Background:Amnestic mild cognitive impairment (aMCI) represents a transitional stage between normal aging and Alzheimer disease (AD), where early intervention is critical for preserving cognition and delaying or preventing progression to dementia. Due to the limited availability of curative pharmacological treatments, there is growing interest in traditional and indigenous medicinal interventions, such as Bacopa monnieri (Linn.) or Brahmi, a widely used Ayurvedic nootropic herb. Bacopa consumption is known to enhance cognitive performance in healthy individuals and is associated with alterations in pathways related to branched-chain and aromatic amino acid biosynthesis. These pathways have been implicated in MCI due to AD pathophysiology. Hence, the efficacy of Bacopa in aMCI and the mediating metabolic changes need to be systematically evaluated through clinical trials. Objective:The aim of this study is to assess the effects of B. monnieri on cognitive function and plasma metabolites in individuals with aMCI (early or prodromal AD). Methods:This study will employ a double-blind, randomized, placebo-controlled trial design, with 76 participants (38 per group) of aMCI diagnosed using the clinical National Institute on Aging-Alzheimer's Association 2011 criteria in a tertiary care setting in India. Participants will receive either B. monnieri (Linn.) (300 mg standardized plant extract) or a matched placebo daily for 12 weeks. Comprehensive cognitive assessments (0, 12, and 24 wk) and untargeted plasma metabolomic profiling (0 and 12 wk) will be conducted to evaluate both cognitive changes and alterations in plasma metabolites. MetaboAnalyst 6.0 (with integrated features like Kyoto Encyclopedia of Genes and Genomes and the Human Metabolome Database) will be used for a comprehensive statistical and functional analysis pertaining to the metabolomics. The primary outcome will be a change in the composite z score of memory between the 2 groups at 12 weeks. The secondary outcomes will include alterations in metabolites and pathways, and adverse events at 12 weeks, and cognitive performance at 12 and 24 weeks. Results:The study was funded in October 2023, and the first participant was enrolled in April 2024. As of November 2025, a total of 60 participants have been recruited, with a mean (SD) age of 62.2 (8.1) years. The cohort predominantly comprises men (53/60, 88.3%), individuals with at least a high school education (47/60, 78.3%), and participants at elevated risk for cognitive decline. Specifically, 39 of 60 participants (65%) have diabetes, 29 (48.3%) have hypertension, and 13 (21%) report a positive family history of dementia. Data collection will conclude in June 2026, after which data analysis will begin and be completed by September 2026, with primary findings targeted for publication in spring 2027. Conclusions:This protocol investigates the efficacy of B. monnieri (Linn.) in improving cognitive function and altering the blood metabolites in patients with aMCI. If effective, this intervention could provide an accessible and cost-effective approach to manage early AD in resource-limited settings.

BACKGROUND:Deep Brain Stimulation(DBS) of the globus pallidus internus(GPi) is the current surgical standard for medically refractory dystonia; pallidotomy offers a cost-effective alternative. OBJECTIVES:To evaluate clinical outcomes, safety, and radiological correlates of radiofrequency pallidotomy in patients with medically refractory generalised or segmental dystonia. METHODS:Twenty-one patients who underwent unilateral or bilateral radiofrequency pallidotomy (2017-2024) were included in an ambispective analysis. Outcomes were measured using Burke-Fahn-Marsden Dystonia Rating Scale motor(BFMDRS-M) and disability(BFMDRS-D) scores. Post-operative MRI was used to quantify lesion volume and location, and correlations with clinical improvement were analysed. RESULTS:At a mean follow-up of 26.3 ± 21.6 months, BFMDRS-M improved by 35.4 ± 50.4% and BFMDRS-D by 33.1 ± 33.4%. Clinically meaningful improvement (≥30%) was achieved in 66.7% of patients for motor function and 47.6% for disability. Larger total lesion volumes were associated with reduced motor (R = -0.676, p = 0.022) and disability (R = -0.661, p = 0.027) scores; however, this association was no longer present after excluding two patients with disproportionately large lesion volumes. Lesion topography did not correlate with outcomes. Bulbar dysfunction was the most common adverse effect, typically transient. Three patients (14.3%) required further lesioning procedures during follow-up. CONCLUSIONS:In this pilot cohort, pallidotomy appeared to provide clinically meaningful benefit in medically refractory dystonia; however, bulbar adverse effects were frequent underscoring the need for careful patient selection and counselling regarding risk. An association between larger lesion volume and poorer outcome was observed but was driven by two high-volume cases; this preliminary observation requires confirmation in larger, prospective, adequately powered cohorts.

BackgroundAlzheimer's disease (AD) is marked by cognitive decline, depressive symptoms, and gut microbial dysbiosis. Yoga may support cognitive and emotional health while modulating gut microbiota, but integrative clinical evidence is limited.ObjectiveTo evaluate the effects of a 12-week yoga intervention on cognition, depressive symptoms, and gut microbial diversity, composition, and function in Indian patients with mild AD.MethodsIn this hospital-based case-control study, 16 AD patients and 17 cognitively healthy controls (HCs) were recruited at AIIMS, New Delhi. AD diagnosis followed NIA-AA criteria, supported by Montreal Cognitive Assessment (MoCA) and Patient Health Questionnaire-9 (PHQ-9) assessments. AD participants underwent 60-min supervised yoga sessions daily for 12 weeks. Cognitive performance, depressive symptoms, and stool microbiota were assessed pre- and post-intervention. Metagenomic sequencing enabled taxonomic and functional profiling, with alpha diversity, beta diversity (Bray-Curtis distance), and differential abundance analyses performed using standard bioinformatics tools.ResultsYoga was associated with improved cognition (MoCA: 22.33 ± 2.34 → 25.44 ± 2.01; p = 0.001) and reduced depressive symptoms (PHQ-9: 5.78 ± 3.11 → 2.22 ± 1.71; p = 0.007). Alpha diversity remained stable, while beta diversity shifted post-yoga AD samples toward the HC cluster. Beneficial taxa (Faecalibacterium prausnitzii, Roseburia intestinalis, Bifidobacterium, Akkermansia) increased, whereas pro-inflammatory taxa (Collinsella aerofaciens, Klebsiella spp.) decreased. Functional analysis showed partial recovery of metabolic and short-chain fatty acid pathways.ConclusionsA 12-week yoga intervention was associated with cognitive and mood improvements and partial normalization of gut microbial function in mild AD. Larger randomized trials with lifestyle monitoring and multi-omics integration are warranted to confirm causal mechanisms.

Automated cerebrospinal fluid (CSF) biomarkers have been underexplored in early onset dementias (EOD) within the South-Asian context. In our ongoing ASCEND cohort (tertiary care center in India), we evaluated the added value of incorporating CSF amyloid-β 1-42 (Aβ42) and phosphorylated tau 181 (p-Tau181) (Elecsys immunoassay) into existing clinical diagnostic algorithms for EOD. Among 61 participants (mean age: 56.3 ± 5.8 years; 55.7% females), the CSF p-Tau181/Aβ42 ratio revealed alternative etiology in 16% of cases [5/37 (13.5%) clinically probable AD were reclassified as non-AD after CSF, while 5/24 (20.8%) clinically non-AD dementias were reclassified as AD]. Notably, clinico-biological concordance varied across different phenotypic presentations.

Background and Aims: Challenges in stroke care exist at multiple levels. In India, medical colleges are crucial in connecting rural and tertiary care public health systems. Our study aims to implement a uniform stroke care pathway (USCP) and assess its sustainability. Methods: IMPETUS Stroke was a multicentric, prospective, multiphase, mixed method, quasi experimental implementation study conducted at 22 government funded medical colleges to examine the changes in a select set of stroke care related indicators over time. It included a pre-implementation phase (Phase-1), followed by an implementation phase (Phase-2) where residents and nursing officers and caregivers were trained and Phase 3, where the sustainability of the USCP was assessed. Results: Patient recruitment in each phase was n=2,018 (19.8%), n=2,179 (21.3%), and n=5,996 (58.8%). Mean age was 59-years and males were higher. Ischemic stroke constituted the largest proportion (60-62%) in all phases. In phase-2, a total of 2103 residents, 2199 nursing officers and 6038 caregivers were trained. Nine of the 22 sites (40%) established their first-ever stroke units. Key stroke care indicators improved from the phase-1 to phase-3: at admission, NCCT (69.6%, 78.1% and 77.0%), CT-angiograms (18.2%, 25.3% and 38.4%), NIHSS (20.3%, 23.7% and 33.1%), thrombolysis rates (39.2%, 65.8% and 70.7%) (p-trend<0.001). The average door-to-CT time significantly decreased (p-trend<0.001), in-hospital stroke management in select indicators improved significantly (p-trend<0.001), in-hospital mortality decreased from 19.4% to 13.5% (p-trend<0.001) and three-months good functional outcome (mRS:0-2) increased from 41.6% to 46.0% (p-trend<0.001) across the phases. Conclusion: The data presented holds significance in showing the effect of implementation in improving stroke services and patient outcomes.

Introduction Myelin oligodendrocyte glycoprotein-associated disease (MOGAD) is a heterogeneous neuroimmunological disease. Attacks are primarily treated using corticosteroids, with a subset of refractory cases treated with plasma exchange (PLEX). However, the response to PLEX and the optimal timing of its initiation remain uncertain as compared to other disorders. This study evaluates the impact of PLEX and it’s time to initiation on clinical outcomes, as measured by the Expanded Disability Status Scale (EDSS). Materials and Methods All consecutive patients of MOGAD requiring PLEX from January 2019 to July 2023 at a tertiary care centre were included. Inclusion criteria were ages 10-60 with a positive anti-MOG antibody test and use of PLEX due to inadequate steroid response. Exclusion criteria were pseudo-relapse and denial of consent. The primary outcome was the percentage improvement in EDSS at 90 days. Results Among 38 patients with MOGAD, the mean percentage improvement in EDSS at 90 days was 37.7% (SD 28.2). Twenty-three patients (60.5%) achieved ≥33% improvement in EDSS at 90 days. An inverse correlation was observed between time to PLEX and percentage EDSS improvement (p=0.049). In linear regression analysis, each day of treatment delay was associated with a 0.26 percentage point reduction in EDSS improvement. PLEX-related complications occurred in only 7.9% of patients. Conclusion PLEX is effective and safe in MOGAD, but delaying its initiation is associated with reduced clinical improvement, highlighting the importance of early intervention.

IntroductionPopulation-specific normative data are essential for accurately interpreting cognitive test performance, particularly in low-resource settings characterized by low literacy rates. In India, normative values for the Indian Council of Medical Research-Neurocognitive Tool Box (ICMR-NCTB) among older adults in rural communities are limited. The objectives are to generate education-stratified normative values for ICMR-NCTB cognitive domains and to evaluate their cross-sectional classification ability for identifying early cognitive impairment among high-risk older adults in rural India.MethodsBaseline data were derived from the Strategic Multimodal Intervention in at-risk elderly Indians for prevention of dementia (SMRUTHI) cohort, a large, multi-site community-based study conducted across four rural regions of India. Neuropsychological assessments were administered to adults aged 55 years or older using the ICMR-NCTB battery. Normative centiles were estimated using quantile regression and the Box-Cox power exponential (BCPE) method to account for skewness and kurtosis in the test score distributions and to adjust for site effects. Receiver operating characteristic (ROC) analyses assessed the ability of individual tests and composite scores to distinguish normal cognition from early cognitive impairment, as defined by the Clinical Dementia Rating-Sum of Boxes (CDR-SOB).ResultsOf 3,917 individuals pre-screened, 3,000 cognitively normal and 175 cognitively impaired participants were included. Education demonstrated moderate associations with performance, whereas the demonstrated of age and gender were minimal. The normative data demonstrate a steady pattern across older age strata, with stable, domain-specific age-related changes rather than an unexpected decline. Literates performed better than their low-literate counterparts. ROC analyses indicated acceptable to good classification performance for several tests, particularly episodic memory measures and the composite z-score (area under the ROC curves up to 0.84). Empirically derived cutoffs approximated the 25th percentile, striking a balance between sensitivity and specificity for screening purposes.DiscussionThe large-scale, community-based study generated, age-education-stratified normative data for the ICMR-NCTB among high-risk older adults in rural India. The findings underscore the importance of population-specific, percentile-based normative values for early detection of cognitive impairment in settings with low literacy and high cultural diversity, while highlighting limitations related to ceiling effects in certain measures.

Abstract Background Understanding the molecular basis of Parkinson’s disease (PD) phenotypic heterogeneity maybe improved by in vivo access to deep brain tissue. Deep brain stimulation (DBS) surgery offers a unique opportunity: microelectrodes traversing the subthalamic nucleus (STN) carry adherent brain tissue upon withdrawal, providing a source of RNA from subcortical regions in living patients without additional invasive procedures. Aim To develop and validate a low-input RNA extraction and transcriptomic profiling protocol using DBS microelectrodes in post-mortem human brain, to confirm that recovered RNA is of brain rather than blood origin, and to characterise its sub-regional and cellular identity. Methodology DBS microelectrodes were inserted without image guidance or guide tube into three unfixed post-mortem human brains targeting the STN trajectory. In clinical practice, a guide tube shields the electrode from cortical tissue; its absence here means tissue from the full insertion trajectory may contribute to recovered RNA. Thirty-eight microelectrodes were evaluated across single and pooled strategies. RNA was extracted using a modified RNeasy Micro low-input protocol; libraries prepared using NEBNext Single Cell/Low Input RNA Library Kit and sequenced on Illumina NovaSeq 6000 (paired-end, 2×150 bp). Tissue identity was validated against GTEx v10 (54 tissues) and Allen Human Brain Atlas (ABA, 19 subcortical regions including STN) using Pearson correlation with permutation testing (1,000 permutations) and BH-FDR correction. Transcriptional overlap between subcortical and cortical reference regions was quantified and subcortical-enriched gene filtering performed. Results Twenty-five RNA isolates were obtained from 38 microelectrodes; 54.5% of Bioanalyzer-assessed samples achieved RIN ≥5 (median 7.1; range: 5.9-7.8). Fifteen libraries passed sequencing QC (mean depth 43.0 ± 14.1 million read pairs; mean Q30 83.2 ± 5.6 %). PCA of rlog transformed expression data resolved samples by donor identity. All samples confirmed brain tissue origin by GTEx τ-index tissue specificity correlation (n=996 brain and blood specific markers). Brain correlations were highest for frontal cortex (mean r= 0.683 ± 0.072), anterior cingulate cortex (mean r= 0.658 ± 0.069), amygdala (mean r= 0.615 ± 0.068), and basal ganglia including caudate (mean r= 0.553 ± 0.059), putamen (mean r= 0.546 ± 0.059), and nucleus accumbens (mean r= 0.544 ± 0.057); all BH-FDR < 0.05. Cerebellum showed the lowest brain correlations (cerebellar hemisphere: mean r = 0.327 ± 0.039; cerebellum: mean r = 0.314 ± 0.037). Whole blood correlation was strongly negative (mean r= −0.250 ± 0.079), confirming non-haematological origin. ABA genome-wide analysis confirmed positive STN correlation (r=0.54–0.62; permutation p<0.001). MuSiC cell-type deconvolution against the Allen Brain Atlas HMBA-BG snRNA-seq reference identified oligodendrocytes (33.5 ± 17.2%), frontal cortical neurons (9.1 ± 7.0%), STR D1 MSNs (6.0 ± 4.9%), and dopaminergic neurons (1.1± 2.7%) as the principal cell types, independently corroborating bulk transcriptomic findings at single-cell resolution. Conclusion This study validates a low-input RNA extraction protocol for DBS microelectrodes, confirming brain-specific transcriptomic profiles consistent with STN-adjacent subcortical sampling. The 96% transcriptional overlap between cortical and subcortical regions, combined with absence of a guide tube in this post-mortem model, limits sub-regional specificity; clinical application with a guide tube would enrich the subcortical signal. These findings provide the methodological framework for in vivo molecular profiling of the human basal ganglia during DBS surgery in PD patients.

Spinal muscular atrophy (SMA) research has focused predominantly on paediatric populations, with limited adult data from low- and middle-income countries (LMICs). We prospectively recruited suspected SMA patients (age ≥ 12 years) into a neuromuscular disease cohort at a tertiary centre in northern India, using phenotyping, creatine kinase, electrophysiology and genetic testing. Forty genetically confirmed patients were included (median age 20.5 years; mean symptom duration 14.7 ± 10.9 years). Proximal lower-limb weakness was the commonest presentation (82.5%). Forty-five percent were misdiagnosed as muscular dystrophy or congenital myopathy. Three SMA patients received risdiplam. Our cohort highlights the diagnostic challenges of adult SMA and supports a genetics-first approach. Early genetic confirmation shortens diagnostic delay, reduces misclassification and helps eligible patients benefit as disease-modifying therapies become more affordable in resource-limited settings.

Cognitive impairment in type 2 diabetes mellitus affects self-management of the disease, creating a vicious cycle of worsening cognitive and glycaemic control. Low- and middle-income countries are underrepresented in research focusing on this association. This study aimed to evaluate the frequency, severity, spectrum and risk factors associated with cognitive impairment in elderly individuals with diabetes in India. Elderly participants aged 60 years and above underwent a comprehensive clinical, biochemical and neuropsychological evaluation (cognitive concerns, neuropsychological testing and functional activity assessments). A total of 832 participants were included: 698 with diabetes and 134 without diabetes. Participants with diabetes had a mean age of 65.2 ± 4.5 years and average HbA1c level of 7.8 ± 1.8

SMRUTHI-INDIA is a Cohort Multiple Randomized Controlled Trial (cmRCT) study examining risk and protective factors in preventing dementia. Globally, around 50 million adults are diagnosed with dementia, with India accounting for approximately 16% of these cases. Identifying protective factors, such as sleep quality, may help delay or prevent its onset. This study explores the potential protective role of sleep quality in maintaining cognitive health among the elderly. This study employed a cmRCT design, allowing for repeated RCTs within an established cohort. The cohort was formed across four rural zones of India, focusing on dementia risk factors with annual neuropsychological assessments over five years. The current sample includes 2,402 individuals aged 55 and above. Sleep quality and cognition were assessed using the Pittsburgh Sleep Quality Index (PSQI) and Addenbrooke’s Cognitive Examination III (ACE-III). Sex-based comparisons were analysed using the Wilcoxon Rank-Sum test. Of 2,402 participants, 61.62% were females. Based on PSQI scores, 1,981 participants (83%) had good sleep quality (PSQI < 5), where data of 14 females and 10 males was not available due to lack of consent. Among females, 1,183 had good sleep quality; among males, 798 had good sleep quality. Cognitive performance, measured using ACE-III, was compared across sleep quality groups using Wilcoxon Rank-Sum test. In males, poorer sleep quality was significantly associated with lower cognitive scores (p = 0.01). However, no significant association was observed in females (p = 0.7), indicating a potential sex-specific difference in the relationship between sleep quality and cognitive function. The findings of current study suggest that poor sleep quality is significantly associated with reduced cognitive performance in elderly males but not in females, highlighting a possible sex-specific difference in how sleep affects cognitive health. These results underscore the importance of considering gender-specific approaches when designing interventions to preserve cognitive function and potentially prevent dementia in aging populations. Further longitudinal analysis may help clarify the underlying mechanisms and long-term impact of sleep quality on cognitive decline.

Alzheimer's disease is a multifactorial neurodegenerative disorder marked by cognitive decline, synaptic dysfunction, and metabolic alterations. This study investigated disease-associated profiles in the Indian population using integrated clinical, metabolomic, and plasma biomarker analyses. We enrolled 25 clinically diagnosed patients (mean age: 61.20 ± 7.76 years) and 25 cognitively healthy controls (mean age: 60.56 ± 7.48 years). Cognitive and neuropsychiatric assessments included Addenbrooke's Cognitive Examination-III, Clinical Dementia Rating-Global, and Patient Health Questionnaire-9 for patients, and Montreal Cognitive Assessment, Clinical Dementia Rating-Global, and Patient Health Questionnaire-9 for controls. Plasma metabolomics was performed using liquid chromatography-mass spectrometry, and targeted ELISA quantified amyloid beta 40, amyloid beta 42, phosphorylated tau181, phosphorylated tau217, neurofilament light chain, apolipoprotein E, APOE4, 8-hydroxy-2'-deoxyguanosine, C-reactive protein, brain-derived neurotrophic factor, and glutamate. Statistical analyses included principal component analysis, volcano plots, receiver operating characteristic curves, pathway enrichment, and correlation analyses. Patients showed reduced cognition (median Addenbrooke's Cognitive Examination-III: 26). Clinical Dementia Rating-Global scores (1.44 ± 0.65 versus 0.24 ± 0.25; P < 0.0001) and Patient Health Questionnaire-9 scores (4.88 ± 4.21 versus 0.20 ± 0.50; P < 0.0001) were higher than controls. Principal component analysis revealed distinct metabolic clustering with 75 altered metabolites. Volcano analysis identified six upregulated (leucine, ascorbic acid, guanine) and 14 downregulated metabolites (valine, nicotinamide, octadecanedicarboxylic acid). Receiver operating characteristic curves highlighted octadecanedicarboxylic acid (AUC = 0.917), prolinamide (AUC = 0.908), 2-phosphoglycerate (AUC = 0.858), nicotinamide (AUC = 0.848), leucine (AUC = 0.768), and ascorbic acid (AUC = 0.748). Pathway enrichment indicated disruptions in branched-chain amino acid metabolism, nicotinamide metabolism, the tricarboxylic acid cycle, and neurotransmitter pathways. Biomarker analysis revealed elevated amyloid beta 40, amyloid beta 42/40 ratio, phosphorylated tau181, phosphorylated tau217, phosphorylated tau217/amyloid beta 42 ratio, neurofilament light chain, APOE4, C-reactive protein, and 8-hydroxy-2'-deoxyguanosine, with reduced brain-derived neurotrophic factor (all P < 0.05). Significant correlations included eupatilin with phosphorylated tau217 and 8-hydroxy-2'-deoxyguanosine, glyceraldehyde with brain-derived neurotrophic factor, guanine with APOE4, and valine inversely with phosphorylated tau181. This study identifies distinct metabolic (octadecanedicarboxylic acid, prolinamide, leucine, ascorbic acid) and biomarker profiles (phosphorylated tau217, 8-hydroxy-2'-deoxyguanosine, brain-derived neurotrophic factor) in Alzheimer's disease. Disrupted pathways linked to neuroinflammation and oxidative stress support the potential for integrated early detection strategies. Despite the small cross-sectional cohort, findings highlight the need for longitudinal, multi-centric validation.

ABSTRACT:Anti-IgLON5 disease is an evolving entity that lies at the confluence of autoimmunity and neurodegeneration. Reports from India remain sparse. In this series, we describe seven Indian patients with anti-IgLON5-related disease. Patients presented across the fifth to eighth decades with a mean duration of illness of 16 months. All had movement disorders, which included gait ataxia, parkinsonism, and chorea. Six patients had sleep disturbances. Five had a frontal dysexecutive dementia phenotype. Two had epilepsy. Bulbar involvement was present in four, and one had amyotrophic lateral sclerosis (ALS)-like features. Magnetic resonance imaging was abnormal in two cases. Positron emission tomography of the brain also contributed to diagnosis. Combination immunotherapies were used in most of the patients, with three showing a sustained response and two deaths reported due to sepsis-related complications. It is important to recognize the increasing spectrum of IgLON5-related disease to enable timely initiation of immunotherapy before marked degeneration occurs.

SMRUTHI-India is a multimodal initiative to establish a cohort across four sites in India for randomized controlled interventions to prevent dementia in the at-risk elderly population. Dementia prevalence in India is 7.9%, with higher rates in rural than urban areas. Given the high prevalence, low health literacy, and multicultural context, developing relevant print and audiovisual materials for psycho-education tailored to rural populations is essential. The Care Bundle Module (CBM) was developed by a multidisciplinary team at AIIMS, New Delhi focused on the prevention of Dementia in rural population. The CBM Booklet was created and Content Validity Index (CVI) was also calculated based on feedback from five experts. It was then transformed into 10 animated videos in three stages: Pre-Production, Production and Post-Production. To evaluate “understandability” and “actionability” of both the booklet and videos, the Patient Educational Material Assessment Tool (PEMAT) for print (P) and audio-visual (AV) formats was used among 83 (P) and 86 (AV) participants across the sites. Qualitative feedback from the target population and a behavioral expert was also taken and is currently being incorporated into the material. The CBM Booklet’s S-CVI/Avg was 0.933, indicating 93.3% content validity based on expert ratings. PEMAT understandability scores averaged 96.35% (Print) and 95.46% (Audio-Visual), while actionability scores were 97.90% (P) and 98.75% (AV). PEMAT-based CVI showed strong regional agreement: Himachal Pradesh reported S-CVI/Avg of 0.9802 (P) and 0.993 (AV), Kappa 0.98 and 0.993; Karnataka 0.943 (P) and 0.975 (AV), Kappa 0.94 and 0.97; Rajasthan 0.9828 (P) and 0.9791 (AV), Kappa 0.9829 and 0.979; Tripura 0.9921 (P) and 0.9053 (AV), Kappa 0.9921 and 0.902. These results show high I-CVI and Kappa across regions, confirming excellent content validity and inter-rater agreement. The CBM materials demonstrated strong agreement in both experts and target population as reflected in high S-CVI/Avg and Kappa values across regions. PEMAT scores confirmed excellent understandability and actionability in both print and audiovisual formats. These results highlight the relevance and effectiveness of the CBM in delivering dementia-related psychoeducation in rural India.

With the projected surge in dementia cases across low- and middle-income countries, India faces an urgent need for early prevention strategies targeting at-risk populations. The SMRUTHI cohort was developed to characterize dementia risk factors and cognitive health among rural elderly individuals (aged ≥55 years) across diverse Indian regions. This multicentric, cross-sectional study recruited 2,402 participants across four rural regions: Tripura (East), Rajasthan (West), Karnataka (South), and Himachal Pradesh (North). Trained field investigators and psychologists conducted home visits and collected data using validated Case Report Forms (CRFs) via the REDCap platform. A dedicated data management team performed daily checks to ensure completeness and consistency. Participants were classified as illiterate if they were unable to read and write a short, simple statement related to daily life. Missing data were minimized through mandatory REDCap fields, planned revisits, and reassurances about confidentiality. Multiple imputation by chained equations (MICE) was planned for any remaining missing data. Monthly backups were done by the central statistician to ensure data security. Blinding was maintained; outcome assessors and the statistical analyst remained unaware of group allocation during analysis. Among the 2,402 participants, most were aged ≥60 years (75.4–81.5%), and females comprised 58–66% across sites. Illiteracy was highest in Tripura (81.8%) and Karnataka (77.8%). Hypertension and diabetes were observed in up to 40.2% and 16.6%, respectively. Smoking (41.1%) and alcohol use (41.3%) were highest in Tripura. High adherence to the MIND diet was found in 97.3% in Tripura, but only 17.9% in Rajasthan. Low physical activity (<600 MET-min/week) was most common in Karnataka (58.6%). PHQ-9 scores showed depressive symptoms ≥5 in up to 9.7% (Karnataka); non-zero medians ranged from 1 (Himachal) to 6 (Tripura). Median ACE-III scores varied by region: Tripura 78 (95% CI: 77–80), Rajasthan 84 (83–85), Karnataka 88 (88–89), and Himachal 87 (87–88). The SMRUTHI cohort provides critical baseline data on dementia risk in rural India, highlighting the need for region-specific, multidomain prevention strategies in low-resource settings.