Modifiable Risk Factors For Dementia Research Articles

Multidomain Dementia Risk Reduction in Primary Care is Feasible: A Proof-of-concept study.

Dementia risk reduction is a public health priority, but interventions that can be easily implemented in routine care are scarce. To evaluate the feasibility of integrating dementia risk reduction in regular consultations in primary care and the added value of a dedicated smartphone app ('MyBraincoach'). 188 participants (40-60 years), with modifiable dementia risk factors were included from ten Dutch general practices in a cluster-randomized trial (NL9773, 06/10/2021). Practices were randomly allocated (1 : 1) to provide a risk-reduction consultation only or to additionally provide the app. During the consultation, participants learned about dementia risk reduction and how to improve their risk profile. The app group received daily microteaching-notifications about their personally relevant risk factors. Feasibility was evaluated after 3 months using questionnaires assessing knowledge on dementia risk reduction and health behavior change. The primary outcome was change in the validated "LIfestyle for BRAin health" (LIBRA) score. In-depth interviews were conducted with participants and primary care providers (PCPs). The interventions were positively perceived, with 72.0% finding the consultation informative and 69.2% considering the app useful. Drop-out was low (6.9%). LIBRA improved similarly in both groups, as did Mediterranean diet adherence and body mass index. Knowledge of dementia risk reduction increased, but more in the app group. Interviews provided insight in participants' and PCPs' needs and wishes. Integrating dementia risk reduction in primary care, supported by a smartphone app, is a viable approach towards dementia risk reduction. Larger trials are needed to establish (cost-)effectiveness.

Poor sleep quality is an important modifiable risk factor for dementia: Population attributable fraction of poor sleep in a Brazilian population-based study.

The populational impact of poor sleep quality and the risk of dementia is unclear. We analyzed the Population Attributable Fraction (PAF) of poor sleep quality for dementia, and its association with other two sleep parameters through self-reported and single questions collected in a large-scale Brazilian cohort (ELSI-Brazil). A subset of the ELSI-Brazil with complete responses to sleep quality was retrieved for this study. This is a large representative sample of the Brazilian elderly population with an extensive assessment of sociodemographic and health risk variables. Prevalence of poor sleep quality was estimated according to the complex sample design, and its PAF was measured using a meta-analytic relative risk. A total of 6024 (56.3% women, mean 62.8±9.5years of age) individuals had complete responses. The prevalence of poor sleep quality was 24.9% (95%CI 23%-26%), and the PAF of poor sleep quality including other 10 modifiable risk factors of dementia was 52.5% in Brazil. Secondary analyses identified that sleep quality, restorative sleep and sleep drug usage varied considerably according to age ranges, race, and gender. Poor sleep quality is an important populational modifiable risk factor for dementia in Brazil. Targeted interventions may provide an important impact in preventing dementia in low- and middle-income countries.

Population attributable fractions of modifiable risk factors for dementia: a systematic review and meta-analysis

More than 57 million people have dementia worldwide. Evidence indicates a change in dementia prevalence and incidence in high-income countries, which is likely to be due to improved life-course population health. Identifying key modifiable risk factors for dementia is essential for informing risk reduction and prevention strategies. We therefore aimed to estimate the population attributable fraction (PAF) for dementia associated with modifiable risk factors. In this systematic review and meta-analysis, we searched Embase, MEDLINE, and PsycINFO, via Ovid, from database inception up to June 29, 2023, for population-derived or community-based studies and reviews reporting a PAF value for one or more modifiable risk factor for later-life dementia (prevalent or incident dementia in people aged ≥60 years), with no restrictions on dementia subtype, the sex or baseline age of participants, or the period of study. Articles were independently screened for inclusion by four authors, with disagreements resolved through consensus. Data including unweighted and weighted PAF values (weighted to account for communality or overlap in risk) were independently extracted into a predefined template by two authors and checked by two other authors. When five or more unique studies investigated a given risk factor or combination of the same factors, random-effects meta-analyses were used to calculate a pooled PAF percentage estimate for the factor or combination of factors. The review protocol was registered on PROSPERO, CRD42022323429. 4024 articles were identified, and 74 were included in our narrative synthesis. Overall, PAFs were reported for 61 modifiable risk factors, with sufficient data available for meta-analysis of 12 factors (n=48 studies). In meta-analyses, the highest pooled unweighted PAF values were estimated for low education (17·2% [95% CI 14·4-20·0], p<0·0001), hypertension (15·8% [14·7-17·1], p<0·0001), hearing loss (15·6% [10·3-20·9], p<0·0001), physical inactivity (15·2% [12·8-17·7], p<0·0001), and obesity (9·4% [7·3-11·7], p<0·0001). According to weighted PAF values, low education (9·3% [6·9-11·7], p<0·0001), physical inactivity (7·3% [3·9-11·2], p=0·0021), hearing loss (7·2% [5·2-9·7], p<0·0001), hypertension (7·1% [5·4-8·8], p<0·0001), and obesity (5·3% [3·2-7·4], p=0·0001) had the highest pooled estimates. When low education, midlife hypertension, midlife obesity, smoking, physical inactivity, depression, and diabetes were combined (Barnes and Yaffe seven-factor model; n=9 studies), the pooled unweighted and weighted PAF values were 55·0% (46·5-63·5; p<0·0001) and 32·0% (26·6-37·5; p<0·0001), respectively. The pooled PAF values for most individual risk factors were higher in low-income and middle-income countries (LMICs) versus high-income countries. Governments need to invest in a life-course approach to dementia prevention, including policies that enable quality education, health-promoting environments, and improved health. This investment is particularly important in LMICs, where the potential for prevention is high, but resources, infrastructure, budgets, and research focused on ageing and dementia are limited. UK Research and Innovation (Medical Research Council).

Association between household size and risk of incident dementia in the UK Biobank study

Currently, the relationship between household size and incident dementia, along with the underlying neurobiological mechanisms, remains unclear. This prospective cohort study was based on UK Biobank participants aged ≥ 50 years without a history of dementia. The linear and non-linear longitudinal association was assessed using Cox proportional hazards regression and restricted cubic spline models. Additionally, the potential mechanisms driven by brain structures were investigated by linear regression models. We included 275,629 participants (mean age at baseline 60.45 years [SD 5.39]). Over a mean follow-up of 9.5 years, 6031 individuals developed all-cause dementia. Multivariable analyses revealed that smaller household size was associated with an increased risk of all-cause dementia (HR, 1.06; 95% CI 1.02–1.09), vascular dementia (HR, 1.08; 95% CI 1.01–1.15), and non-Alzheimer’s disease non-vascular dementia (HR, 1.09; 95% CI 1.03–1.14). No significant association was observed for Alzheimer’s disease. Restricted cubic splines demonstrated a reversed J-shaped relationship between household size and all-cause and cause-specific dementia. Additionally, substantial associations existed between household size and brain structures. Our findings suggest that small household size is a risk factor for dementia. Additionally, brain structural differences related to household size support these associations. Household size may thus be a potential modifiable risk factor for dementia.

Associations between housing and psychological damage by earthquake and modifiable risk factors for dementia in general older adults: Tohoku Medical Megabank community-based cohort study.

To evaluate the association between housing and psychological damage caused by the Great East Japan Earthquake (GEJE) and modifiable risk factors (MRFs) of dementia for general population of older adults. This cross-sectional study enrolled 29 039 community-dwelling older adults (mean age 69.1 ± 2.9 years, 55.5% women). We evaluated disaster-related damage (by complete or not complete housing damage) and psychological damage (by post-traumatic stress reaction [PTSR]) after the GEJE using a self-report questionnaire. MRFs encompassed the presence of depression, social isolation, physical inactivity, smoking, and diabetes. We examined the association between disaster-related damage and MRFs using ordinary least squares and modified Poisson regression models adjusted for sociodemographic and health status variables. Complete housing damage and PTSR were identified in 2704 (10.0%) and 855 (3.2%) individuals, respectively. The number of MRFs was significantly larger for the individuals with complete housing damage (β = 0.23; 95% confidence interval [CI]: 0.19-0.27) and PTSR (β = 0.60; 95% CI: 0.53-0.67). Prevalence ratios (PRs) for depression and physical inactivity were higher in individuals with complete housing damage. The PRs for all domains of the MRFs were significantly higher in individuals with PTSR. Housing and psychological damage caused by the GEJE were associated with an increased risk factor of dementia. To attenuate the risk of dementia, especially among older victims who have experienced housing and psychological damage after a disaster, multidimensional support across various aspects of MRFs is required. Geriatr Gerontol Int 2024; 24: 509-516.

Association of Family Support With Lower Modifiable Risk Factors for Dementia Among Cognitively Impaired Older Adults

ObjectivesCognitive impairment poses considerable challenges among older adults, with the role of family support becoming increasingly crucial. This study examines the association of children's residential proximity and spousal presence with key modifiable risk factors for dementia in cognitively impaired older adults. MethodsWe analyzed 14,600 individuals (35,165 observations) aged 50 and older with cognitive impairment from the Health and Retirement Study (1995–2018). Family support was categorized by spousal presence and children's residential proximity. Modifiable risk factors, including smoking, depressive symptoms, and social isolation, were assessed. Associations between family support and the modifiable risk factors were determined using mixed-effects logistic regressions. ResultsA significant proportion of older adults with cognitive impairment lacked access to family support, with either no spouse (46.9%) or all children living over 10 miles away (25.3%). Those with less available family support, characterized by distant-residing children and the absence of a spouse, had a significantly higher percentage of smoking, depressive symptoms, and social isolation. Moreover, we revealed a consistent gradient in the percentage of the risk factors by the degree of family support. Relative to older adults with a spouse and co-resident children, those without a spouse and with all children residing further than 10 miles displayed the highest percentage of the risk factors. These findings were robust to various sensitivity analyses. ConclusionsFamily support from spouses and nearby children serves as a protective factor against modifiable dementia risk factors in cognitively impaired older adults. Policies that strengthen family and social support may benefit this population.

Experimental laboratory models as tools for understanding modifiable dementia risk.

Experimental laboratory research has an important role to play in dementia prevention. Mechanisms underlying modifiable risk factors for dementia are promising targets for dementia prevention but are difficult to investigate in human populations due to technological constraints and confounds. Therefore, controlled laboratory experiments in models such as transgenic rodents, invertebrates and in vitro cultured cells are increasingly used to investigate dementia risk factors and test strategies which target them to prevent dementia. This review provides an overview of experimental research into 15 established and putative modifiable dementia risk factors: less early-life education, hearing loss, depression, social isolation, life stress, hypertension, obesity, diabetes, physical inactivity, heavy alcohol use, smoking, air pollution, anesthetic exposure, traumatic brain injury, and disordered sleep. It explores how experimental models have been, and can be, used to address questions about modifiable dementia risk and prevention that cannot readily be addressed in human studies. HIGHLIGHTS: Modifiable dementia risk factors are promising targets for dementia prevention. Interrogation of mechanisms underlying dementia risk is difficult in human populations. Studies using diverse experimental models are revealing modifiable dementia risk mechanisms. We review experimental research into 15 modifiable dementia risk factors. Laboratory science can contribute uniquely to dementia prevention.

The mediating role of neuroimaging-derived biological brain age in the association between risk factors for dementia and cognitive decline in middle-aged and older individuals without cognitive impairment: a cohort study

Neuroimaging-based brain-age delta has been shown to be a mediator linking cardiovascular risk factors to cognitive function. We aimed to assess the mediating role of brain-age delta in the association between modifiable risk factors of dementia and longitudinal cognitive decline in middle-aged and older individuals who are asymptomatic, stratified by Alzheimer's disease pathology. We also explored whether the mediation effect is specific to cognitive domain. In this cohort study, we included participants from the ALFA+ cohort aged between 45 years and 65 years who were cognitively unimpaired and who had available structural MRI, cerebrospinal fluid β-amyloid (Aβ)42 and Aβ40 measurements obtained within 1 year of each other, modifiable risk factors assessment, and cognitive evaluation over 3 years. Participants were recruited from the Barcelonaβeta Brain Research Center (Barcelona, Spain). Included individuals underwent a first assessment between Oct 25, 2016, and Jan 28, 2020, and a follow-up cognitive assessment 3·28 (SD 0·27) years later. We computed brain-age delta and composites of different cognitive function domains (preclinical Alzheimer's cognitive composite [PACC], attention, executive function, episodic memory, visual processing, and language). We used partial least squares path modelling to explore mediation effects in the associations between modifiable risk factors (including cardiovascular, mental health, mood, metabolic or endocrine history, and alcohol use) and changes in cognitive composites. To assess the role of Alzheimer's disease pathology, we computed separate models for Aβ-negative and Aβ-positive individuals. Of the 419 participants enrolled in ALFA+, 302 met our inclusion criteria, of which 108 participants were classified as Aβ-positive and 194 as Aβ-negative. In Aβ-positive individuals, brain-age delta partially mediated (percent mediation proportion 15·73% [95% CI 14·22-16·66]) the association between modifiable risk factors and decline in overall cognition (across cognitive domains). Brain-age delta fully mediated (mediation proportion 28·03% [26·25-29·21]) the effect of modifiable risk factors on the PACC, wherein increased values for risk factors correlated with an older brain-age delta, and, consequently, an older brain-age delta was linked to greater PACC decline. This effect appears to be primarily driven by memory decline. Mediation was not significant in Aβ-negative individuals (3·52% [0·072-4·17]) on PACC, although path coefficients were not significantly different from those in the Aβ-positive group. Our findings suggest that brain-age delta captures the association between modifiable risk factors and longitudinal cognitive decline in middle-aged and older people. In asymptomatic middle-aged and older individuals who are Aβ-positive, the pathology might be the strongest driver of cognitive decline, whereas the effect of risk factors is smaller. Our results highlight the potential of brain-age delta as an objective outcome measure for preventive lifestyle interventions targeting cognitive decline. La Caixa Foundation, the TriBEKa Imaging Platform, and the Universities and Research Secretariat of the Catalan Government. For the Spanish translation of the abstract see Supplementary Materials section.

Delirium and incident dementia in hospital patients in New South Wales, Australia: retrospective cohort study

ObjectivesTo determine the strength and nature of the association between delirium and incident dementia in a population of older adult patients without dementia at baseline.DesignRetrospective cohort study using large scale...

The effects of genetic and modifiable risk factors on brain regions vulnerable to ageing and disease

We have previously identified a network of higher-order brain regions particularly vulnerable to the ageing process, schizophrenia and Alzheimer’s disease. However, it remains unknown what the genetic influences on this fragile brain network are, and whether it can be altered by the most common modifiable risk factors for dementia. Here, in ~40,000 UK Biobank participants, we first show significant genome-wide associations between this brain network and seven genetic clusters implicated in cardiovascular deaths, schizophrenia, Alzheimer’s and Parkinson’s disease, and with the two antigens of the XG blood group located in the pseudoautosomal region of the sex chromosomes. We further reveal that the most deleterious modifiable risk factors for this vulnerable brain network are diabetes, nitrogen dioxide – a proxy for traffic-related air pollution – and alcohol intake frequency. The extent of these associations was uncovered by examining these modifiable risk factors in a single model to assess the unique contribution of each on the vulnerable brain network, above and beyond the dominating effects of age and sex. These results provide a comprehensive picture of the role played by genetic and modifiable risk factors on these fragile parts of the brain.

Abstract 46: Midlife and Late-Life Population Attributable Fractions of Dementia Risk Factors in the United States: A Cohort Study From the Dementia Risk Pooling Project

Introduction: Dementia cases in the US are projected to nearly double from 5.3 million in 2019 to 10.5 million by 2050. Research has suggested that 41% of US dementia cases may be prevented by eliminating several specific modifiable risk factors. Still, few studies examine risk factor variation between midlife and late-life. Previous studies have also been limited by sample diversity and size. The Dementia Risk Pooling Project (DRPP) is a consortium of longitudinal cohorts including several underrepresented racial/ethnic groups pooled at the individual level. Methods: We estimated individual and combined population attributable fractions (PAF) for seven modifiable risk factors in midlife (aged 45-64) and late-life (aged 65+), using data from six US cohorts in DRPP. We also used potential impact fractions (PIF) to estimate dementia cases that could be prevented due to risk factor reduction in midlife and late-life based upon the National Alzheimer’s Advisory Council goal of a 15% reduction in dementia risk factors by 2030. Results: In a sample of 41,432 unique participants (ppts), risk factor exposure was measured in midlife for 29,983 ppts (60% female, 77% white) and in late-life for 30,633 ppts (56% female, 70% white). During follow-up, 4,186 midlife ppts and 4,893 late-life ppts developed dementia. We found that eliminating midlife risk factors could prevent a greater proportion of dementia cases [PAF 41.3%, 27.9%-54.6%] compared to late-life risk factors [23.1%, 12.4%-33.7%]. Midlife physical inactivity [18.8%, 15.1%-22.4%] appeared to be the greatest contributor. Late-life hypertension and depression appeared to contribute to 9.8% [5.5%-13.9%] and 4.2% [3.5%-5.0%] of cases, respectively. Given the US prevalence of dementia in 2020, we estimate that a 15% reduction in physical inactivity alone could prevent 148,339 dementia cases. Conclusion: The importance of modifiable risk factors for dementia may vary with age. These estimates could inform the timing of public health interventions for dementia prevention.

Abstract P217: Directionality of Associations Between Daily Physical Activity and Cognition Among Older Adults in the Baltimore Longitudinal Study of Aging

Physical activity is a modifiable risk factor for dementia. Associations between physical activity and cognition are likely bidirectional, as cognitive functions are required to initiate and perform activities. Understanding the directionality of these associations has potential implications for both dementia prevention and physical activity engagement. Yet, the directionality between cognitive function and free-living physical activity patterns is unclear. This study included 237 cognitively unimpaired older adults in the BLSA with cognitive test performance and ≥ 3 valid days of wrist accelerometry measured at 2 visits over an average of 1.8 (0.9-4.0) years. Cognitive domain factor scores were derived using confirmatory factor analysis. Accelerometry data were used to calculate daily physical activity patterns: 1) total activity counts (TAC), 2) time spent active, 3) time spent non-active, 4) active-to-sedentary-transition probability (ASTP), 5) mean active bout length, 6) sedentary-to-active transition probability (SATP), 7) mean non-active bout length. Bivariate latent change score models estimated directionality of associations between changes in cognitive factor scores and changes in daily physical activity patterns. Models were adjusted for age, sex, race, education, and number of comorbidities. Participants were on average 77 (60-96) years, 48% women, and 22% Black. After covariate adjustment, one SD higher in baseline TAC was associated with less memory decline (estimate = 0.089, SE = 0.045). One SD higher in baseline time spent non-active was associated with greater declines in language (estimate = -0.068, SE = 0.035), visuospatial processing (estimate = -0.079 SE = 0.034), and global cognition (estimate = -0.058, SE = 0.024). One SD higher in baseline ASTP was associated with greater declines in memory (estimate = -0.114, SE = 0.047) and visuospatial processing (estimate = -0.074, SE = 0.034), whereas mean active bout length was associated with less decline in these domains (memory: estimate = 0.121, SE = 0.046; visuospatial processing: estimate = 0.081, SE = 0.033). There were no associations with time spent active, SATP, or mean non-active bout length and changes in any cognitive factor score. Cognitive factor scores were not associated with changes in any activity pattern. Patterns relating to amount of daily activity, time spent sedentary, and probability of transitioning from active-to-sedentary states were primarily associated with changes in memory and visuospatial processing. This suggests increasing free-living movement or decreasing sedentary behavior might be related to short-term changes in cognition among older adults. Future studies are needed to determine causality of these associations and to evaluate directionality over longer periods of time.

Cross-sectional associations between neighborhood characteristics, cognition and dementia risk factor burden in middle-aged and older Australians

Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition. This was a cross-sectional analysis of 2016–2020 data from the Healthy Brain Project, a population-based cohort of community-dwelling individuals across Australia. Participants were aged 40–70 and free of dementia. Measures included greenspace (greenspace % in the local area, and distance to greenspace, n = 2,181); and intersection density (n = 1,159), and crime (rate of recorded offences; n = 1,159). Outcomes included a modified Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) dementia risk score to index the burden of modifiable vascular dementia risk factors; and composite scores of both memory and attention, derived from the Cogstate Brief Battery. Linear regressions adjusted for age, sex, education, and personal socio-economic status, demonstrated distance to greenspace (b ± SE per 2-fold increase = 0.09 ± 0.03, p =.005) and crime rate (b ± SE per 2-fold increase = 0.07 ± 0.03, p =.018) were associated with higher modified CAIDE. Higher crime was associated with lower memory performance (b ± SE = -0.03 ± 0.01, p =.018). The association between distance to greenspace and modified CAIDE was only present in low-moderate socioeconomic status neighborhoods (p interaction = 0.004). Dementia prevention programs that address modifiable risk factors in midlife should consider the possible role of neighborhood characteristics.

Potentially modifiable risk factors for dementia in six low-income and middle-income countries: A multinational, population-based survey

ObjectivesWe aimed to determine the proportion of dementia cases potentially preventable in six low-income and middle-income countries. Study designWe analyzed data from 19,278 adults aged 50 years or more from China, South Africa, Ghana, India, Russia, and Mexico included in the WHO's Study on global AGEing and adult health. Main outcome measuresWe calculated the population attributable fraction for ten potentially modifiable risk factors: less education, hearing loss, hypertension, diabetes, depression, heavy drinking, obesity, smoking, physical inactivity, and social isolation. Weighted attributable fraction was calculated considering communality among risk factors. ResultsWe estimated that 37.6 % of the burden of dementia might be attributable to these risk factors. The highest and lowest overall weighted attributable fractions were 38.3 % and 22.9 % in China and Ghana, respectively. Less education (8.3 %), smoking (6.3 %), and physical inactivity (5.7 %) showed the highest attributable fraction for dementia. The overall attributable fraction was higher in the poorest (38.1 %) than in the richest (30.9 %) income quintile. The burden of obesity, diabetes, and hypertension was 61 % higher in the wealthiest than in the poorest population. A total of 7.2 million cases of dementia in these six low- and middle-income countries are potentially caused by these ten potentially modifiable risk factors. ConclusionsOverall, 38 % of cases of dementia in China, South Africa, Ghana, India, Russia, and Mexico can be attributable to ten potentially modifiable risk factors. Cardiometabolic risk factors account for a more significant burden of dementia in the wealthiest population. Less education had the highest population attributable fraction independent of living area and income.

Rural-urban disparities in the diagnosis and treatment of hypertension and diabetes among aging Indians.

Hypertension and diabetes are modifiable risk factors for dementia. We aimed to assess rural-urban disparities in the diagnosis and treatment of these conditions among aging Indians. Participants (n=6316) were from two parallel, prospective aging cohorts in rural and urban India. Using self-report and clinical/biochemical assessments, we subdivided participants with diabetes and hypertension into undiagnosed and untreated groups. Logistic regression and Fairlie decomposition analysis were the statistical methods utilized. There was a significant rural-urban disparity in undiagnosed hypertension (25.14%), untreated hypertension (11.75%), undiagnosed diabetes (16.94%), and untreated diabetes (11.62%). Further, sociodemographic and lifestyle factors, such as age and tobacco use were the common contributors to the disparities in both undiagnosed hypertension and undiagnosed diabetes, whereas education and body mass index (BMI) were significant contributors to the disparity in untreated hypertension. Rural Indians face significant healthcare disadvantages as compared to their urban counterparts, which prompts the urgent need for strategies for equitable healthcare.

Associations between multidomain modifiable dementia risk factors with AD biomarkers and cognition in middle-aged and older adults

This study aimed to determine associations between modifiable dementia risk factors (MDRF), across domains mood symptomatology, lifestyle behaviors, cardiovascular conditions, cognitive/social engagement, sleep disorders/symptomatology, with cognition, beta-amyloid (Aβ) and tau, and brain volume. Middle-aged/older adults (n=82) enrolled in a sub-study of the Healthy Brain Project completed self-report questionnaires and a neuropsychological battery. Cerebrospinal fluid levels of Aβ 1–42, total tau (t-tau), and phosphorylated tau (p-tau181) (Roche Elecsys), and MRI markers of hippocampal volume and total brain volume were obtained. Participants were classified as no/single domain risk (≤1 domains) or multidomain risk (≥2 domains). Compared to the no/single domain risk group, the multidomain risk group performed worse on the Preclinical Alzheimer’s Cognitive Composite (d=0.63, p=.005), and Executive Function (d=0.50, p=.016), and had increased p-tau181 (d=0.47, p=.042) and t-tau (d=0.54, p=.021). In middle-aged/older adults, multidomain MDRFs were related to increases in tau and worse cognition, but not Aβ or brain volume. Findings suggest that increases in AD biomarkers are apparent in midlife, particularly for individuals with greater burden, or variety of MDRFs.

Epilepsy and epileptiform activity in late-onset Alzheimer disease: clinical and pathophysiological advances, gaps and conundrums.

A growing body of evidence has demonstrated a link between Alzheimer disease (AD) and epilepsy. Late-onset epilepsy and epileptiform activity can precede cognitive deterioration in AD by years, and its presence has been shown to predict a faster disease course. In animal models of AD, amyloid and tau pathology are linked to cortical network hyperexcitability that precedes the first signs of memory decline. Thus, detection of epileptiform activity in AD has substantial clinical importance as a potential novel modifiable risk factor for dementia. In this Review, we summarize the epidemiological evidence for the complex bidirectional relationship between AD and epilepsy, examine the effect of epileptiform activity and seizures on cognition in people with AD, and discuss the precision medicine treatment strategies based on the latest research in human and animal models. Finally, we outline some of the unresolved questions of the field that should be addressed by rigorous research, including whether particular clinicopathological subtypes of AD have a stronger association with epilepsy, and the sequence of events between epileptiform activity and amyloid and tau pathology.

Modifiable dementia risk factors and AT(N) biomarkers: findings from the EPAD cohort.

Modifiable risk factors account for a substantial proportion of Alzheimer's disease (AD) cases and we currently have a discrete AT(N) biomarker profile for AD biomarkers: amyloid (A), p-tau (T), and neurodegeneration (N). Here, we investigated how modifiable risk factors relate to the three hallmark AT(N) biomarkers of AD. Participants from the European Prevention of Alzheimer's Dementia (EPAD) study underwent clinical assessments, brain magnetic resonance imaging, and cerebrospinal fluid collection and analysis. Generalized additive models (GAMs) with penalized regression splines were modeled in the AD Workbench on the NTKApp. A total of 1,434 participants were included (56% women, 39% APOE ε4+) with an average age of 65.5 (± 7.2) years. We found that modifiable risk factors of less education (t = 3.9, p < 0.001), less exercise (t = 2.1, p = 0.034), traumatic brain injury (t = -2.1, p = 0.036), and higher body mass index (t = -4.5, p < 0.001) were all significantly associated with higher AD biomarker burden. This cross-sectional study provides further support for modifiable risk factors displaying neuroprotective associations with the characteristic AT(N) biomarkers of AD.

ENHANCE: a comparative prospective longitudinal study of cognitive outcomes after 3 years of hearing aid use in older adults.

With an aging population, the prevalence of hearing loss and dementia are increasing rapidly. Hearing loss is currently considered the largest potentially modifiable risk factor for dementia. The effect of hearing interventions on cognitive function should therefore be investigated, as if effective, these may be successfully implemented to modify cognitive outcomes for older adults with hearing loss. This prospective longitudinal observational cohort study compared outcomes of a convenience sample of prospectively recruited first-time hearing aid users without dementia from an audiology center with those of community-living older adults participating in a large prospective longitudinal cohort study with/without hearing loss and/or hearing aids. All participants were assessed at baseline, 18 months, and 36 months using the same measures. Participants were 160 audiology clinic patients (48.8% female patient; mean age 73.5 years) with mild-severe hearing loss, fitted with hearing aids at baseline, and 102 participants of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Aging (AIBL) (55.9% female patient; mean age 74.5 years). 18- and 36-month outcomes of subsets of the first participants to reach these points and complete the cognition assessment to date are compared. Primary comparative analysis showed cognitive stability for the hearing aid group while the AIBL group declined on working memory, visual attention, and psychomotor function. There was a non-significant trend for decline in visual learning for the AIBL group versus no decline for the hearing aid group. The hearing aid group showed significant decline on only 1 subtest and at a significantly slower rate than for the AIBL participants (p < 0.05). When education effects on cognitive trajectory were controlled, the HA group still performed significantly better on visual attention and psychomotor function (lower educated participants only) compared to the AIBL group but not on working memory or visual learning. Physical activity had no effect on cognitive performance trajectory. Hearing aid users demonstrated significantly better cognitive performance to 3 years post-fitting, suggesting that hearing intervention may delay cognitive decline/dementia onset in older adults. Further studies using appropriate measures of cognition, hearing, and device use, with longer follow-up, are required.

1955 Multimodal critical discourse analysis of current representations of hearing loss in the UK news media

Abstract Introduction Hearing loss (HL) affects 12 million UK adults, including 70% of those aged over 70 years. It is associated with social isolation, anxiety, and depression. Furthermore, HL in midlife is the largest modifiable risk factor for dementia. However, many individuals delay or avoid treatment. This may be due to limited understanding of HL amongst the public, and the considerable stigma surrounding HL and hearing aids. The media play a crucial role in shaping public perceptions of age-related conditions. Therefore, this study investigated representations of HL in UK newspapers, especially representations of the relationship between HL and mental health. Method Using Nexis (a news database), 7173 newspaper articles featuring HL between May 2022-May 2023 were retrieved. Following screening, 20 articles were analysed using multimodal critical discourse analysis. This qualitative approach regards communicative choices (here, images and text) as able to both reflect and shape society, including propagating or challenging stigma. A Patient and Public Involvement (PPI) panel contributed to study design and data interpretation. Results Most articles featured young adults with HL, particularly celebrities. Whilst this could challenge the stereotype that HL only affects older adults, it could also increase the invisibility of older adults in the media. Many articles contained inspirational stories, which may help reduce the stigma of HL. However, some people with HL do not want to be portrayed differently to other people. Some articles discussed HL and mental health, especially its association with dementia, loneliness, and depression. PPI contributors indicated that newspapers should provide diverse HL representations and should help improve public awareness of this condition, especially its impact on mental health. Discussion This research has important implications for clinicians, researchers, charities, the media, and all those who communicate with the public about HL. Future research should investigate HL representations in other media, particularly social media.