Potential Risk Factor For Dementia Research Articles

The longitudinal associations between ambient air pollution exposure and dementia in the UK: results from the cognitive function and ageing study II and Wales

BackgroundAir pollution has been recognised as a potential risk factor for dementia. Yet recent epidemiological research shows mixed evidence. The aim of this study is to investigate the longitudinal associations between ambient air pollution exposure and dementia in older people across five urban and rural areas in the UK.MethodsThis study was based on two population-based cohort studies of 11329 people aged ≥ 65 in the Cognitive Function and Ageing Study II (2008–2011) and Wales (2011–2013). An algorithmic diagnosis method was used to identify dementia cases. Annual concentrations of four air pollutants (NO2, O3, PM10, PM2.5) were modelled for the year 2012 and linked via the participants’ postcodes. Multistate modelling was used to examine the effects of exposure to air pollutants on incident dementia incorporating death and adjusting for sociodemographic factors and area deprivation. A random-effect meta-analysis was carried out to summarise results from the current and nine existing cohort studies.ResultsHigher exposure levels of NO2 (HR: 1.04; 95% CI: 0.94, 1.14), O3 (HR: 0.90; 95% CI: 0.70, 1.15), PM10 (HR: 1.17; 95% CI: 0.86, 1.58), PM2.5 (HR: 1.41; 95% CI: 0.71, 2.79) were not strongly associated with dementia in the two UK-based cohorts. Inconsistent directions and strengths of the associations were observed across the two cohorts, five areas, and nine existing studies.ConclusionsIn contrast to the literature, this study did not find clear associations between air pollution and dementia. Future research needs to investigate how methodological and contextual factors can affect evidence in this field and clarity the influence of air pollution exposure on cognitive health over the lifecourse.

Weight change in people with depression and the risk of dementia: a nationwide cohort study.

Depression is a risk factor for dementia and weight change can appear as a symptom of depression. However, the association between weight change after the diagnosis of depression and the risk of dementia is poorly established. This study aimed to investigate the association between weight change before and after a diagnosis of depression with the subsequent risk of dementia. The National Health Insurance Sharing Service database was used. 1 308 730 patients aged ⩾40 years diagnosed with depression were identified to be eligible. Weight changes after their depression diagnosis were categorized and subsequent incidence of dementia was followed up. During an average follow-up period of 5.2 years (s.d., 2.0 years), 69 373 subjects were newly diagnosed with all-cause dementia (56 351 were Alzheimer's disease and 6877 were vascular dementia). Regarding all outcomes, compared to those with a minimal weight change (-5 to 5%), all groups with weight gain or loss showed increased risks of dementia after adjusting potential risk factors for dementia, in all analysis models with a dose-response relationship, showing a U-shaped association. Weight change as a symptom of depression could be a predictor for the future development of dementia.

SOCIAL ISOLATION AND RISK OF DEMENTIA: DO RACE, ETHNICITY, AND GENDER MATTER?

Abstract Social isolation has emerged as a significant predictor of dementia risk in later life. However, our understanding of how this association may vary across race-ethnicity and gender remains limited. To address this gap, we used longitudinal data from the Health and Retirement Study (2000-2016) to examine the link between social isolation and dementia risk among older adults, separately for non-Hispanic Whites, non-Hispanic Blacks, and Hispanics. We also explored gender variations in this association within each racial-ethnic group. Our results indicate that social isolation increases the risk of dementia for both non-Hispanic Whites and Blacks, even after controlling for basic sociodemographic characteristics. However, social isolation does not appear to be a significant predictor of dementia risk among Hispanics, suggesting that cultural and social factors may play a key role in the association between social isolation and dementia risk across racial/ethnic groups. Further, we found few significant gender variations in the association between social isolation and dementia, except for a stronger effect of severe isolation among Black men compared to Black women. Economic resources and health-related factors were identified as significant mediators of the relationship between social isolation and dementia risk for both non-Hispanic Whites and Blacks. Our study highlights the importance of addressing social isolation as a potential risk factor for dementia among older adults, particularly for those in vulnerable groups. The findings underscore the need for targeted interventions to reduce social isolation and promote social engagement in diverse communities to mitigate dementia risk.

Association between periodontitis treatment and dementia in Taiwanese adults

BackgroundThe chronic systemic inflammatory response in periodontitis may be a potential risk factor for dementia, especially in adults. This study determined the association between periodontal treatment and dementia in adults and evaluated the effect of regular scaling treatment on the risk of dementia in this population.MethodsThis case–control study identified 18,930 patients with a dementia-related diagnosis from the Taiwan National Health Insurance Research Database. Scaling and periodontal emergency treatments were evaluated after 1 year and 3 years. Using multivariable logistic regression analysis to evaluate the association between periodontal emergency treatment and dementia risk.ResultsThe results showed that scaling treatment rates were lower in the dementia cohort than the non-dementia cohort after 1 and 3 years. Patients who received periodontal emergency treatment within 3 years had a significantly increased risk of dementia. Furthermore, patients with periodontitis who did not receive scaling treatment within 3 years had a higher risk of dementia than patients without periodontitis (OR, 1.22; 95% CI, 1.10–1.35).ConclusionThis study demonstrated that periodontitis and dementia are associated, and that periodontitis is a risk factor for dementia in adults. The risk of dementia was dependent on the periodontal health status of adults, and our findings suggest that regular scaling can reduce the incidence of dementia in adults. Therefore, regular and routine scaling treatment is suggested for adults.

Incidence and risk of dementia in people with Anxiety over 50 years old – an electronic health records study

AbstractBackgroundDepression is a well‐established risk factor for dementia, but we know far less about the links between Anxiety and future dementia risk in older people. The aim was therefore to investigate the incidence of dementia in people with and without Anxiety above the age of 50 years over a 10‐year period.MethodThe Health Improvement Network (THIN) was used, a large UK primary care dataset, that includes approximately 15.6 million patients, which is representative of the UK population. All people between 1st January 2008 and 31 December 2018 who had new onset Anxiety over the age of 50 years were identified. At the time of the first record of Anxiety, each person was individually matched to 4 unexposed persons based on their sex and age and Exposure Density Sampling was used, creating a dynamic cohort. Weibull survival regression models were fitted and hazard ratios (HR) were estimated for modelling time‐to‐dementia in those with and without Anxiety; and when determining the risk of developing dementia in those with Anxiety. Hazard ratio estimates were adjusted for sociodemographic and lifestyle factors, and relevant physical and mental health conditions.ResultIn this cohort study, there were 37,824 men and 68,761 women diagnosed with a first episode of Anxiety. Of those who had Anxiety, 2,792 people developed dementia during the follow up period, compared to 19,000 people in the non‐Anxiety group. The incidence of dementia in those with and without Anxiety was 7.21 (95% CI 6.94‐7.48) and 3.22 (95% CI 3.18‐3.28) respectively per 1,000 person‐years. The risk of dementia was increased 2.47‐fold [HR 2.47 (CI 2.37‐ 2.57)] in the Anxiety group when compared to the non‐Anxiety group after adjustment for age, sex, social deprivation, alcohol, smoking, BMI, diabetes mellitus, cardiovascular diseases, learning disabilities, HIV, multiple sclerosis, brain injury and hearing impairment.ConclusionThe incidence of dementia was greater in those with Anxiety and the risk of developing dementia was more than doubled in people with Anxiety compared to those without. This provides further evidence that Anxiety is a potential risk factor for dementia.

SLEEP MICROARCHITECTURE IN MILD COGNITIVE IMPAIRMENT: A HIGH‐DENSITY EEG STUDY

AbstractBackgroundSleep disturbance and sleep disorders are potential risk factors for dementia. Adults with mild cognitive impairment (MCI) are at increased risk of developing dementia and many report disturbed sleep. Altered sleep neurophysiology including deficits in sleep spindles and slow wave activity (SWA) during NREM sleep have been reported in MCI, though studies are sparse. These NREM EEG oscillations are crucial for overnight memory consolidation and optimal daytime functioning. Abnormal EEG activity during sleep in MCI may adversely impact sleep‐dependent memory processes and cognitive trajectory. This study is the first to examine sleep microarchitecture using high‐density EEG technology in MCI.MethodOlder adults with multi‐domain MCI (n = 19, mean age 68.5 years) and cognitively‐intact controls (n = 22, 69 years) had 256‐channel high‐density EEG recordings during overnight polysomnography and resting wakefulness. Declarative (word paired associates) and procedural (finger tapping) memory tasks were administered before and after sleep. Neuropsychological testing and brain MRI scans were also performed. After artefact processing, spectral analysis was performed for high‐density EEG recordings. Topographical power maps were calculated for standard frequency ranges for NREM sleep (N2 and N3 (slow wave sleep)). Maps were compared between groups using normalized power (z‐scores computed for each subject).ResultThe MCI group had worse declarative (% retention, MCI vs Controls: 84.2 ± 16.6 vs. 94.5 ± 7.8, p = 0.024) and procedural (% early improvement: 92.9 ± 11.0 vs. 103.0 ± 12.0%, p = 0.017) overnight memory consolidation than the controls. Topographic analysis of high‐density EEG data revealed a regional increase in SWA (1‐4.5Hz) EEG power during N3 in a cluster of 18 electrodes overlying the centroparietal cortex in the MCI group (cluster mean t‐value = 3.11, p = 0.0036, uncorrected) and a regional reduction in SWA in the left frontal (5 channels, t = ‐3.75, p<0.001) and right temporal areas (5 channels, t = ‐3.46, p = 0.001), Figure 1.ConclusionOvernight memory consolidation was impaired in this MCI population. Regional differences in SWA during deep sleep were present in distinct brain regions and may indicate pathology. Future analysis exploring associations between EEG abnormalities with underlying brain structures may provide mechanistic insights into the impact of altered sleep neurophysiology on cognitive outcomes in MCI.

1 Subjective Cognitive Concerns, Neuropsychological Test Performances, and Frontoparietal Thickness and Connectivity in High-Functioning Older Adults

Objective:Neuropsychologists have difficulty detecting cognitive decline in high-functioning older adults, in whom substantially greater neurological change may need to occur before performance on cognitive tests are low enough to indicate cognitive impairment. For high-functioning older adults, subjective cognitive concerns (SCC) may indicate decline that is not detected by the presence of low cognitive test scores but may be related to the absence of high scores and the presence of latent neurological changes. We hypothesized that high-functioning older adults with SCC would have fewer high scores than those without concerns, but a comparable number of low scores. These findings would indicate that objective decline has occurred but would not be detected by a traditional focus on low scores. We also hypothesized that SCC would be associated with lower frontoparietal network volume, thickness, and connectivity, indicating latent neurological change underlying subjective cognitive concerns.Participants and Methods:Participants from an imaging sub-study of an ongoing longitudinal aging study were selected if they had high estimated premorbid functioning, defined as either (a) estimated intelligence >75th percentile on the North American Adult Reading Test (n=48) or (b) having a college degree (n=62). This resulted in 68 participants subdivided based on SCC, defined as one or more self-reported SCC on the Medical Outcomes Study Cognitive Functioning Scale (MOS-Cog). Participants with SCC (n=35; 73.9 years-old, SD=9.6, range: 60-95; 62.9% female; 94.3% White) and without SCC (n=33; 71.0 years-old, SD=7.2, range: 61-85, 75.8% female; 100% White) completed a neuropsychological test battery of memory and executive functions, including the Rey Auditory Verbal Learning Test, Trail Making Test Parts A and B, Controlled Oral Word Association Test, Digit Span, and Letter-Number Sequencing, and underwent structural MRI. MR images were analyzed for frontoparietal network volume, thickness, and connectivity.Results:Participants with and without SCC were compared on the number of low test scores (i.e., at or below the 16th percentile) and high test scores (i.e., at or above the 75th percentile), finding a comparable number of low scores, t=1.66, p=.103, d=.40, but a lower number of high scores among participants with SCC, t=2.95, p=.004, d=.71. Participants with SCC had lower bilateral mean frontoparietal network volumes (left: t=2.98, p=.004, d=.74; right: t=2.63, p=.011, d=.66) and cortical thickness (left: t=2.65, p=.010, d=.66; right: t=2.18, p=.033, d=.54), but did not differ from those without SCC in terms of network connectivity.Conclusions:SCC have been reported as a potential risk factor for dementia in older adults. High-functioning older adults with SCC presented with fewer high scores than those without SCC but had a comparable number of low scores. Among high-functioning older adults, subjective cognitive decline may correspond with objective cognitive change not detected by the traditional emphasis on low scores, but rather the absence of high scores. SCC were also related to underlying changes in the volume and thickness of the frontoparietal network, but not connectivity. In high-functioning older adults, subjective cognitive decline may correspond with a reduction from high average functioning in some domains and underlying neurological changes.

Sarcopenia using muscle mass prediction model and cognitive impairment: A longitudinal analysis from the English longitudinal study on ageing

BackgroundLiterature on the association between sarcopenia and cognitive impairment is largely unclear and mainly limited to non-European populations. Therefore, the aim of this study is to explore if the presence of sarcopenia at the baseline could increase the risk of cognitive impairment in a large cohort of older people participating to the English Longitudinal Study of Ageing (ELSA), over ten years of follow-up. MethodsSarcopenia was diagnosed as having low handgrip strength and low skeletal muscle mass index at the baseline, using a muscle mass prediction model; cognitive function was evaluated in the ELSA through several tests. The results are reported in the whole sample adjusted for potential baseline confounders and after matching sarcopenic and non-sarcopenic participants with a propensity score. Results2738 people (mean age: 68.7 years, 54.4% males) were included. During the ten years of follow-up, sarcopenia was associated with significantly lower scores in memory (p < 0.001), verbal fluency (p < 0.001), immediate word recall (p <0.001), delayed word recall (p = 0.018), and in recall summary score (p < 0.001). After adjusting for eight potential confounders, the presence of sarcopenia was significantly associated with poor verbal fluency (odds ratio, OR= 1.417, 95% confidence intervals, CI= 1.181–1.700) and in propensity-score matched analyses (OR=1.272, 95%CI= 1.071- 1.511). Conclusions and implicationsSarcopenia was found to be associated with a significantly higher incidence of poor cognitive status in a large population of elderly people followed up for 10 years, suggesting it may be an important potential risk factor for dementia.

0727 Association of sleep quality with memory functions among dementia-free, middle- and older-age, rural Indians

Abstract Introduction Sleep is known to be involved in cognitive processes, such as memory consolidation. Poor sleep is a potential risk factor for dementia. However, whether it is associated with decreased memory functions among dementia-free individuals is not well known. This study aims to investigate the effect of sleep quality on memory functions among middle and older-age adults from a rural Indian population. Methods Participants were dementia-free, rural Indians (≥ 45 years) recruited as part of an ongoing, prospective, aging cohort study, namely Srinivaspura Aging, NeuroSenescence, and COGnition (SANSCOG) study. Cross-sectional (baseline) data on sleep quality was obtained using Pittsburgh Sleep Quality Index (PSQI). Memory functions (at baseline) were assessed using subtests, namely immediate recall, delayed recall, name-face association, semantic fluency, phonemic fluency, and semantic association, from a culturally validated computerized neurocognitive test battery. Clinical Dementia Rating (CDR) was used to classify subjects based on their cognitive status into cognitively healthy (CDR=0) and MCI (CDR=0.5). Linear regression models, unadjusted and adjusted with cognitive status, age, gender, and depression, were used for analysis. Results In the unadjusted linear regression model 1, we found no association between sleep quality and the different subtests of memory. However, in model 2 (adjusting for cognitive status), sleep quality in persons with MCI was significantly associated with memory functions. Model 3 (model 2 + age) found that sleep quality in higher ages in MCI explained a significant variance in the association between sleep and subtests of memory function compared to cognitively healthy individuals. Model 4 (model 3 + gender) suggested that with increasing age, gender was significantly associated with sleep quality and memory among individuals with MCI compared to cognitively healthy individuals. Further, model 5 (model 4+ depression) found that depressed individuals with MCI showed a significant association between sleep quality and memory functions compared to those without depression. Conclusion When adjusted for cognitive status, age, gender and depression, there was significant association of sleep quality and memory functions, pointing to the important role of sleep in memory functions among middle and older-aged individuals without dementia. Support (if any) SANSCOG study is funded through the Centre for Brain Research by Pratiksha Trust

Spinal cord injury-activated C/EBPβ-AEP axis mediates cognitive impairment through APP C586/Tau N368 fragments spreading

Spinal cord injury (SCI) leads to mental abnormalities such as dementia and depression; however, the molecular mechanism of SCI-induced dementia remains a matter of debate. Asparagine endopeptidase (AEP) mediated dementia by enhancing amyloid plaque and Tau hyperphosphorylation, indicating that it played an important role in neurodegeneration. Here we revealed that SCI stimulated AEP activation in mice with T9 contusion injury. Activated-AEP cleaved APP and Tau, resulting in APP C586 and Tau N368 formations, and consequentially accelerated Aβ deposit and Tau hyperphosphorylation, respectively. At 9 months following injury, mice demonstrated a severe deterioration in cognitive-behavioral function, which was corroborated by the presence of accumulated AD-specific pathologies. Surprisingly, activated AEP was found in the brains of mice with spinal cord injury. In contrast, AEP knockout reduced SCI-induced neuronal death and neuroinflammation, resulting in cognitive-behavioral restoration. Interestingly, compared to the full-length proteins, truncated Tau N368 and APP C586 were easier to bind to each other. These AEP-processed fragments can not only be induced to pre-formed fibrils, but also amplified their abilities of spreading and neurotoxicity in vitro. Furthermore, as a critical transcription factor of AEP, C/EBPβ was activated in injured spinal cord. Elevated C/EBPβ level, as well as microglia population and inflammatory cytokines were also noticed in the cortex and hippocampus of SCI mice. These neuroinflammation pathologies were close related to the amount of Tau N368 and APP C586 in brain. Moreover, administration with the AEP-specific inhibitor, compound #11, was shown to decelerate Aβ accumulation, tauopathy and C/EBPβ level in both spinal cord and brain of SCI mice. Thus, this study highlights the fact that spinal cord injury is a potential risk factor for dementia, as well as the possibility that C/EBPβ-AEP axis may play a role in SCI-induced cognitive impairment.

Air Pollution: A Silent Key Driver of Dementia.

In 2017, the Lancet Commission on Dementia Prevention, Intervention, and Care included air pollution in its list of potential risk factors for dementia; in 2018, the Lancet Commission on Pollution concluded that the evidence for a causal relationship between fine particulate matter (PM) and dementia is encouraging. However, few interventions exist to delay or prevent the onset of dementia. Air quality data are becoming increasingly available, and the science underlying the associated health effects is also evolving rapidly. Recent interest in this area has led to the publication of population-based cohort studies, but these studies have used different approaches to identify cases of dementia. The purpose of this article is to review recent evidence describing the association between exposure to air pollution and dementia with special emphasis on fine particulate matter of 2.5 microns or less. We also summarize here the proposed detailed mechanisms by which air pollutants reach the brain and activate the innate immune response. In addition, the article also provides a short overview of existing limitations in the treatment of dementia.

Relative importance of potential risk factors for dementia in patients with hypertension.

Patients with hypertension are at higher risk for dementia than the general population. We sought to understand the relative importance of various risk factors in the development of dementia among patients with hypertension. This population-based cohort study used data from the Korean National Insurance Service database. Using the Cox proportional hazard model, R2 values for each potential risk factor were calculated to test the relative importance of risk factors for the development of dementia. Eligible individuals were adults 40 to 79 years of age with hypertension and without a history of stroke and dementia between 2007 and 2009. A total of 650,476 individuals (mean age, 60 ± 11 years) with hypertension were included in the analyses. During a mean follow-up of 9.5 years (±2.8 years), 57,112 cases of dementia were observed. The three strongest predictors of dementia were age, comorbidity burden (assessed using the Charlson Comorbidity Index), and female sex (R2 values, 0.0504, 0.0023, and 0.0022, respectively). The next strongest risk factors were physical inactivity, smoking, alcohol consumption, and obesity (R2 values, 0.00070, 0.00024, 0.00021, and 0.00020, respectively). Across all age groups, physical inactivity was an important risk factor for dementia occurrence. In summary, controlling and preventing comorbidities are of utmost importance to prevent dementia in patients with hypertension. More efforts should be taken to encourage physical activity among patients with hypertension across all age groups. Furthermore, smoking cessation, avoiding and limiting alcohol consumption, and maintaining an appropriate body weight are urged to prevent dementia.

Obstructive Sleep Apnoea (OSA) as a potentially modifiable risk factor for Mild Cognitive Impairment (MCI): A role for old age psychology?

It is estimated that just under a third of people with mild cognitive impairment (MCI) also have obstructive sleep apnoea (OSA; a form of sleep disordered breathing distinguished by repeated upper airway collapse during sleep), and disordered sleep is a potential risk factor for dementia. In this paper, we consider the potential role for the old age psychologist in (1) identifying OSA for onward referral and treatment, (2) assessing neurocognitive profiles in people with comorbid OSA and cognitive decline, (3) providing behavioural interventions to improve OSA treatment adherence, and (4) providing health psychology (lifestyle change) interventions relevant to both MCI and OSA.

Chronic alcohol metabolism results in DNA repair infidelity and cell cycle-induced senescence in neurons.

Chronic binge-like drinking is a risk factor for age-related dementia, however, the lasting and irreversible effect of alcohol on the brain remains elusive. Transcriptomic changes in brain cortices revealed pro-ageing hallmarks upon chronic ethanol exposure and these changes predominantly occur in neurons. The changes are attributed to a prioritized ethyl alcohol oxidation in these cells via the NADPH-dependent cytochrome pathway. This hijacks the folate metabolism of the 1-carbon network which supports the pathway choice of DNA repair via the non-cell cycle-dependent mismatch repair networks. The lost-in-function of such results in the de-inactivation of the less preferred cell cycle-dependent homologous recombination (HR) repair, forcing these post-mitotic cells to re-engage in a cell cycle-like process. However, mature neurons are post-mitotic. Therefore, instead of successfully completing a full round of cell cycle which is necessary for the completion of HR-mediated repair; these cells are arrested at checkpoints. The resulting persistence of repair intermediates induces and promotes the nuclear accumulation of p21 and cyclin B-a trigger for permanent cell cycle exits and irreversible senescence response. Supplementation of bioactive 5-methyl tetrahydrofolate simultaneously at times with ethyl alcohol exposure supports the fidelity of the 1-carbon network and hence the activity of the mismatch repair. This prevents aberrant and irreversible cell cycle re-entry and senescence events of neurons. Together, our findings offer a direct connection between binge-drinking behaviour and its irreversible impact on the brain, which makes it a potential risk factor for dementia.

Mendelian randomization study on the causal effect of chickenpox on dementia.

Some viruses, such as varicella zoster virus, are associated with severe dementia. The present study aims to identify the causal link between chickenpox and dementia. To date, the largest publicly available genome-wide association study (GWAS) for chickenpox (710 cases and 211 856 controls from European individuals) and for dementia (5933 cases and 212 859 controls from European individuals) were used to performed this two-sample Mendelian randomization (MR) study. We found no significant pleiotropy or heterogeneity in all seven selected chickenpox genetic instrumental variants in dementia GWAS. Of seven chickenpox genetic variants, two are located in the intergenic region and five are located in intron. We found that as chickenpox genetically increased, dementia risk increased based on an inverse-variance weightedanalysis (β = 0.070, 95% confidence interval [CI] for β: 0.014-0.126; odds ratio [OR] = 1.073, 95% CI for OR: 1.015-1.134; p = 0.014) and weighted median (β = 0.071, 95% CI for β: 0.002-0.141; OR = 1.074, 95% CI for OR: 1.002-1.152; p = 0.045). Reverse MR analysis showed no causal effect of dementia on chickenpox. Our analysis suggests a causal effect of genetically increased chickenpox on dementia risk. Thus, chickenpox may be a potential risk factor for dementia.

Associations of ischemic heart disease with dementia and cognitive decline in older adults: Results from a 12‐year population‐based cohort study

AbstractBackgroundIschemic heart disease (IHD) is a leading cause of death worldwide and a potential risk factor for dementia. However, the association of IHD with dementia and cognitive decline in old age has not been extensively addressed in population‐based cohorts. Furthermore, the extent to which the potential association of IHD with cognitive decline might be attributable to common complications of IHD, such as heart failure (HF) and atrial fibrillation (AF), remains unclear. The objective of this study is to investigate the longitudinal association of IHD with dementia and cognitive decline, and to clarify the role of HF and AF.MethodWe analysed data from 2615 dementia‐free participants in the population‐based Swedish National study on Aging and Care in Kungsholmen (age ≥ 60years, female 62%). Participants were regularly followed from 2001‐2004 (baseline) through 2013‐2016. IHD, HF, and AF cases until baseline were identified through patient registers, physical and instrumental examinations, and interviews by physicians. Dementia was diagnosed according to the DSM‐IV criteria. Global cognitive function was assessed with a neuropsychological test battery.The associations of IHD with incident dementia and cognitive decline were investigated using Cox proportional hazard models and linear mixed‐effects models, respectively. The models were controlled for age, sex, education, smoking, alcohol consumption, physical activity, vascular risk factors, and concomitant cardiovasulcar diseases (AF, HF, and stroke). Furthermore, we performed the stratified analysis by the presence of AF or HF.ResultDuring the 12‐year follow‐up period, 400 participants (15%) developed dementia. The multi‐adusted hazard ratio (HR) of dementia associated with prevalent IHD was 1.34 (95% CI: 1.03, 1.75) compared to those without IHD. This association remained significant in IHD without prevalent AF or HF at baseline. Similarly, prevalent IHD was associated with an average annual change in global cognitive z‐score of ‐0.02 (95% CI: ‐0.03, ‐0.01). The associations remained significant after excluding individuals with AF and HF. There was no statistical interaction of IHD with age, sex, or APOE genotype on risk of dementia and cognitive decline.ConclusionIHD is a risk factor for dementia and cognitive decline in the general older population independent of HF and AF.

0273 Sleep Disorders as a Potential Risk Factor for Dementia in Elderly Adults

Abstract Introduction Sleep disorders such as insomnia are seen in the early onset of Alzheimer’s disease, the most common form of dementia. Simultaneously, sleep disorders may indicate increased risk for the development of dementia. Due to the rate of comorbidity of these two conditions seen in the elderly population, the relationship between dementia and sleep disorders is a topic of interest for researchers. A bidirectional correlation between the two could have important implications in the clinical field exploring factors that lead to dementia Methods Data was assessed from 17,146 older adults from the 2018 Health and Retirement Survey. Participants were surveyed using questionnaires regarding both incident dementia or serious memory impairment in the past 2 years and the presence of a sleep disorder, as diagnosed by a doctor or health professional. Those who reported no dementia in the previous wave (N=16,547) were asked if they had been diagnosed since they were last asked. N=185 individuals reported incident dementia in the 2-years between assessments. Responses were coded to either “Yes” or “No”. A Poisson regression analysis was conducted to explore the relationship between incident dementia and sleep disorders. Results In a sample of older adults, unadjusted results indicate that having a sleep disorder was associated with a 0.6% increased risk of new onset dementia (PRR=1.006; 95%CI[1.001,1.012]; p=0.026). These results were sustained when adjusted for sex, age, race, ethnicity, and depression (PRR=1.006; 95%CI[1.001,1.012]; p=0.013). Conclusion Chronic sleep disturbances may be a factor used to indicate increased risk for dementia and help with early detection of the disease. These results demonstrate the value of sleep disorders screening among those at risk for dementia. Further research is needed to clarify these findings (e.g., explore specific sleep disorders) and expand the follow-up window (i.e., beyond 2 years). Support (If Any) The HRS (Health and Retirement Study) is sponsored by the National Institute on Aging (grant number NIA U01AG009740) and is conducted by the University of Michigan.

Physical Activity in Late Middle- to Older-Aged People and Dementia, Cognitive, and Physical Function Two Decades Later

Introduction: Low physical activity (PA) is a potential risk factor for dementia and cognitive impairment. However, few studies have focused on very old people (aged ≥80 years), the age group with highest prevalence of dementia. The aim was to investigate if PA associated with subsequent dementia, cognitive function, and gait speed (GS), in very old people. Methods: A population-based survey was conducted in 1999 and followed-up between 2016 and 2019 in participants ≥80 years. Altogether 541 individuals (56.2% women), 64.9 ± 4.2 years of age at baseline participated. Self-rated baseline PA was categorized into low, medium, or high. Cognitive function was assessed with the Mini-Mental State Examination (MMSE), executive function with the Frontal Assessment Battery (FAB), and GS (in meters/second) was measured over 2.4 m at follow-up. Results: During a mean of 19.0 ± 1.1 years, 175 (32.3%) developed dementia. Low or medium PA compared to high PA did not associate with subsequent dementia, and PA did not associate with future cognitive function (MMSE). PA associated with executive function (FAB) (unstandardized beta [95% confidence interval]) (0.67 [0.07–1.27]), but not after adjustments. PA associated with subsequent GS in the unadjusted model and after adjustment for age, sex, smoking, and education (0.06 [0.02–0.09], and 0.04 [0.01–0.08], respectively), but not after adding adjustment for hypertension, obesity, and glucose intolerance. Conclusion: No support was found for the hypothesis that low PA is a potential risk factor for dementia in very high age. However, PA and executive function were associated in unadjusted analyses which indicate that PA may be important for at least one aspect of cognitive function. The association between PA and GS around 2 decades later seems attenuated by cardiometabolic risk factors. Future investigations regarding PA, dementia, and cognitive decline may consider cardiometabolic risk factors such as hypertension, obesity, and glucose intolerance, and include repeated measures of PA over the life course.

Cognitive Impairment in Thalassemia and Associated Factors

Introduction: Patients with thalassemia increase the risk of developing cognitive impairment. Chronic anemia, oxidative stress from excess iron, and hypercoagulable state were related to this condition. The study regarding its prevalence and the associated factor in Southeast Asia is limited. Therefore, the study aimed to investigate the prevalence of cognitive impairment and associated factors. Methods: This was a cross-sectional study of thalassemic patients aged 18 years or more at the Hematology Clinic of Srinagarind Hospital, Khon Kaen University, Thailand, from January to May 2021. The Thai version of the Mini-Cog test was used to determine the presence of cognitive impairment. The clinical and laboratory parameters indicated as potential risk factors for dementia were evaluated in all patients. A stepwise logistic regression analysis was used to determine the associated risk factors for cognitive impairment. Results: Among 150 patients, cognitive impairment was found in 40 patients (26.7%). Age per 10-year increase (adjusted odds ratio [AOR] of 1.6), no iron chelation therapy (AOR of 9.8), current smoking (AOR of 5.0), hemoglobin (Hb) (AOR of 0.63), and ferritin (AOR of 1.0001) were independent factors associated with cognitive impairment. Conclusions: The prevalence of cognitive impairment was high among thalassemic patients. Increasing age, low Hb, iron overload, and current smoking were significant associated factors with cognitive impairment. Screening for dementia in these patients is recommended, particularly in patients with high-risk factors.

Health Care Utilization and Out-of-Pocket Payments among Elderly with Cognitive Frailty in Malaysia.

Background: Cognitive frailty (CF) as a potential risk factor for dementia, functional disability, poor quality of life, and mortality. The aim of this study was to explore the health care-related utilization and out-of-pocket (OOP) expenditures, sociodemographic characteristics, and comorbidities among elderly Malaysians with CF. Methods: A cross-sectional study targeting elderly Malaysian aged ≥65 years was conducted. The study included all participants of the fourth phase of the Malaysian representative Long-Term-Research-Grant-Scheme Towards-Useful-Aging (LRGS-TUA) community-based study. A structured and validated interview questionnaire was used. Results: In total, 1006 elderly were interviewed, with a 66.18% response rate. Only 730 respondents met the inclusion criteria. Of the eligible respondents, the CF prevalence was 4.5%. Around 60.6% of the participants with CF had utilized outpatient care at government clinics within the past 6 months. The estimated mean total OOP payments for CF during the past 6 months was 84 Malaysian Ringgit (RM) (SD 96.0). Conclusions: CF among elderly Malaysians is within the internationally recognized range of prevalence. The OOP payments for seeking health care among CF elderly are not different from that of other elderly categories. There is a high possibility of underutilization of the health care services of CF cases while they are still needy.