Risk Factor For Dementia Research Articles

Low Intake of Total Antioxidant Nutrients as a Risk Factor for Incident Dementia in Older Adults: The Shanghai Aging Study

Introduction: Previous longitudinal studies reported the impact of antioxidant nutrients (ANs) on cognitive impairment in the older population, but the conclusions were inconsistent. This study aimed to verify the hypothesis that dietary intake of total AN was associated with incident dementia among older individuals. Methods: Community residents without dementia aged ≥60 years were prospectively followed up for an average of 5.2 years in the Shanghai Aging Study. At baseline, daily intakes of total dietary AN (the sum of carotene, vitamin C, vitamin E, lutein, and flavonoids) and energy were calculated based on an interviewer-administered food frequency questionnaire measuring the dietary intake over the past 1 year for each participant. A battery of neuropsychological tests was used to evaluate cognitive function, and a consensus diagnosis of dementia was made according to the DSM-IV criteria at baseline and follow-up. Results: Among 1,550 dementia-free participants, 135 (8.7%) incident dementia cases were identified during the average of 5.2 years of follow-up. Participants with low AN intake (<112 mg/day) had a significantly higher risk of incident dementia than those with high AN intake (≥112 mg/day) (hazard ratio 1.87, 95% confidence interval 1.26–2.77) after adjusting for age, gender, education, obesity, APOE-ε4, hypertension, diabetes, depression, baseline Mini-Mental State Examination score, and total energy intake. The significant association of total AN intake with incident dementia was only found in individuals ≥70 years. Conclusion: Low total AN intake may be a risk factor for incident dementia among older adults. Maintaining sufficient AN intake may be beneficial against age-related cognitive decline.

Association between surgical admissions, cognition, and neurodegeneration in older people: a population-based study from the UK Biobank

Previous studies have shown that major surgical and medical hospital admissions are associated with cognitive decline in older people (aged 40-69years at recruitment), which is concerning for patients and caregivers. We aimed to validate these findings in a large cohort and investigate associations with neurodegeneration using MRI. For this population-based study, we analysed data from the UK Biobank collected from March 13, 2006, to July 16, 2023, linked to the National Health Service Hospital Episode Statistics database, excluding participants with dementia diagnoses. We constructed fully adjusted models that included age, time, sex, Lancet Commission dementia risk factors, stroke, and hospital admissions with a participant random effect. Primary outcomes were hippocampal volume and white matter hyperintensities, both of which are established markers of neurodegeneration, and exploratory analyses investigated the cortical thickness of Desikan-Killiany-Tourville atlas regions. The main cognitive outcomes were reaction time, fluid intelligence, and prospective and numeric memory. Surgeries were calculated cumulatively starting from 8years before the baseline evaluation. Of 502 412participants in the UK Biobank study, 492 802participants were eligible for inclusion in this study, of whom 46 706underwent MRI. Small adverse associations with cognition were found per surgery: reaction time increased by 0·273ms, fluid intelligence score decreased by 0·057correct responses, prospective memory (scored as correct at first attempt) decreased (odds ratio 0·96 [95% CI 0·95to 0·97]), and numeric memory maximum correct matches decreased by 0·025in fully adjusted models. Surgeries were associated with smaller hippocampal volume (β=-5·76mm³ [-7·89to-3·64]) and greater white matter hyperintensities volume (β=100·02 mm³ [66·17to 133·87]) in fully adjusted models. Surgeries were also associated with neurodegeneration of the insula and superior temporal cortex. This population-based study corroborates that surgeries are generally safe but cumulatively are associated with cognitive decline and neurodegeneration. Perioperative brain health should be prioritised for older and vulnerable patients, particularly those who have multiple surgical procedures. The Australian and New Zealand College of Anaesthetists (ANZCA) Foundation and the University of Sydney.

Impact of multiple infections on risk of incident dementia according to subjective cognitive decline status: a nationwide population-based cohort study.

The interrelation between infections, subjective cognitive decline (SCD), and dementia development is recognized, but not fully understood. This study explored the combined effect of specific infections and SCD on the risk of dementia. To assess the influence of Helicobacter pylori, herpes simplex virus, varicella-zoster virus, and human papillomavirus on dementia risk in individuals with varying cognitive statuses, especially focusing on those with and without SCD. A cohort of 1,100,540 participants aged 66 years from the Korean National Health Insurance Service was divided into cognitively preserved (CP, n = 825,405) and SCD (n = 275,135) groups. This study analyzed the effects of single, dual, and triple infections on the risk of overall dementia, Alzheimer's disease (AD), and vascular dementia (VaD) using incidence rates and hazard ratios. The SCD group consistently showed a doubled risk of dementia, particularly AD, regardless of the number of infections. In the initial data, both the presence and number of infections, especially in the CP group, were associated with an increased dementia incidence and risk; however, this correlation disappeared after adjusting for covariates, hinting at a possible protective effect. Our findings emphasize that, while SCD is a steadfast risk factor for dementia, the role of infections is layered, subject to various influences, and requires more comprehensive exploration to fully understand their impact on dementia development.

One year analysis of Prospective Memory Clinics Registry in Qatar: A Critical Tool for Dementia Research and Policy Planning.

The Global Dementia Observatory (GDO) is a monitoring and accountability tool for the Global Action Plan on Public Response to Dementia 2017-25. Evidence from dementia registries may be utilized to better address WHO efforts in member countries, as well as to improve clinical practice and public health policy. The goal of this study was to analyze one-year data from a prospective memory clinic registry. This study was a baseline analysis of prospective memory clinics registry data of Qatar from January 1, 2023, through December 31, 2023. This study investigated the demographic, clinical, and lifestyle characteristics of 464 participants who were enrolled in memory clinics. Mild neurocognitive disorders were the most prevalent diagnoses in both sexes, affecting 61.5% of male patients and 63.7% of female patients. Dementia was slightly more common in men (19.8% vs. 18.9%), although delirium was more common in women (1.9% vs. 0%). In terms of risk factors, the analysis revealed that females were more likely to be obese (36.8% vs. 16.7% in males), while males had higher rates of diabetes (61.1% vs. 51.9% in females), hypertension (69.4% vs. 62.7% in females), and smoking (17.1% vs. 3.8% in females). The findings of this study highlight the differences in dementia risk factors between genders and races, highlighting the need for customized interventions. Furthermore, the registry is a great resource for policymakers and healthcare professionals, providing evidence-based suggestions to improve dementia care, increase the well-being of patients and caregivers, and maximize resource allocation.

Abstract P134: Effects of Antihypertensive Medications on All-cause Dementia: Evidence from Target Trial Emulation of 3 Million US Veterans

Introduction: Hypertension is a modifiable risk factor for all-cause dementia. Mechanistic and observational evidence suggest angiotensin receptor blockers (ARBs) and angiotensin converting enzyme inhibitors (ACEIs) may differentially affect dementia risk. Objective and Methods: We used longitudinal electronic health records of over 3 million US Veterans to conduct a target trial emulation with a new-user, active comparator design. We compared the intention-to-treat effect of initiating ARBs vs ACEIs (1/1/2000-12/31/2022) on dementia risk. We controlled for &gt;60 baseline covariates using inverse probability (IP) of treatment and overlap weighting. Dementia was ascertained using diagnosis codes and medications. We nonparametrically estimated the cause-specific cumulative incidence for each treatment group under the competing risk of death then computed treatment effects as weighted risk ratios with bootstrapped 95% confidence intervals. We also evaluated all-cause death and a composite outcome of dementia or death (dementia/Death) using Cox regression. Results: Among the 3,190,356 included Veterans (mean age 63, 5% female, 64% White, and 15% Black), 13% initiated ARBs and 87% initiated ACEIs. Overall, 8% developed dementia and 35% died over a median follow-up of 8 years. The risk of dementia was lower among ARB vs ACEI initiators (10-year risk ratio: 0.95 (0.94, 0.96)). The risk of all-cause death and dementia/Death were also lower among ARB vs ACEI initiators with overlap weighting. Conclusions: Among US Veterans with hypertension, ARB vs ACEI initiation was associated with a moderately lower risk of dementia. Future work assessing sustained treatment with ARB vs ACEI is needed to inform their use to reduce dementia risk.

Abstract 22: Evaluation of the effects of CD8 knock-out on cognitive decline in the TAC-induced hypertension mouse model

Hypertension is one of the main risk factors for cognitive impairment and dementia. We and others demonstrated the role of immunoinflammatory challenges in the establishment of cerebral injury following hypertension, highlighting a major role of inflammatory cytokines as interferon-gamma (IFN-γ) and finding increased parenchymal infiltration of CD8+ T cells. To establish the mechanistic role of these cells in cognitive impairment we subjected mice lacking CD8 cells (CD8 KO) and matched controls to aortic coarctation (TAC) and performed advanced neuroimaging analyses with a dedicated 7T small animal MRI, evaluating perfusion, brain volumes, and white matter microstructural integrity. Cognitive performance was evaluated at 4 weeks using the Morris Water Maze (MWM) test. Brain perfusion analyses shown protection from cerebral hypoperfusion in TAC CD8 KO mice compared to TAC WT mice (TAC WT vs TAC KO: 108 vs 148 ml/100g/min, p=0.0298) (Figure A). CD8 KO show preserved microstructural structure at DTI MRI, a typical trait of cerebral injury in clinical and experimental hypertension (Fimbria Fractional Anisotropy, TAC WT vs TAC KO: 0.45 vs 0.54, p=0.0210) , and show no a preserved cognition at MWM (Figure B), with a preserved learning curve at acquisition trial and a preserved memory retention capability evidenced at the probe trial (TAC WT vs TAC KO: 16,4 vs 32.2 seconds spent in platform quadrant, p=0.0014). The rescue from cerebral injury evidenced at MRI and the absence of cognitive impairment in CD8 KO mice demonstrate the pivotal role of CD8+ lymphocytes in the pathogenesis of hypertension-induced cognitive impairment.

Abstract P329: Mycophenolate Mofetil Enhances Short-Term Blood Pressure Variability During Recovery in Salt-Sensitive Hypertensive African Americans

Elevated blood pressure variability (BPV) is an independent risk factor for cardiovascular disease (CVD), kidney disease, dementia, and stroke. High BPV is thought to be caused by arterial stiffness, vascular remodeling, inflammatory cascades, and neurohormonal mechanisms. This study aims to investigate the potential impact of mycophenolate mofetil (MMF) on short-term BPV in the context of salt-sensitive hypertension among African Americans (AA). MMF’s anti-inflammatory properties hold promise as a potential intervention for hypertension management by modulating short-term BPV. AA participants,18-50 years, normotensive, not pregnant, and not on prescription medications were recruited. In this crossover study, 51 participants received either MMF or a placebo daily. Physiological parameters were monitored every 15 minutes during a 3-hour psychosocial stressor assessment with rest, stress, and recovery periods. BPV was assessed using coefficient of variation (CV), standard deviation (SD), and average real variability (ARV). The treatment group showed a significant decrease in SBP CV (p &lt; 0.05) during stress. During recovery, SBP SD (p, 0.05) and SBP ARV (p &lt; 0.05) significantly increased in individuals receiving MMF treatment. Age-stratified analysis maintained significant effects of MMF on BPV during stress. Gender did not significantly alter the observed effects of MMF on BPV. Our study highlights the effectiveness of MMF in reducing BPV during acute stress, potentially lowering adverse cardiovascular events. MMF-treated groups showed increased BPV during recovery, indicating a quicker BP recovery to baseline. While a decrease in BPV during the stress period was observed, it was supported only by CV. The significant increase in BPV in the treatment group during recovery indicates MMF's ability to expedite the inflammatory stress response. The observed decrease in BPV during stress suggests a swifter return to baseline BP, potentially offering benefits for non-stress baseline physiology. Further research is warranted to clarify the mechanisms and clinical significance of these findings, impacting hypertension assessment and management. MMF treatment induces distinct changes in BPV during recovery, suggesting that MMF may positively influence BP regulation through a variety of inflammatory pathways. The alterations in SBP BPV underscore MMF's therapeutic potential for managing BPV and reducing cardiovascular risk in salt-sensitive, hypertensive AAs.

A Systematic Review of Antidepressants and Psychotherapy Commonly Used in the Treatment of Late Life Depression for Their Effects on Cognition

Cognitive dysfunction is common in late life depression (LLD) and is a major risk factor for dementia. Recent studies show limited improvement in cognition with commonly employed treatments for LLD, contradicting the notion that cognition "returns to normal" with treatment. However, findings differ with the treatments used. The aim of this study is to perform a systematic review of studies of antidepressants and psychotherapies commonly employed in LLD to determine their effects on cognition, particularly processing speed, memory, and executive function. We searched for trials of acute phase treatment, in nondemented individuals 60 years and older with unipolar nonpsychotic Major Depressive Disorder, that assessed cognitive performance with neuropsychological tests before and after treatment. We compared the magnitude of change in cognition by examining within group effect sizes. Six antidepressant trials and two psychotherapy trials (both using Problem Solving Therapy)(PST) provided relatively comparable data that allowed for quantitative comparison. Nine other antidepressant trials provided descriptive findings. Sertraline and vortioxetine had significant positive effects on processing speed and memory. Duloxetine had significant effects on memory. The most selective SRIs-citalopram and escitalopram-had minimal effects on cognition and citalopram had adverse effects in depression nonresponders. PST had modest effects on processing speed and no effect on memory. Effects of practice and improvement in depression on cognition are examined. In all but one study, cognition was a secondary outcome and various quality indicators (e.g. blinding cognitive assessment to treatment) were often not reported. As a consequence, these findings must be considered preliminary.

Guardians of memory: The urgency of early dementia screening in an aging society.

The global aging population has led to a significant rise in the prevalence of age-related non-communicable diseases such as dementia and other cognitive disorders. In 2019, there were 57.4 million people with dementia worldwide, and this number is projected to triple by 2050. Intervening in and managing 12 potentially modifiable dementia risk factors can prevent or delay the onset and progression of about 40% of dementia cases. Neuroimaging, biomarkers, and advanced neuropsychological testing offer promising pathways for the early detection of dementia. Emphasis should be placed on educating the public about the importance of brain health and the early signs of cognitive impairment, as well as promoting dementia prevention measures. Adopting a healthy lifestyle - including a balanced diet, regular physical exercise, active social engagement, cognitive activities, and avoiding smoking and excessive alcohol consumption - can help reduce the risk of cognitive decline and prevent cognitive disorders. Government policies on dementia prevention and health care, along with early and regular dementia screening programs, can enhance the early identification and management of individuals at risk. In addition, integrating cognitive health assessments into routine medical check-ups is essential for the early screening and management of dementia.

Blood-based multivariate methylation risk score for cognitive impairment and dementia.

The established link between DNA methylation and pathophysiology of dementia, along with its potential role as a molecular mediator of lifestyle and environmental influences, positions blood-derived DNA methylation as a promising tool for early dementia risk detection. In conjunction with an extensive array of machine learning techniques, we employed whole blood genome-wide DNA methylation data as a surrogate for 14 modifiable and non-modifiable factors in the assessment of dementia risk in independent dementia cohorts. We established a multivariate methylation risk score (MMRS) for identifying mild cognitive impairment cross-sectionally, independent of age and sex (P=2.0×10-3). This score significantly predicted the prospective development of cognitive impairments in independent studies of Alzheimer's disease (hazard ratio for Rey's Auditory Verbal Learning Test (RAVLT)-Learning=2.47) and Parkinson's disease (hazard ratio for MCI/dementia=2.59). Our work shows the potential of employing blood-derived DNA methylation data in the assessment of dementia risk. We used whole blood DNA methylation as a surrogate for 14 dementia risk factors. Created a multivariate methylation risk score for predicting cognitive impairment. Emphasized the role of machine learning and omics data in predicting dementia. The score predicts cognitive impairment development at the population level.

Brain Care Score and Neuroimaging Markers of Brain Health in Asymptomatic Middle-Age Persons.

To investigate associations between health-related behaviors as measured using the Brain Care Score (BCS) and neuroimaging markers of white matter injury. This prospective cohort study in the UK Biobank assessed the BCS, a novel tool designed to empower patients to address 12 dementia and stroke risk factors. The BCS ranges from 0 to 21, with higher scores suggesting better brain care. Outcomes included white matter hyperintensities (WMH) volume, fractional anisotropy (FA), and mean diffusivity (MD) obtained during 2 imaging assessments, as well as their progression between assessments, using multivariable linear regression adjusted for age and sex. We included 34,509 participants (average age 55 years, 53% female) with no stroke or dementia history. At first and repeat imaging assessments, every 5-point increase in baseline BCS was linked to significantly lower WMH volumes (25% 95% CI [23%-27%] first, 33% [27%-39%] repeat) and higher FA (18% [16%-20%] first, 22% [15%-28%] repeat), with a decrease in MD (9% [7%-11%] first, 10% [4%-16%] repeat). In addition, a higher baseline BCS was associated with a 10% [3%-17%] reduction in WMH progression and FA decline over time. This study extends the impact of the BCS to neuroimaging markers of clinically silent cerebrovascular disease. Our results suggest that improving one's BCS could be a valuable intervention to prevent early brain health decline.

Could the Early Detection of Atrial Fibrillation Reduce the Risk of Developing Dementia?

Atrial fibrillation (AF) and dementia are major global public health issues and share common risk factors, especially after the age of 65 and regardless of the presence of stroke. Despite accounting for potential confounders, AF appears to be an independent risk factor for cognitive decline and dementia. The mechanisms are likely to be multifactorial and may include AF-related ischemic stroke, cerebral hypoperfusion, microbleeds, systemic inflammation, genetic factors, and small vessel disease, leading to brain atrophy and white matter damage. The early aggressive management of AF and comorbidities may reduce the risk of dementia. Indeed, the early detection of AF-related cognitive impairment should allow for the early implementation of measures to prevent the development of dementia, mainly through integrative approaches involving the correction of risk factors and maintenance of rhythm control. Well-designed prospective studies are needed to determine whether early detection and AF treatment can prevent dementia and identify whether optimal integrative measures are effective in preventing cognitive impairment and dementia.

Radiographic Knee Osteoarthritis Is a Risk Factor for the Development of Dementia: Locomotive Syndrome and Health Outcomes in the Aizu Cohort Study.

Osteoarthritis is linked to dementia, but no longitudinal studies have established this connection. This prospective cohort study from the Locomotive Syndrome and Health Outcome in Aizu Cohort Study (LOHAS) aimed to determine if knee osteoarthritis (KOA) independently predicts dementia in adults aged 65 and above. Participants were classified by the Kellgren-Laurence scale into no/minimal KOA (grades 0 and I) and definitive KOA (grade II or higher). We analyzed dementia incidence from 2009 to 2015 using long-term care insurance data, adjusting for age, sex, vascular risks, depressive symptoms, and activity levels. Out of 1089 participants (58.9% female, average age 72.5), 72.0% had definitive KOA. Dementia occurrence was significantly higher in the definitive group (8.4%) compared to the no/minimal group (3.0%) (p < 0.001). A log-rank test and Cox regression analysis confirmed these findings, showing an adjusted hazard ratio of 2.29 (confidence interval: 1.12-4.68) for dementia in those with definitive KOA. These results suggest that KOA is a significant risk factor for dementia, highlighting the importance of addressing contributing factors in KOA patients to potentially slow the progression of dementia.

Relationships of hematocrit concentration with dementia from a multiethnic population-based study.

Red blood cell (RBC) concentration impacts cerebrovascular disease, yet it is unclear whether RBC concentrations relate to dementia risk, particularly in racially/ethnically diverse cohorts. We investigated whether RBC concentrations associate with incident dementia risk in a diverse population of stroke-free individuals and explored whether cerebral small vessel disease (CSVD) mediates this relationship. A longitudinal observational analysis was performed using a population-based cohort of stroke-free, older adult participants (>50 years) from the Northern Manhattan Study (NOMAS) enrolled between 2003-2008. Participants received baseline hematocrit testing, MRI neuroimaging, and cognitive assessments at baseline and long-term follow-up. Associations of baseline hematocrit as a categorical variable (low, normal [reference], and high based on laboratory reference levels) with incident dementia were assessed using Cox models adjusting for relevant covariates. Separate analyses investigated whether MRI CSVD mediated these relationships. We studied 1207 NOMAS participants (mean age 71±9 years, 60% female, 66% Hispanic). Mean hematocrit was 41.2% (±3.8) with 16% of participants developing incident dementia. Lower hematocrit associated with increased dementia risk (adjusted hazard ratio 1.81 [1.01-3.23]) after adjusting for age, sex, race/ethnicity, education, APOE status, and comorbidities. High hematocrit was not associated with dementia risk. No interactions by sex or race/ethnicity were seen and baseline CSVD did not mediate relationships between hematocrit and dementia. Low hematocrit associated with dementia risk in our diverse population cohort. Further work is needed to assess mechanisms behind anemia's relationship with dementia to assess whether this can serve as a trackable, preventable/treatable risk factor for dementia.

Sex Matters: Association with Superager Classification and Risk Factors.

Superagers are 80 to 89-year-olds with average or better cognition and memory equivalent to individuals 20 to 30years younger. As sex and modifiable lifestyle/health factors influence cognitive aging and dementia risk, we examined their impact on superager status. Data from participants (n = 469; 67% female) aged 80-89years old were analyzed from an online database that included demographic and dementia risk factors, and performance on tasks assessing working memory, cognitive inhibition, associative memory, and set shifting. Cross-sectional comparisons were made between superagers and those with typical-for-age cognitive abilities (typical-agers) to examine relationships between sex, superager status, and dementia risk factors. Females performed better than age-matched males on the associative memory task in the 50-69years old group used for normative comparisons, and in the 80-89years old group (ps < .001). More females than males were classified as superagers using non-sex-stratified normative comparisons (p = .009), and in sex-stratified normative comparisons (p = .022). Total weighted dementia risk reduced odds of superager status (OR = 0.199, 95% CI [0.046, 0.829]). Other lifestyle dementia risk factors were unrelated to superager status or could not be tested due to low endorsement. The findings support observations that superaging is more common in females, even when controlling for sex differences in memory performance. Future studies of superagers should account for sex differences. Results support being ambitious about dementia prevention, as having fewer modifiable dementia risk factors may be positively associated with superager status.

"How will I ever know I didn't bring it on myself?": Navigating personal responsibility in public health messaging on dementia risk.

Public health messaging increasingly emphasizes the importance of "lifestyle interventions" to reduce dementia risk. Our study aimed to understand how people interpret and respond to information about dementia risk. In a second sub-aim, we examined how these interpretations may contribute to dementia-related lifestyle stigma. We engaged in a secondary analysis of 50 semi-structured interviews using a framework approach to understand, from the perspective of community-dwelling middle-aged and older adults, how they may interpret, make sense of, and respond to information about dementia risk and risk reduction. During the interpretive and narrative phase, the authors began to elucidate participant responses analytically and identified that these responses could be interpreted within the health locus of control literature. Of the 23 participants who discussed dementia risk, 13 felt some sense of personal responsibility and control over their dementia risk. Of those 13, four participants believed they had personal responsibility and control and actively engaged in lifestyle interventions. The remaining nine participants also engaged in lifestyle interventions, aiming to find comfort in knowing they had done what they could to reduce their risk and working to alleviate self-attribution of blame if diagnosed with dementia. The tendency to internalize responsibility may inadvertently contribute to the stigmatization of dementia as a 'lifestyle disease' creating dementia-related lifestyle stigma. Recognizing the multifaceted nature of dementia risk, including environmental and external factors beyond individual control, is essential to combatting the 'lifestyle stigma' increasingly associated with the condition.

Impact of Helicobacter pylori eradication on age-specific risk of incident dementia in patients with peptic ulcer disease: a nationwide population-based cohort study.

The impact of peptic ulcer disease (PUD) and Helicobacter pylori (H. pylori) eradication therapy on dementia risk in high H. pylori prevalence populations remains uncertain. This study investigates the relationship between PUD, H. pylori eradication, and dementia risk, including Alzheimer's disease (AD), in an elderly South Korean cohort, considering age and eradication timing. Data from the Korean National Health Insurance Service (2002-2015) for individuals aged 55-79 were analyzed. Participants were divided based on PUD and H. pylori therapy status. Propensity score matching was used to evaluate dementia incidence and hazard ratios over 5 and 10 years, alongside the timing of eradication therapy. PUD is linked to higher dementia risk at 5 and 10 years, more for overall dementia than AD, with eradication status not significantly altering the risk. Age-specific analysis showed increased AD risk in the 60s and 70s age groups. Late eradication therapy is correlated with a higher dementia risk. PUD is a risk factor for dementia in elderly South Koreans, particularly with delayed H. pylori therapy. The findings emphasize timely H. pylori management and its potential role in neurodegenerative disease prevention.

Region-based analysis with functional annotation identifies genes associated with cognitive function in South Asians from India.

The prevalence of dementia among South Asians across India is approximately 7.4% in those 60 years and older, yet little is known about genetic risk factors for dementia in this population. Most known risk loci for Alzheimer's disease (AD) have been identified from studies conducted in European Ancestry (EA) but are unknown in South Asians. Using whole-genome sequence data from 2680 participants from the Diagnostic Assessment of Dementia for the Longitudinal Aging Study of India (LASI-DAD), we performed a gene-based analysis of 84 genes previously associated with AD in EA. We investigated associations with the Hindi Mental State Examination (HMSE) score and factor scores for general cognitive function and five cognitive domains. For each gene, we examined missense/loss-of-function (LoF) variants and brain-specific promoter/enhancer variants, separately, both with and without incorporating additional annotation weights (e.g., deleteriousness, conservation scores) using the variant-Set Test for Association using Annotation infoRmation (STAAR). In the missense/LoF analysis without annotation weights and controlling for age, sex, state/territory, and genetic ancestry, three genes had an association with at least one measure of cognitive function (FDR q<0.1). APOE was associated with four measures of cognitive function, PICALM was associated with HMSE score, and TSPOAP1 was associated with executive function. The most strongly associated variants in each gene were rs429358 (APOE ε4), rs779406084 (PICALM), and rs9913145 (TSPOAP1). rs779406084 is a rare missense mutation that is more prevalent in LASI-DAD than in EA (minor allele frequency=0.075% vs. 0.0015%); the other two are common variants. No genes in the brain-specific promoter/enhancer analysis met criteria for significance. Results with and without annotation weights were similar. Missense/LoF variants in some genes previously associated with AD in EA are associated with measures of cognitive function in South Asians from India. Analyzing genome sequence data allows identification of potential novel causal variants enriched in South Asians.

Hearing Loss and Cognitive Impairment Among Community-Dwelling Older Adults - Liaoning, Henan, and Guangdong Provinces, China, 2019-2020.

Many studies have shown that hearing loss (HL) is a risk factor for cognitive decline and dementia, but there are still limited studies on this association among Chinese older adults. Based on the results of pure-tone audiometry tests, HL is associated with cognitive impairment in community-dwelling older adults. The odds ratios (ORs) were 1.23 (1.08-1.40) for mild HL, 1.55 (1.32-1.82) for moderate HL, and 1.87 (1.47-2.39) for severe or profound HL. Enhanced public awareness of hearing protection is important for preventing cognitive impairment. It is advocated to promote the screening of HL and cognitive function assessment in elderly health examinations or management in primary care services.

The Influence of Vision Impairment on the Measurement of Cognition in Older Adults in India: Findings From LASI-DAD.

Prior investigations have not considered whether poor vision biases cognitive testing. However, such research is vital given increasing evidence that vision impairment (VI) may be an important modifiable risk factor for dementia, particularly in low- and middle-income settings where the prevalence of VI is high. This study employed data from 3784 participants in Wave 1 of the Longitudinal Aging Study in India-Diagnostic Assessment of Dementia (LASI-DAD) who underwent both visual acuity and cognitive function testing. We used multiple indicators and multiple causes models to assess differential item functioning (DIF; eg, bias) in cognitive testing by objectively measured distance and near VI. Multivariable linear regression was used to model the association between VI and cognitive factor scores before and after DIF adjustment. Analyses were performed for general cognition and separate cognitive domains, corresponding to memory, language/fluency, executive functioning, and visuospatial performance. Models were adjusted for demographic, health, and socioeconomic covariates. Participants in our sample were 60 and older. Most participants with VI were 60-69 years old (59.6%) and 50.8% were female. Individuals experiencing both distance and near VI tended to be older, have lower educational attainment, be married, reside in rural settings, and belong to lower consumption and BMI categories. Both distance and near VI were associated with poorer cognition before and after DIF-adjustment. Differences between DIF-unadjusted and -adjusted scores were small compared to the standard error of measurement, indicating no evidence of meaningful measurement differences by VI. In well-conducted large-scale surveys, bias in cognitive testing due to VI is likely minimal. Findings strengthen previous evidence on the association between VI and dementia by showing that such associations are unlikely to be attributable to vision-related measurement error in the assessment of cognitive functioning.