Effect of early menopause on cognition and brain morphology in an Urban Indian Cohort.

BACKGROUND: Evidence for the effect of early menopause on cognition among older women is not consistent and is scant among the Indian population. METHODS: We aimed to examine the effect of early menopause (≤45 years) on cognitive performance and brain morphology among older dementia-free females of the TLSA cohort using a multiple linear regression analysis. RESULTS: In a sample of 528 women, 144 (27%) had early menopause. The linear regression analysis showed that women with early menopause performed poorly in cognition and had lesser total gray matter volume [ß = -11973.94, p = 0.033], left middle frontal [ß = -353.14, p = 0.033], and left superior frontal [ß = -460.97, p < 0.026] volume. CONCLUSION: Dementia-free women with early menopause had poorer cognition, lower total gray matter, and frontal lobe. More research is needed to explore the link between earlier menopause and cognitive decline and develop ways to address it. HIGHLIGHTS: Evidence on the effect of early menopause on brain morphology is inconsistent and scant in low and middle-income countries, such as India. In a cohort of dementia-free individuals in urban Bangalore, we observed that participants with early menopause had significantly lower cognitive performance and lower total gray matter and frontal lobe volume. We recommend increasing awareness of this fact among the medical community and the general public. There is an urgent need to explore the underlying biological mechanism and to discover effective interventions to mitigate the effect.

Alteration in amygdala subfield volumes and their association with cognition in mild cognitive impairment.

BACKGROUND: The amygdala has an important role in cognitive and affective functions. The involvement of amygdala and related limbic structures is implicated in many aspects of memory and emotion in mild cognitive impairment (MCI). In the present study, we aimed to compare the volumetric measurements of amygdala and its subfields as well as their association with cognitive functions in stable MCI (sMCI). METHODS: We performed Addenbrooke's cognitive examination III (ACE-III) test, as well as high-resolution T1-weighted images from 31 participants with sMCI and 31 age-matched healthy controls. The amygdala subfield volumes were extracted using Freesurfer software, and group differences were assessed using general linear model (GLM) with age, gender, education and estimated intracranial volume (ICV) as covariates. Partial correlation was also calculated between cognitive scores and volumes of amygdala subfields in healthy controls and sMCI participants controlling for estimated ICV. RESULTS: sMCI participants exhibited significantly reduced volumes in most of the right amygdala subfields, including basal nucleus, accessory basal nucleus, central nucleus, medial nucleus, corticoamygdaloid transition area, and whole amygdala, as well as significantly reduced right amygdala/hippocampus ratio compared to healthy controls. In addition, our results revealed statistically significant positive correlations between ACE memory scores and the volumes of right central nucleus, right medial nucleus, right cortical nucleus, and the right whole amygdala, in sMCI. CONCLUSIONS: Our findings revealed volumetric reductions in most of the right amygdala subfields along with its association with the memory functions in sMCI. These findings provide valuable insights into the underlying anatomical factors contributing to neurocognitive symptoms in MCI.

The 2022 symposium on dementia and brain aging in low- and middle-income countries: Highlights on research, diagnosis, care, and impact.

Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.

Music and the aging brain - Exploring the role of long-term Carnatic music training on cognition and gray matter volumes.

Objectives: Aging is a natural process and is often associated with an increased incidence of cognitive impairment. Physical exercise, diet, and leisure activities (music, dance, and art) are some of the lifestyle factors that contribute to healthy aging. The present study aims to explore the differences in cognitive functioning between aging individuals involved in musical activity throughout their lifetime and the ones who were not. Materials and Methods: Fifty-one healthy elderly individuals (50-80 years of age) residing in an urban locality were selected for the study from the Tata Longitudinal Study of Aging cohort. Participants were divided into two groups: Active musicians trained in Carnatic music for more than five years (n = 18) and age-matched non-musicians (n = 33). Addenbrooke cognitive examination-III, Hindi mental status examination, and trail-making test-B (TMT-B) were used to assess cognitive functioning. A Generalized Linear Regression Model was performed including covariates such as gender, age, and years of education. We also looked at the available brain magnetic resonance imaging data of a subset of our study population to inspect the volumetric differences between musicians and non-musicians. Results: Our results showed that musicians had significantly better visuospatial abilities as compared to non-musicians (P = 0.043). Musicians (130.89 ± 45.16 s) also took less time to complete the TMT-B task than non-musicians (148.73 ± 39.65 s), although it was not a statistically significant difference (P =0.150). In addition, brain imaging data suggested that musicians had increased gray matter volumes in the right precuneus, right post-central gyrus, right medial and superior frontal gyrus, right orbital gyrus, left middle temporal gyrus, left cuneus, left fusiform gyrus, and bilateral cingulate gyrus. Conclusion: Our findings are indicative of music being an important attribute in improving cognitive reserve and predicting cognitive resilience. These findings pave the way to explore the utility of non-pharmacological interventions, such as Music Therapy (especially Carnatic music in the Indian context), as a potential factor for improving cognitive reserve in elderly individuals.

Transcranial direct current stimulation-efficacy in mild cognitive impairment: A meta-analysis.

Objectives: Mild cognitive impairment (MCI) is a transition state in which individuals have cognitive abilities that are in between those of normal aging and dementia. Although not everyone with MCI develops dementia, the risk of progression to dementia is higher in people with MCI. Interventions at this stage can prevent or delay the onset of dementia. In recent years, studies on non-invasive brain stimulation techniques, namely transcranial direct current stimulation (tDCS), have gained momentum for cognitive enhancement in MCI. Since there are very few studies that also report varied results, it becomes important to analyze the effect of tDCS in MCI. The aim of this study was to systematically review the available evidence about using tDCS for MCI and to assess its efficacy using meta-analysis. Materials and Methods: Eight single- or double-blinded randomized controlled trials were included in the study. Montreal cognitive assessment (MoCA) and mini-mental state examination (MMSE) for global cognition; and digit span test forward and backward, trail-making test (TMT) A and B; and logical memory test (LMT) assessing specific cognitive domains were considered. A random-effects model was used wherein the standardized mean difference (SMD) and its 95% confidence intervals were reported. Results: The effect of the active tDCS (MoCA [SMD 0.37, 95% CI -0.22-0.95], MMSE [SMD 0.26, 95% CI 0.25-0.77], TMT-A [SMD -0.01, 95% CI -0.42-0.40], and LMT [SMD 0.80, 95% CI -0.24-1.83]) when compared with the sham tDCS was statistically insignificant. Conclusion: The current meta-analysis identified insignificant improvement in cognitive performance with active tDCS treatment as compared to sham tDCS among people with MCI.

Prevalence and patterns of vitamin D deficiency and its role in cognitive functioning in a cohort from South India.

Vitamin D (VitD) is a naturally occurring, fat-soluble vitamin which regulates calcium and phosphate homeostasis in the human body and is also known to have a neuroprotective role. VitD deficiency has often been associated with impaired cognition and a higher risk of dementia. In this study, we aimed to explore the relationship between levels of VitD and cognitive functioning in adult individuals. 982 cognitively healthy adults (≥ 45 years) were recruited as part of the CBR-Tata Longitudinal Study for Aging (TLSA). Addenbrooke's cognitive examination-III (ACE-III) and Hindi mental status examination (HMSE) were used to measure cognitive functioning. 25-hydroxyvitamin D [25(OH)D] levels were measured from the collected serum sample and classified into three groups- deficient (< 20 ng/ml), insufficient (20-29 ng/ml) and normal (≥ 30 ng/ml). Statistical analysis was done using IBM SPSS software, version 28.0.1.1(15). The mean age of the participants was 61.24 ± 9 years. Among 982 participants, 572 (58%) were deficient, 224 (23%) insufficient and only 186 (19%) had normal levels of VitD. Kruskal-Wallis H test revealed a significant difference in age (p = 0.015) and education (p = 0.021) across VitD levels and the Chi-square test revealed a significant association between gender (p = 0.001) and dyslipidemia status (p = 0.045) with VitD levels. After adjusting for age, education, gender and dyslipidemia status, GLM revealed that individuals with deficient (p = 0.038) levels of VitD had lower scores in ACE-III verbal fluency as compared to normal. Additionally, we also found that 91.2% individuals who had VitD deficiency were also having dyslipidemia. It is concerning that VitD deficiency impacts lipid metabolism. Lower levels of VitD also negatively impacts verbal fluency in adult individuals. Verbal fluency involves higher order cognitive functions and this result provides us with a scope to further investigate the different domains of cognition in relation to VitD deficiency and other associated disorders.

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.

Treatment strategies for serotonin reuptake inhibitor-resistant obsessive-compulsive disorder: A network meta-analysis of randomised controlled trials.

OBJECTIVES: Treatment-resistant obsessive-compulsive disorder is a chronic debilitating illness. We conducted a network meta-analysis [NMA] to compare the efficacy of all interventions in SRI-resistant OCD from published Randomised controlled trials [RCT]. METHODS: We performed an NMA of RCTs in SRI resistant OCD from all modalities of treatments; pharmacological, psychological, neuromodulation, neurosurgery including deep brain stimulation. The design-by-treatment interaction inconsistency model within the frequentist framework was adopted with a change in Yale-Brown Obsessive-Compulsive Scale score as the primary outcome. We conducted sensitivity analyses excluding studies examining neurosurgical interventions, deep brain stimulation, studies in the paediatric population, and studies from a single geographical region. We also conducted analyses of interventions categorised into treatment groups. RESULTS: 55 RCTs examining 19 treatments or placebo involving 2011 participants were included in the NMA. Ondansetron [Standardised mean difference -2.01 (95% CI: -3.19, -0.83)], deep TMS [- 1.95 (-3.25, -0.65)], therapist administered Cognitive Behavioural Therapy [CBT-TA] [-1.46 (-2.93, 0.01)] and aripiprazole [-1.36 (-2.56, -0.17)] were ranked as the best four treatments on using the Surface Under the Cumulative Ranking [SUCRA] percentage values (85.4%, 83.2%, 80.3%, 67.9% respectively). While all four interventions had large effect sizes, CBT[TA] narrowly missed statistical significance in our analysis. In sensitivity analyses, deep TMS was ranked as the best treatment strategy for SRI-resistant OCD. The small number of subjects in individual studies, higher confidence interval limits, and wider prediction interval for most agents warrant a cautious interpretation. CONCLUSIONS: Considering the principal analysis and sensitivity analyses together, deep TMS, ondansetron, CBT[TA], and aripiprazole may be considered a first-line intervention for SRI-resistant OCD in adults. OTHER: This work was not funded. The NMA has been registered with PROSPERO, [Registration number: CRD42020173589].

Reflected image processing abnormalities in dementia - a case series and review.

Dementia is a neurodegenerative condition with progressive decline in cognitive faculties and associated with different clinical phenomena. Mirror phenomenon in terms of both mirror agnosia and mirror image agnosia wherein there is difficulty in processing and perception of reflected images is not uncommonly seen, and understanding the same can contribute to early diagnosis and prognostication. We report two elderly women with Alzheimer's dementia and frontotemporal dementia, respectively, presenting with features of abnormalities in mirror image processing. The former had features of both mirror agnosia and mirror image agnosia and the latter had predominantly features of mirror image agnosia with preoccupation with her mirror image. Understanding neuroanatomical networks underlying these phenomena can help early identification and subtyping dementia. Clinically differentiating these phenomena from psychotic symptoms of dementia can help in initiating appropriate non-pharmacological measures rather than resorting to use of psychotropics, the use of which may be counterproductive.

Companionship and Sexual Issues in the Aging Population.

Loneliness and social isolation are significant public health crises in older adults. The issues about companionship have many psychosocial and cultural dimensions, which is further compounded by the current COVID-19 pandemic. In modern-day India, there is a significant increase in the number of older adults left to live alone because of sociocultural changes in our society. Companionship in late life is known to promote the quality of life and decrease the mental health morbidity. There is an increasing role of pets as companions to the elderly. Novel technologies such as artificial intelligence in the form of robots are being explored to support the elderly. Sexuality is another complex issue related to older adults that is often ignored. The sexuality and sexual functioning in older adults largely depend on physiological, psychological, and sociocultural factors. The principles of ageism have influenced sexuality in older adults. Sociocultural issues and the aging-related pathophysiological changes can contribute to an increased risk for legal issues related to sexuality in this population. There is a need for more systematic research into the multifaceted concept of companionship and sexuality in the older adult population. This review article addresses these two distinct subjects separately.

Maintenance and Welfare of Parents and Senior Citizens Act 2007: A Critical Appraisal.

BACKGROUND: The sociocultural changes associated with globalization and development have weakened the traditional values and family support systems for senior citizens (age 60 years and above). There is an increase in the prevalence of elder abuse and difficulties in getting appropriate care and support. This has mandated legal measures to protect the rights of the senior citizens and provide them care and support by the family and other stakeholders. Consequent to being the signatory for the "Madrid International Plan of Action on Ageing, 2002," several countries, including India, have introduced legislation for the social protection of senior citizens. "The Maintenance and Welfare of Parents and Senior Citizens(MWP) Act, 2007" is an important legislation in India to safeguard the elderly from exploitation and abuse. METHODS: This article critically evaluates the implementation of the MWP Act, 2007, and the related challenges in protecting senior citizens from abuse. The article will also highlight the proposed amendments in the Act to strengthen the effective implementation of legal protection for senior citizens and ensure their well-being and dignity. CONCLUSIONS: The MWP act is an important legal measure to ensure mainatinence and welfare of senior citizens and protect them from abuse and neglect. There is an immediate need to incorporate the necessary amendments so that the act gets more pragmatic value and becomes and important tool for elderly care and protection and reduce vulnerabilities and ensure holistic care with support in various bio-psycho-social domains.