Sex-specific differences in the association between APOE genotype and metabolic syndrome among middle-aged and older rural Indians.

Background: Metabolic syndrome (MetS), characterized by elevated blood pressure, high blood glucose, excess abdominal fat, and abnormal cholesterol or triglyceride levels, significantly increases the risk of various non-communicable diseases. This study focuses on understanding the sex-specific association between Apolipoprotein E (APOE) polymorphism and MetS among middle-aged and older adults in rural southern India. Methods: This cross-sectional study utilized data from the Centre for Brain Research-Srinivaspura Aging, Neuro Senescence, and COGnition (CBR-SANSCOG) study. Participants (n = 3741) underwent comprehensive clinical assessments and blood investigations, including APOE genotyping. MetS was defined using the National Cholesterol Education Program - Adult Treatment Panel III (NCEP ATP III) and the Consensus criteria. Statistical analyses, including chi-square tests, ANCOVA, and logistic regression, were conducted to explore the association of APOE genotype with MetS and its components, stratified by sex. Results: Females carrying the APOE E4 allele had 1.31-fold increased odds of MetS (95 % CI: 1.02,1.69, p = 0.035) according to the NCEP ATP III criteria but not when the Consensus criteria were applied. The study also noted sex-specific differences in the association of APOE with various MetS components, including lipid levels and waist circumference. Discussion: Our findings reveal a sex-specific association between the APOE E4 allele and MetS, with only females having an increased risk. This study contributes to the understanding of the genetic underpinnings of MetS and highlights the importance of considering sex-specific differences in MetS research and its prevention strategies. This study underscores the complexity of MetS etiology and emphasizes the need for further research to elucidate the role of genetic, environmental, and lifestyle factors in its progression, particularly in sex-specific contexts.

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

INTRODUCTION: 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. METHODS: 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. RESULTS: 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. DISCUSSION: Rural Indians face significant healthcare disadvantages as compared to their urban counterparts, which prompts the urgent need for strategies for equitable healthcare.

Association between multilingualism and cognitive performance among older adults in rural southern India.

Objectives: Recent studies have shown that multilingualism may play an important role in enhancing cognitive health. The process of language acquisition constitutes a form of natural brain training, which in turn is hypothesized to increase neuroplasticity and hence, maintains the cognitive reserve. The study aimed to analyze the relationship between the number of languages known to an individual and its effect on cognitive functioning in both healthy and cognitively impaired study participants. Materials and Methods: This study utilized cross-sectional (baseline) data from Srinivasapura Aging, Neuro Senescence and COGnition study, which is an ongoing community-based, longitudinal aging cohort study conducted in a rural setting in southern India. A total of 3725 participants were considered for the study. The participants were separated into two groups, namely, monolinguals (participants knowing one language) and multilingual (participants knowing more than one language). The cognitive performance of the participants was assessed using the Clinical Dementia Rating (CDR) Scale. In addition, bivariate analyses and binary logistic regression analyses were carried out. Results: The result of CDR scores with respect to language category shows that, among the monolingual participants, 86.5% were healthy individuals and 13.5% were with mild cognitive impairment (MCI). Similarly, among the multilingual, 94.3% were healthy and 5.7% were with MCI. The odds ratio value derived from logistic regression (0.69 95% CI (0.5-0.9)) that an individual has a higher chance of developing cognitive impairment if he/she is a monolingual. Conclusion: This study highlights that knowing more than one language might have a profound positive impact on cognitive health, thereby reducing the likelihood of developing cognitive decline.

Association between ApoE ε4 genotype and attentional function in non-demented, middle-aged, and older adults from rural India.

Objectives: Several genetic factors have been associated with cognitive decline in aging. Apolipoprotein E (ApoE) ε4 has been widely studied in the risk for pathological cognitive decline, including dementia. However, the association between ApoE ε4 and cognitive functioning in the healthy aging Indian population has been understudied, and the results are ambiguous. Materials and Methods: This study aims to examine the role of the ApoE genotype with attentional function in aging adults (≥45 years) in a rural Indian population. Cross-sectional (baseline) data (n = 2100) was utilized from an ongoing longitudinal cohort study on aging (Srinivaspura Aging, Neurosenescence, and Cognition study). Participants hailed from villages of Srinivaspura in Karnataka, southern India. Participants were categorized based on ApoE-ε4 status into three categories: No ε4, heterozygous ε4, and homozygous ε4. Attentional function was assessed using the auditory and visual attention subtests from a computerized neurocognitive test battery. Linear regression was performed adjusting for age, gender, and education. Results: In model 1 (unadjusted), we did not find an association between ApoE and attention function. In the partially adjusted model 2 (adjusting for age), ApoE ε4 with age was significantly associated with the attention function. Further, with increasing age, there was a decline in attention among homozygous ε4 individuals. Model 3 (model 2 + gender) found that ApoE ε4, age, and gender explained a significant variance in attention function. In addition, with increasing age, males had poor attention in the homozygous as compared to heterozygous group. Model 4 (model 3+ education) explained a significant variance in attention and also revealed that with increasing age, attention declined in the illiterate and low literacy groups in both homozygous and heterozygous groups among both genders. Conclusion: Although ApoE ε4 alone was not associated, it interacted with age, gender, and education to affect attention function in this rural Indian population. Longitudinal cognitive monitoring will yield insights into understanding whether the ApoE ε4 genotype influences the rate of cognitive decline in this rural, aging population.

Relationship between Framingham Cardiovascular Risk Score and cognitive performance among ageing rural Indian participants: a cross-sectional analysis.

OBJECTIVE: The burden of cardiovascular risk factors is increasing in India, which, in turn, can adversely impact cognition. Our objective was to examine the effect of cardiovascular risk factors measured by Framingham Risk Score (FRS) on cognitive performance among a cohort of healthy, ageing individuals (n=3609) aged ≥45 years from rural India. DESIGN: A cross-sectional analysis. SETTING: A rural community setting in southern India. PARTICIPANTS: Healthy, ageing, dementia-free participants, aged 45 years and above, belonging to the villages of Srinivaspura (a rural community located around 100 km from Bangalore, India), were recruited. PRIMARY OUTCOME MEASURES: Using a locally adapted, validated, computerised cognitive test battery, we assessed cognitive performance across multiple cognitive domains: attention, memory, language, executive functioning and visuospatial ability. RESULTS: The median (IQR) age of the sample was 57 (50.65) and 50.5% were women. Multiple linear regression analysis showed that participants with higher FRS performed poorly in attention (visual attention (ß=-0.018, p=0.041)), executive functioning (categorical fluency (ß=-0.064, p<0.001)), visuospatial ability (form matching (ß=-0.064, p<0.001) and visuospatial span (ß=-0.020, p<0.001)), language (reading and sentence comprehension (ß=-0.010, p=0.013), word comprehension (ß=-0.021, p<0.001) and semantic association (ß=-0.025, p<0.001)), and memory (episodic memory IR (ß=-0.056, p<0.001), episodic memory DR (ß=-0.076, p<0.001) and name-face association (ß=-0.047, p<0.001)). CONCLUSION: Increased cardiovascular risk as evidenced by FRS was associated with poorer cognitive performance in all cognitive domains among dementia-free middle-aged and older rural Indians. It is imperative to design and implement appropriate interventions (pharmacological and lifestyle-based) for cardiovascular risk reduction and thereby, prevent or mitigate accelerated cognitive impairment in ageing individuals.

Impact of the COVID-19 pandemic on some modifiable risk factors of dementia in an aging, rural Indian population.

Introduction: The impact of the COVID-19 pandemic and associated lockdowns is likely to have caused adverse changes in lifestyle-related/cardiovascular risk factors and other such modifiable risk factors of dementia. We aimed to examine the pandemic's impact on some modifiable risk factors of dementia among rural Indians belonging to a large, prospective aging cohort-Srinivaspura Aging, NeuoSenescence, and COGnition (SANSCOG). Methods: This was a cross-sectional study among adults aged ≥ 45 years (n = 3,148; 1,492 males and 1,656 females) residing in the villages of Srinivaspura in Karnataka state, India. SANSCOG study data (clinical and biochemical assessments) of these participants were obtained from three distinct periods: (i) the "pre-COVID period"-before India's nationwide lockdown on 24 March 2020, (ii) the "COVID period"-during the first and second waves of the pandemic, wherein the social restrictions were prominent (25 March 2020 to 30 September 2021), and (iii) the "post-COVID period"-after easing of restrictions (from 1 October 2021 onward). Proportions of participants with diabetes, hypertension, obesity, dyslipidemia (diagnosed using standard criteria), and depression (diagnosed using the Geriatric Depression Scale) were compared between the above three periods. Results: The odds of having obesity, abnormal triglycerides, and depression among individuals in the COVID period were 1.42 times, 1.38 times, and 2.65 times more than the odds in the pre-COVID period, respectively. The odds of having hypertension, obesity, abnormal total cholesterol, abnormal triglycerides, abnormal LDL, and depression among individuals in the post-COVID period were 1.27 times, 1.32 times, 1.58 times, 1.95, 1.23, and 3.05 times more than the odds in the pre-COVID period, respectively. The odds of diabetes did not differ between any of the three periods. Discussion: We found significantly higher odds of some of the studied risk factors in the COVID and post-COVID periods compared to the pre-COVID period, suggesting that the pandemic adversely impacted the physical and psychological health of this marginalized, rural Indian population. We call for urgent public health measures, such as multimodal, lifestyle-based, and psychosocial interventions, to mitigate this negative impact and reduce the future risk of dementia.

Comparison of risk factors for dementia among rural and urban elderly adults-data from two cohort studies in India.

INTRODUCTION: Studies on risk factors for dementia in India, especially rural India, are sparse and therefore we aimed to assess risk factors in a rural cohort on aging and compare it with an urban cohort. METHODS: We are presenting baseline data on proportion of hypertension, diabetes, obesity, physical inactivity, and Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) scores in both cohorts. RESULTS: The rural cohort is younger and less educated than the urban cohort. The chi-square test showed that the proportion of participants with hypertension, diabetes, and obesity was lower in the rural cohort, whereas physical inactivity was higher in comparison with the urban cohort; however, the proportion of high-risk CAIDE scores was higher in the rural cohort. DISCUSSION: Despite the rural cohort having a smaller proportion of participants with hypertension, diabetes, and obesity, the overall CAIDE score was higher-the main reason for this is low educational level.

Prevalence of neuropsychiatric conditions and cognitive impairment in two parallel, aging study cohorts from rural and urban India.

INTRODUCTION: With the rising proportion of the elderly in India, the burden of neuropsychiatric conditions and cognitive impairment is escalating. METHODS: Baseline data of cognitively healthy subjects ≥45 years of age, from two longitudinal, aging cohorts in rural (n = 3262) and urban (n = 693) India, were used to calculate prevalence of depression, early-life stressful events, stroke, head injury, and cognitive impairment. RESULTS: Depression prevalence was significantly higher in rural than urban subjects, with female preponderance in both groups. Early life stressor (parental death) and head injury were significantly more common in rural than in urban India, whereas stroke was more in urban India. There was no significant difference in overall prevalence of cognitive impairment between the rural and urban cohorts; however, women had higher prevalence than men in rural, whereas this was reverse in urban subjects. Depression and stroke were significantly associated with cognitive impairment in the rural cohort. DISCUSSION: Longitudinal assessment of these neuropsychiatric conditions, with parallel cognitive monitoring, will help identify their causal relationship with dementia.

Approaches to engage an aging, rural cohort in southern India during the COVID-19 crisis and the psychological impact of COVID-19 in this cohort.

INTRODUCTION: The COVID-19 pandemic produced an unprecedented crisis across the world. Long-term cohort studies were stalled, including our longitudinal aging cohort study in rural India. METHODS: We describe approaches undertaken to engage with our cohort (n = 1830) through multiple rounds of calls and how we provided useful services to our subjects during the lockdown period. Consenting subjects also underwent telephonic assessments for depression and anxiety using validated, self-report questionnaires. RESULTS: Subjects reported benefitting from our telephonic engagement strategies, including the COVID-related safety awareness and counselling service. The proportion of subjects with depression increased from 7.42% pre-COVID to 28.97% post-COVID. DISCUSSION: We envisage that such engagement strategies would improve subject rapport and cohort retention, and thus, could be adopted by similar cohort studies across the world. This marginalized, rural Indian community had severe, adverse psychological impact in this pandemic. Urgent public health measures are needed to mitigate this impact and develop appropriate preventive strategies.

Depression and anxiety during the first and second waves of the COVID-19 pandemic in two large, prospective, aging cohorts in rural and urban India.

Introduction: The COVID-19 pandemic resulted in a wide variety of adverse consequences, including disruption of long-term, human research studies globally. Two long-term, prospective, aging cohort studies, namely, Srinivaspura Aging, Neurosenescence and COGnition (SANSCOG) study and Tata Longitudinal Study of Aging (TLSA), conducted in rural and urban India, respectively, had to be suspended during first and second waves of COVID-19. Methods: We conducted telephonic assessments to screen for depression and anxiety in the above two cohorts comprising of adults ≥45 years, during the first wave (2020) and second wave (2021) lockdown periods in India. Further, we included depression assessments data from two additional time periods-pre-COVID (2019) and the "inter-wave" period (between the first and second waves) to compare proportions of depression in these cohorts, during four distinct time periods-(i) pre-COVID, (ii) COVID first wave lockdown, (iii) inter-wave period, and (iv) COVID second wave lockdown (rural: 684, 733, 458, 611 and urban: 317, 297, 204, 305 respectively). Results: During COVID first wave, 28.8% and 5.5% had depression and anxiety, respectively in the rural cohort. Corresponding figures in the urban cohort were 6.5% and 1.7%. During second wave, 28.8% of rural subjects had depression and 3.9% had anxiety, whereas corresponding figures in urban subjects were 13.1% and 0.66%. During the above-mentioned four time periods, proportions of depression were: rural-8.3%, 28.8%, 16.6%, 28.8%; urban-12%, 6.1%, 8.8%, 13.1%. Conclusions: Multi-fold increase in depression among aging, rural Indians during first and second waves, with high depression among subjects ≥65 years and those with comorbidities during the first wave, is concerning. Urgent public health measures are needed to address this added mental health burden and thereby, prevent further potential adverse consequences.

Rural-urban and gender differences in metabolic syndrome in the aging population from southern India: Two parallel, prospective cohort studies.

Background: Despite the growing evidence of metabolic syndrome as a major risk factor for cardiovascular and cerebrovascular disease, there are limited studies from India on its prevalence, especially in the aging population. We aimed to estimate the prevalence of metabolic syndrome and associated comorbidities in two prospective, aging cohorts from rural and urban India. Methods: In these two parallel, prospective, aging (≥ 45 years) cohorts, the samples included 2171 people from rural India (Srinivaspura Aging, Neuro Senescence and COGnition, SANSCOG cohort; April 23, 2018 to Sept 25, 2021) and 332 people from urban India (Tata Longitudinal Study on Aging, TLSA cohort; July 8, 2015 to Oct 23, 2021). Using cross-sectional data from baseline clinical and biochemical assessments, we calculated metabolic syndrome prevalence using two well established criteria, namely consensus criteria and National Cholesterol Education Program - Adult Treatment Panel III (NCEP-ATP III) criteria; further, rural-urban, gender, and age-wise differences were compared. Findings: Proportions of metabolic syndrome were 46.2 and 54.8% as per consensus criteria in rural and urban participants, respectively; corresponding numbers using NCEP-ATP III criteria were 40.3 and 45.1%. Rural-dwelling older adults had a significantly lesser prevalence of all individual metabolic syndrome parameters except impaired triglycerides and high-density lipoprotein levels. Rural women had a significantly higher prevalence of metabolic syndrome than rural men, whereas there was no significant difference among urban participants. We did not observe any consistent age-wise trend when comparing both cohorts. There was high burden of comorbidities among both groups, mostly undiagnosed in rural participants. Interpretation: Roughly one in two older adults had metabolic syndrome, urban significantly more than rural, reaching an alarming 63.1% among urban participants aged 65-74 years. The very high prevalence of undiagnosed co-morbidities among rural adults is extremely concerning, calling for urgent public health measures in this marginalised and health-disparate population. Funding: SANSCOG study is funded through the Centre for Brain Research (CBR), Indian Institute of Science (IISc) by Pratiksha Trust, the philanthropic arm of Mr. Kris Gopalakrishnan. TLSA is funded by Tata Trusts.

Normative data for three physical frailty parameters in an aging, rural Indian population.

Introduction: Physical frailty is associated with multiple adverse health outcomes. Since physical characteristics markedly vary with different populations, population-specific norms for physical frailty parameters are necessary. Such norms are lacking for the Indian population, especially for older, rural Indians. We aimed to develop normative values for three quantitative, frailty parameters-handgrip strength, "Timed Up-and-Go" (TUG) test time, and physical activity in an aging, rural Indian population. Methods: The study sample is from an ongoing, prospective, cohort (Srinivaspura NeuoSenescence and COGnition, SANSCOG) comprised of rural, community-dwelling, cognitively healthy, aging Indians. Subjects are recruited through area sampling strategy, from villages of Srinivaspura, Kolar district, Karnataka state, India. Three physical frailty parameters of Fried's phenotype-handgrip strength (n = 1787), TUG time (n = 1863), and physical activity (n = 1640) were assessed using digital hand dynamometry, TUG test, and General Physical Activity Questionnaire (GPAQ), respectively. Results: The 10th, 25th, 50th, 75th, 90th percentiles for the three frailty parameters were: right-hand grip strength (kg): males-13.9, 18.6, 23.8, 28.7, 33.7 and females-7.8, 10.6, 14.2, 17.9, 21.3; left-hand grip strength (kg): males-13.3, 18.3, 23.6, 28.9, 32.9 and females-7.9, 10.5, 14.3, 17.8, 21.2; TUG time (s): males-9.1, 10.1, 11.4, 13.4, 15.5 and females-9.5, 10.7, 12.4, 14.5, 16.6; physical activity (MET-minutes/week): males-1680; 4320; 8880; 15,840; 23,352 and females-1680; 4320; 9240; 15,120; 20,160. Discussion: Our findings show that from 45 years onwards, overall grip strength decreases and TUG time increases, with women performing significantly poorer than men across all age groups, except >75 years, where no differences were seen. Physical activity did not show any consistent trend according to age or gender. Reference values for this aging, rural Indian population were substantially lower for grip strength and higher for TUG time than aging populations in several Western and other Asian countries.

Changing demography and the challenge of dementia in India.

In India, increasing lifespan and decreasing fertility rates have resulted in a growing number of older persons. By 2050, people over 60 years of age are predicted to constitute 19.1% of the total population. This ageing of the population is expected to be accompanied by a dramatic increase in the prevalence of dementia. The aetiopathogenesis of dementia has been the subject of a number of prospective longitudinal studies in North America and Europe; however, the findings from these studies cannot simply be translated to the Indian population. The population of India is extremely diverse in terms of socio-economic, cultural, linguistic, geographical, lifestyle-related and genetic factors. Indeed, preliminary data from recently initiated longitudinal studies in India indicate that the prevalence of vascular and metabolic risk factors, as well as white matter hyperintensities, differs between urban and rural cohorts. More information on the complex role of vascular risk factors, gender and genetic influences on dementia prevalence and progression in Indian populations is urgently needed. Low-cost, culturally appropriate and scalable interventions need to be developed expeditiously and implemented through public health measures to reduce the growing burden of dementia. Here, we review the literature concerning dementia epidemiology and risk factors in the Indian population and discuss the future work that needs to be performed to put in place public health interventions to mitigate the burden of dementia.

Burden of Vitamin D, Vitamin B12 and Folic Acid Deficiencies in an Aging, Rural Indian Community.

Introduction: The important role of micronutrient deficiencies in aging-related disorders including dementia is becoming increasingly evident. However, information on their burden in India is scarce, especially, among aging and rural communities. Methods: Prevalence of vitamin D, B12 and folic acid deficiency was measured in an ongoing, aging cohort, from rural India-Srinivaspura Aging Neurosenescence and COGnition (SANSCOG) study cohort. Serum level estimation of vitamin D, B12 and folic acid, using chemiluminescence immunoassay, was performed on 1648 subjects (872 males, 776 females). Results: Mean vitamin D, B12 and folic acid levels were 23.4 ± 10.6 ng/ml, 277.4 ± 194.4 pg/ml and 6 ± 3.5 ng/ml), respectively. Prevalence of low vitamin D (<30 ng/ml), vitamin D deficiency (<20 ng/ml), B12 deficiency (<200 pg/ml) and folic acid deficiency (<3 ng/ml) were 75.7, 39.1, 42.3, and 11.1%, respectively. Significantly more women had vitamin D deficiency, whereas more men had folic acid deficiency. Women belonging to the oldest age group (≥75 years) had the maximum burden of low vitamin D (94.3%) and folic acid deficiency (21.8%). Discussion: Older, rural-dwelling Indians have high burden of vitamin D and B12 deficiencies, which is concerning given the potentially negative consequences on cognition, immunity and frailty in the aging population. Urgent public health strategies are needed to address this issue and prevent or mitigate adverse consequences.