceptual and 9.1% multidomain impairment. The cognitive raw scores (by dementia risk stratification) are provided in Table 3. On logistic regression, lower education 3.45(2.09,5.68), depression 2.04(1.26,3.29), poor sleep quality 1.77(1.15,2.71), family income 1.70(1.22,2.38), followed by age 1.05(1.00,1.10) had a significant association with global low cognition.ConclusionRoughly one‐third of elders with T2D visiting tertiary care services in North India have mild cognitive impairment. Amnestic subtype is the most frequent. Attention, working memory and executive functions are worst affected. Enhancing the cognitive reserve, mood and sleep quality may be important targets in prevention of cognitive decline in the elderly population with T2D.

Brain‐age mediates the association between modifiable risk factors and cognitive decline early in the AD continuum

AbstractBackgroundNeuroimaging‐derived brain‐age is a useful biomarker to study the brain’s biological aging process. Brain‐age has shown cross‐sectional associations with cognitive function and modifiable risk factors for dementia. We aimed to study, in cognitively unimpaired (CU) individuals, the mediating role of brain‐age in the association between modifiable risk factors and cognitive changes, and the impact of AD pathology on this role.MethodWe included 416 CU individuals from the ALFA+ study with available structural MRI, measurements of the global cognitive Preclinical Alzheimer’s Cognitive Composite (PACC) (370 individuals had a follow‐up PACC assessment 3.28±0.27 years later), and lifestyle and cardiovascular risk factors assessments. We computed brain‐age delta as the difference between chronological and predicted brain‐age using a previously pre‐trained machine learning algorithm on structural MRI data. Partial Least Squares Path Modeling (PLS‐PM) was employed to investigate the mediation effect of brain‐age delta between a computed latent variable from modifiable risk factors (cardiovascular, mental health and mood, metabolic/endocrine disease history, and alcohol consumption factors; Table 1) and a latent variable from longitudinal PACC. Statistical bias adjustment was performed to control for the confounding effects of age and sex by using multiple linear regression. The analysis was performed on the whole sample (ALL) and after stratification by amyloid‐ß (Aß) status. Participants were classified as amyloid‐ß positive (Aß+) if CSF Aß42/40&lt;0.071 (Milà‐Alomà et al, 2020). Significance of mediation was examined by 95% confidence interval bootstrap.ResultThe effect of risk factors (latent risk) on longitudinal cognition (latent cognition) was partially mediated by brain‐age delta only in Aß+ individuals (57.286%) (Figure 1C). Higher latent risk was associated with older brain‐age delta (p = 0.003) and older brain‐age delta was associated with worse latent cognition (p = 0.007). Conversely, the indirect effect was not significant in ALL nor in Aß‐ individuals, where brain‐age delta was not significantly associated with latent cognition (Figure 1A‐B). Still, higher latent risk was associated with older brain‐age delta (ALL: p&lt;0.001; Aß‐: p = 0.004) and associated with worse latent cognition (ALL: p = 0.012, Aß‐: p = 0.001).ConclusionIn CU individuals in the AD continuum, biological brain aging mediates the association between modifiable risk factors and cognitive decline.

The association between air pollution and dementia: results from the Cognitive Function and Ageing Study II and Wales

AbstractBackgroundAir pollution has been recognised as one of the key modifiable risk factors for dementia. In the UK, there is a lack of evidence from population‐based cohort studies including older people from different backgrounds and living environments. Using two multicentre ageing cohorts in England and Wales, the aim of this study is to investigate the potential impact of air pollution on dementia in later life.MethodThis study was based on the Cognitive Function and Ageing Study (CFAS) II (2008‐2011) and Wales (2011‐2013), two longitudinal studies of people aged 65 or above across five centres in England (Cambridgeshire, Newcastle upon Tyne, Nottingham) and Wales (Gwynedd, Neath Port Talbot). A two‐year follow‐up wave was carried out for both studies. Dementia was identified using the Geriatric Mental State and its diagnostic algorithm, Automated Geriatric Examination for Computer Assisted Taxonomy (GMS‐AGEACT). Based on the participants’ postcodes at the baseline, exposure to four air pollutants in 2012, including nitrogen dioxide (NO2), ozone (O3), particulate matter with a diameter ≤10 microns (PM10) and ≤2.5 microns (PM2.5), was estimated using the Community Multiscale Air Quality pollution modelling at a resolution of 20×20 m. Multistate modelling was used to investigate the effects of air pollution exposure on risk of developing dementia over the follow‐up period, incorporating mortality (from national death certification) and adjusting for age, sex, education, study centre and area deprivation.ResultAmong the 11329 participants in CFAS II (N = 7753) and Wales (N = 3576), the median exposure was 17.7 (IQR = 11.6) µg/m3 for NO2, 43.8 (IQR = 11.1) µg/m3 for O3, 15.5 (IQR = 3.1) µg/m3 for PM10 and 10.1 (IQR = 2.8) µg/m3 for PM2.5 and large variation was observed across the five centres. Per unit increase in NO2 exposure was associated with a higher risk of dementia in CFAS II (HR: 1.07; 95%CI: 1.03, 1.12) but not the Welsh cohort (HR: 0.93; 95%CI: 0.86, 1.00) after adjustment. For the other air pollutants, the associations were unclear.ConclusionOur study suggests limited evidence for the impacts of air pollution on dementia. Other environmental factors may influence individual exposure to air pollution and altogether have a complex effect on cognitive health in later life.

A Comparison of the Prevalence of Diabetes between Aging Rural and Urban Indians.

AbstractBackgroundDiabetes is one of the important modifiable risk factors for dementia. Its prevalence has been increasing rapidly in the past few decades across the world, particularly in India. However, among Indians, there are prominent lifestyle differences between rural and urban residents. Hence, understanding diabetes prevalence in these two distinct populations is essential to understand the differential risk for dementia in rural and urban Indians.MethodCross‐sectional (baseline) clinical data from two ongoing prospective cohort studies, namely Srinivaspura Aging, Neuro Senescence and Cognition (SANSCOG) study in rural India and Tata Longitudinal Study of Aging (TLSA) in urban India was utilized for the present study. A total of 6002 participants – 4913 rural (SANSCOG) and 1089 urban (TLSA) were included. Diagnosis of diabetes was made using self‐reported history and / or fasting blood glucose level of &gt; 126 mg/dl. Chi‐square test of independence was used to assess the group differences between the rural and urban participants – both overall and gender‐wise and age group‐wise.ResultThe mean age of participants was 63.93 ± 9.56 years and 58.74 ± 9.88 years for the urban and rural cohorts, respectively. Prevalence of diabetes was significantly higher in urban than rural subjects – overall (33.6% vs. 19.3%, p&lt;0.001) as well as among males (38.4% vs. 24.1%, p&lt;0.001) and females (28.7% vs. 14.8%, p&lt;0.001). Similarly, on age stratification, urban subjects had significantly higher prevalence than rural subjects in the age groups &lt;65 years (28.1% vs. 18.3%, p&lt;0.001) and ≥65 years (39.5%vs. 21.3%, p&lt;0.001).ConclusionUrban subjects had significantly higher diabetes prevalence than rural subjects across both genders and age groups. In view of the association of diabetes with dementia risk, these findings could imply that urban Indians may be at higher risk for pathological cognitive impairment and dementia as compared to their rural counterparts. However, longitudinal follow of these participants with cognitive monitoring is required to establish a causal association.

Cross‐Sectional Associations Among Sleep Quality, Hippocampal Volume, and Memory Complaints in the Offspring Study

AbstractBackgroundPoor sleep quality, a modifiable risk factor for dementia, that is prevalent in non‐Hispanic Black and Hispanic adults, is associated with greater memory complaints and smaller hippocampal volumes in predominantly non‐Hispanic White samples. These associations among sleep quality, memory complaints, and hippocampal volumes are understudied in non‐Hispanic Black and Hispanic adults—populations disproportionately affected by poor sleep quality and cognitive performance. The objective of the current study was to examine associations among sleep quality, memory complaints, and hippocampal volumes in a racially and ethnically diverse, community‐based sample. Given sociocultural and environmental differences that affect sleep, brain measures, and cognitive performance, we hypothesize that poorer sleep quality is associated with more memory complaints and smaller hippocampal volumes, especially in Black and Hispanic adults.MethodParticipants included Black, Hispanic, and White adults from the Northern Manhattan community (n = 1175; 56±11 years; 67% women; 14±3 years of education; 17% Non‐Hispanic White; 20% Non‐Hispanic Black; 63% Hispanic). Participants self‐reported their sleep quality with the 9‐item Pittsburgh Sleep Quality Index, which measures average sleep disturbance over the past month. Participants self‐reported experiences with forgetting (e.g., names, faces, directions) with an abbreviated version of the Memory Functioning Questionnaire. In a subsample of participants, hippocampal volumes were measured on T1‐weighted MRI scans with FreeSurfer software. Sleep quality, hippocampal volume, and memory complaints were treated as continuous variables. We ran multivariable regression analyses adjusted for age, education, gender identity, depression severity, and intracranial volume for analyses with hippocampal volume.ResultAcross racial and ethnic groups, poorer sleep quality was associated with more memory complaints (n = 1175, B = ‐0.31, CI: [‐41,‐.22]). These associations were similar when analyses were stratified by racial and ethnic group. Among Hispanic adults, there was a trending association between poorer sleep quality and smaller left hippocampal volumes (n = 246, B = ‐8.94, CI: [‐18.75,0.88]).ConclusionPoorer sleep quality was associated with more memory complaints across racial and ethnic groups and showed a trending association with smaller hippocampal volumes in Hispanic adults. Future studies with larger samples should replicate these findings with longitudinal data to quantify the temporal relationship of sleep quality with memory complaints and structural brain changes.

Cognitive function in older adults with hearing loss; outcomes for treated versus untreated groups at 3‐year follow‐up.

AbstractBackgroundHearing loss has been identified as the largest potentially modifiable risk factor for dementia and affects 50% adults aged 50‐64 years, and 70% aged 70 years and older. The quality of evidence the effect of hearing aid use on cognition in older adults is currently poor due to methodological limitations. Few studies have objectively studied these outcomes beyond 6‐12 months. This prospective longitudinal observational cohort study investigated the effects of hearing aid use on cognitive performance in older adults over 3 years.Method183 first‐time hearing aid users aged 60 years and older with mild to severe hearing loss were assessed using gold standard measures before hearing aid fitting, with subsets of this group re‐assessed after 18 and 36 months as they reached these timepoints. Outcomes for the treatment group were compared with those of participants of a large longitudinal cohort study of community‐living older adults (AIBL) using the same measures. Objective assessment measures included cognitive function, hearing loss, hearing aid use, genetic phenotyping, and speech perception. Subjective measures included hearing disability, mood, quality of life, social isolation, and loneliness.ResultThe treatment group showed good hearing aid compliance, significant improvement in speech perception (quiet and noise) and decreased self‐reported listening disability despite further significant hearing loss over the 3‐year follow‐up. There was significant improvement in cognitive performance from baseline for the treatment group versus the comparative group for working memory, attention, psychomotor function, and visual learning. Comparatively, AIBL participants showed statistically significant decline across all cognitive functions.ConclusionOlder adults with untreated hearing loss are expected to decline cognitively at 2‐5 times the rate of adults without hearing loss. Comparatively, cognitive performance in treated participants in this study instead improved after 3 years of hearing aid use, while the comparative group declined. These results suggest that treatment of hearing loss with hearing aids may delay cognitive decline.

Plasma phosphorylated tau 181 and modifiable risk factors for dementia in a large scale cohort of Australian older adults

AbstractBackgroundUp to 40% of dementia cases could be prevented by addressing modifiable risk factors. Alzheimer’s disease (AD), the most common form of dementia, is preceded by up to decades of silent pathological change providing an ideal window for early detection and intervention. In this study, our objective was to examine the associations between modifiable risk factors and plasma phosphorylated p‐tau 181, a hallmark biomarker of early AD.MethodParticipants were recruited from the Island Study Linking Ageing and Neurodegenerative Disease (ISLAND), a prospective public health initiative in Tasmania, Australia’s southernmost island state. ISLAND participants were invited to complete a set of surveys online: a questionnaire on dementia risk factor adherence, demographic surveys and cognitive tests via the Cambridge Neuropsychological Test Automated Battery (CANTAB); Paired Associates Learning (PAL) and Spatial Working Memory (SWM). At four clinics across the state, participants also provided blood samples for measurement of plasma phosphorylated p‐tau 181 and genotyping for APOE.ResultA total of 738 participants (mean age 65.41 years, mean education 17.36 years, 71.8% female, 26.4% ε4+) took part in the study. We found gender‐specific effects on cognition, whereby identifying as male was associated with significantly lower learning ability (PAL) whilst identifying as female was associated with significantly lower executive function (SWM). In multivariate linear models, increasing alcohol consumption (measured in standard drinks per week) was significantly associated with lower plasma p‐tau 181. In adjusted models, no other modifiable risk factors examined were associated with p‐tau 181. Increasing age, identifying as male and possessing at least one APOE ε4 allele were all associated with higher plasma concentrations of p‐tau 181ConclusionHigher alcohol consumption, higher age, identifying as male and having an APOE ε4 allele were all associated with lower plasma phosphorylated tau 181. This contributes to evidence that both modifiable and non‐modifiable dementia risk factors are related to the biological precedents of AD. These associations were related to gender and genetics, therefore a panel of modifiable and non‐modifiable variables should be included in screening or diagnostic testing for pre‐clinical AD. More research is needed regarding specific alcohol types and biomarkers of AD.

Prevalence of risk factors for dementia and association with cognitive alterations in an elderly population from the South of Brazil

AbstractBackgroundThe number of elderly people is increasing globally, including those who live with their dementia. It is currently the seventh leading cause of death worldwide and a leading cause of disability and dependence among older people. “The Lancet Commission’s 2020 update on prevention and monitoring care” evidenced 12 modifiable risk factors for dementia, suggesting that up to 40% of cases could be prevented or delayed if exposure to such factors were eliminated. In view of the increase in the elderly population and dementia cases, it is understood that preventive actions focusing on modifiable risk factors and early detection of dementia cases are necessary.MethodCross‐sectional, quantitative, descriptive study. Cognitive screening was carried out in patients over 60 years of age in an area of the territory of a Basic Health Unit using the Mini Mental State Examination (MMSE) and a survey of 12 (twelve) risk factors were investigated with questions related to: schooling, hypertension, hearing loss, smoking, obesity, physical inactivity, diabetes, social isolation, excessive alcohol consumption, head trauma, exposure to tobacco and pollution. The interviews were performed from August to October 2022. About 146 individuals were selected and 73 interviews were carried out. Exclusion criteria were: bedridden elderly, those with compromised mobility or inability to understand. Statistical analysis was performed using the SPSS program using the Pearson’s chi‐square tests at a significance level of 5%.ResultThe present study identified a significant association between altered MMSE and low education, with a p‐value of 0.016. Of the illiterate patients, 47.6% had changes in the MMSE. Among individuals with 1 to 4 years of schooling, 82.8% had altered MMSE.ConclusionIt can be concluded that low education is a risk factor for dementia, as evidenced in other studies. However, the need for further studies on cognitive assessment instruments should be considered, since low educational level can influence their results.