Mary Ganguli

University of Pittsburgh | Pitt · Department of Medicine

Background Many complex traits and diseases show sex‐specific biases in clinical presentation and prevalence. For instance, two‐thirds of AD cases are female. Studies suggest that women might have higher cognitive reserve but steeper cognitive decline in older age. Cognitive traits have substantial genetic influence. Cognitive impairment could vary...

Background The relationship between subtle cognitive decline and Alzheimer's disease (AD) pathology as measured by biomarkers in settings outside of specialty memory clinics is not well characterized. Objective To investigate how subtle longitudinal cognitive decline relates to neuroimaging biomarkers in individuals drawn from a population-based s...

Background The associations between community‐wide social determinants of health and mild cognitive impairment (MCI) among individuals warrant investigation. Methods Among 2830 dementia‐free individuals aged 65+ years in a community‐based US study, we examined cross‐sectional associations of MCI (Clinical Dementia Rating = 0.5) with the following...

Background Blood-based biomarkers are gaining grounds for the detection of Alzheimer’s disease (AD) and related disorders (ADRDs). However, two key obstacles remain: the lack of methods for multi-analyte assessments and the need for biomarkers for related pathophysiological processes like neuroinflammation, vascular, and synaptic dysfunction. A nov...

Importance Poststroke cognitive impairment is common, but the cognitive trajectory following a first stroke, relative to prestroke cognitive function, remains unclear. Objective To map the trajectory of cognitive function before any stroke and after stroke in global cognition and in 4 cognitive domains, as well as to compare the cognitive trajecto...

Background Cardiometabolic multimorbidity (CMM) and depression are often co-occurring in older adults and associated with neurodegenerative outcomes. The present study aimed to estimate the independent and joint associations of CMM and depression on cognitive function in multi-regional cohorts, and to validate the generalizability of the findings i...

Background: Blood-based biomarkers are gaining grounds for Alzheimer's disease (AD) detection. However, two key obstacles need to be addressed: the lack of methods for multi-analyte assessments and the need for markers of neuroinflammation, vascular, and synaptic dysfunction. Here, we evaluated a novel multi-analyte biomarker platform, NULISAseq CN...

INTRODUCTION Plasma biomarkers of Alzheimer's disease and related dementias predict global cognitive performance and decline over time; it remains unclear how they associate with changes in different dementia syndromes affecting distinct cognitive domains. METHODS In a prospective study with repeated assessments of a randomly selected population‐b...

Background Identifying potentially modifiable risk factors associated with MCI in different ethnoracial groups could reduce MCI burden and health inequity in the population. Methods Among 2845 adults aged 65+ years, we investigated potential risk exposures including education, physical and mental health, lifestyle, and sensory function, and their...

Introduction Enrolling individuals from underrepresented ethnoracial groups in aging research is often a challenge. Methods We sought a diverse sample of older adults from a small-town area for a longitudinal aging study. We employed an intensive community engagement approach encompassing a range of recruitment strategies. Results Over 4 years a...

INTRODUCTION The LIfestyle for BRAin Health (LIBRA) index yields a dementia risk score based on modifiable lifestyle factors and is validated in Western samples. We investigated whether the association between LIBRA scores and incident dementia is moderated by geographical location or sociodemographic characteristics. METHODS We combined data from...

Objectives There is a paucity of population‐level data on marijuana use and mental health and functioning in older adults. Methods We analyzed cross‐sectional data ( n = 910) from a well‐characterized cohort, the Monongahela‐Youghiogheny Healthy Aging Team (MYHAT) study. MYHAT is an age‐stratified random sample of the population age 65 years and o...

Introduction India, with its rapidly aging population, faces an alarming burden of dementia. We implemented DSM-5 criteria in large-scale, nationally representative survey data in India to characterize the prevalence of mild and major Neurocognitive disorder. Methods The Harmonized Diagnostic Assessment of Dementia for the Longitudinal Aging Study...

Background:Good social connections are proposed to positively influence the course of cognitive decline by stimulating cognitive reserve and buffering harmful stress-related health effects. Prior meta-analytic research has uncovered links between social connections and the risk of poor health outcomes such as mild cognitive impairment, dementia, an...

Objective:Health disparities between communities with greater and lesser advantages are a global concern. In the USA, self-identified race as African American (AA) is consistently associated with mild cognitive impairment (MCI) and dementia, compared to Americans of European descent. In a prospective population-based study, we sought to confirm thi...

A 2013 systematic review and Delphi consensus study identified 12 modifiable risk and protective factors for dementia, which were subsequently merged into the “LIfestyle for BRAin health” (LIBRA) score. We systematically evaluated whether LIBRA requires revision based on new evidence. To identify modifiable risk and protective factors suitable for...

Background Hippocampal formation atrophy is a well‐established imaging biomarker of several neurological diseases, including Alzheimer’s disease, temporal lobe epilepsy, and schizophrenia. The hippocampus is divided into subfields that have different functions and vary in sensitivity to different diseases. This study investigates the potential inte...

Background The long‐term impact of COVID‐19 on global health is still unknown. Sensorimotor biomarkers may be promising indicators of lasting effects of COVID‐19. Although normal aging may cause changes in sensorimotor function, more severe changes may indicate the subsequent impacts of COVID‐19 on brain health. The objective of this study was to i...

Background Globally, over six hundred million cases of SARS‐CoV‐2 have been confirmed. As the number of individuals in recovery rises, examining long‐term neurological effects, including cognitive impairment and cerebral microstructural and microvascular changes, has become paramount., We present preliminary cognitive findings from an ongoing multi...

Background A significant percentage of Aβ‐positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, cognitive decline.Experimental literature suggest that reactive astrocytes are necessary to unleashing Aβ effects in pathological tau phosphorylation.Here we aimed to investigate whether as...

Background Depression is a known risk factor for dementia, and social support may lower the risk of depression in older adults. There is, however, a lack of longitudinal analyses examining the association between emotional versus instrumental support and depressive symptoms in older adults. We analyzed the association of emotional and instrumental...

Background The COVID‐19 pandemic has disproportionately affected ethno‐racial minority populations and people with greater social deprivation. It is unknown whether such disparities influence research participation for investigations of long‐term neuro‐cognitive effects of SARS‐CoV‐2 infection. Method Across 3 US and 1 UK sites, we are enrolling a...

Background Emerging evidence indicates that COVID‐19 can negatively impact patient’s brain health (Douaud et al., 2022) (Cecchetti et al., 2022). Common clinical symptoms include brain fog, headaches, difficulty concentrating, and loss of sense of smell or taste. Some studies suggest that SARS‐CoV‐2 infection can damage the blood brain barrier eith...

Background A significant percentage of Aß‐positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, cognitive decline.Experimental literature suggest that reactive astrocytes are necessary to unleashing Aß effects in pathological tau phosphorylation.Here we aimed to investigate whether as...

The effect of the COVID-19 pandemic on older adults’ mental health is especially salient given their increased vulnerability to the pathologic and social effects of both the disease and also the associated mitigation strategies. The purpose of this research is to examine trends in symptoms of depression and anxiety among older adults during two pha...

INTRODUCTION Detection of Alzheimer's disease (AD) pathophysiology among individuals with mild cognitive changes and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma phosphorylated tau 217 (p‐tau217) is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited. METHODS We...

INTRODUCTION Detection of Alzheimer’s disease (AD) pathophysiology among cognitively unimpaired individuals and those experiencing subjective cognitive decline (SCD) remains challenging. Plasma p-tau217 is one of the most promising of the emerging biomarkers for AD. However, accessible methods are limited. METHODS We employed a novel p-tau217 immu...

Introduction: India, with its rapidly aging population, faces an alarming burden of dementia. We implemented DSM-5 criteria in large-scale, nationally representative survey data in India to characterize the prevalence of mild and major Neurocognitive disorder. Methods: The Longitudinal Aging Study in India's Diagnostic Assessment of Dementia (LASI-...

In this study, we examined associations of social isolation and loneliness with cognitive impairment among older adults from a Rust Belt region in Southwest Pennsylvania. We used data from the population-based Monongahela-Youghiogheny Healthy Aging Team (MYHAT) study. We found that (a) 11 items combined into two reliable composites of social isolat...

Background A rare missense APOE variant (L28P; APOE * 4Pittsburgh) has been reported to be a risk factor for Alzheimer’s disease (AD). However, sinceL28P has been observed only among APOE * 4 carriers, its independent genetic association is uncertain. In this study, we re‐evaluated this association in a large case‐control sample of 15,762 U.S. Whit...

Background Although accumulating evidence has shown that individual socioeconomic status affects dementia incidence, it remains unknown whether a higher degree of neighborhood disadvantage which is independent of individual socioeconomic status contributes to the excess risk of dementia among African Americans (AA). Method In the Monongahela‐Yough...

Background Most previous studies of amyloid[A], tau[T], and/or neurodegeneration[(N)] prevalence have been completed in highly selected samples, leaving low SES older adults from medically underserved areas underrepresented in research. Furthermore, women consistently have greater T and sometimes greater A accumulation than men, but clear character...

An unresolved question for the understanding of Alzheimer’s disease (AD) pathophysiology is why a significant percentage of amyloid-β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes unleash Aβ effec...

Objectives: Older adults commonly take benzodiazepines (BZDs) that may have long-term adverse cognitive effects. We investigated whether BZD use was related to developing mild cognitive impairment (MCI) or dementia in cognitively normal older adults in the community. Setting/participants: A population-based cohort (n = 1959) of adults aged 65 an...

Introduction: Previous meta-analyses have linked social connections and mild cognitive impairment, dementia, and mortality. However, these used aggregate data from North America and Europe and examined a limited number of social connection markers. Methods: We used individual participant data (N = 39271, Mage = 70.67 (40-102), 58.86% female, Med...

Introduction: Cognitive abilities have substantial heritability throughout life, as shown by twin- and population-based studies. However, there is limited understanding of the genetic factors related to cognitive decline in aging across neurocognitive domains. Methods: We conducted a meta-analysis on 3045 individuals aged ≥65, derived from three...

Introduction: Plasma biomarkers-cost effective, non-invasive indicators of Alzheimer's disease (AD) and related disorders (ADRD)-have largely been studied in clinical research settings. Here, we examined plasma biomarker profiles and their associated factors in a population-based cohort to determine whether they could identify an at-risk group, in...

Objective: To investigate the relationship between anxiety and mild cognitive impairment (MCI), and whether it is mediated by perceived stress, at the population level. Method and design: In a longitudinal study of 368 adults aged 65+ from a population-based cohort, we annually assessed anxiety symptoms (GAD-7), perceived stress (PSS-4), and rat...

Introduction: Sex differences in dementia risk, and risk factor (RF) associations with dementia, remain uncertain across diverse ethno-regional groups. Methods: A total of 29,850 participants (58% women) from 21 cohorts across six continents were included in an individual participant data meta-analysis. Sex-specific hazard ratios (HRs), and wome...

An unresolved question for the understanding of Alzheimer’s disease (AD) pathophysiology is why a significant percentage of amyloid β (Aβ)-positive cognitively unimpaired (CU) individuals do not develop detectable downstream tau pathology and, consequently, clinical deterioration. In vitro evidence suggests that reactive astrocytes are key to unlea...

Objective: We investigated whether anticholinergic drug use was related to developing mild cognitive impairment (MCI) or dementia in older adults at the population level. Methods: We used an Anticholinergic Rating (ACR) scale, Clinical Dementia Rating, APOE genotype, and number of prescription medications. We examined time to incident MCI and in...

Background: Changes in physical health and cognition during aging can result in some older adults to stop driving. In this population-based longitudinal study, we describe potential predictors of driving cessation in older adults. Methods: Age-stratified random population cohort of 1982 adults aged 65 years and older drawn from voter registratio...

Introduction: Prior estimates of dementia prevalence in India were based on samples from selected communities, inadequately representing the national and state populations. Methods: From the Longitudinal Aging Study in India (LASI) we recruited a sample of adults ages 60+ and administered a rich battery of neuropsychological tests and an informa...

The Social Health and Reserve in the Dementia patient journey (SHARED) project is an international collaboration investigating the association between social health and cognitive function. We conducted an individual participant‐level meta‐analysis of the associations between social health variables and cognitive function (global cognition, memory,...

Cognition is a highly complex polygenic trait. A limited number of studies have explored the genetic basis of cognitive decline in aging populations using cognitive domain specific measures. To identify genetic markers for cognitive decline, we conducted a genome‐wide association meta‐analysis and gene‐based tests on five different cognitive domain...

Genome‐wide association studies (GWAS) have identified more than 40 genetic loci associated with Alzheimer’s disease (AD). Although vascular dementia (VaD) is the second most common type of dementia after AD, the genetic contribution to VaD is understudied. We hypothesize that common forms of dementia will share genetic risk factors. We conducted t...

Objectives The restrictions put in place in 2020 to mitigate the spread of the coronavirus disease 2019 limited or eliminated social connections that are vital for psychosocial well-being. The objectives of this research were to examine the impact of early pandemic-related restrictions on feelings of loneliness, depression, and anxiety as well as s...

A rare missense APOE variant (L28P; APOE*4Pittsburgh), which is present only in populations with European ancestry, has been reported to be a risk factor for late-onset Alzheimer's disease (LOAD). However, due to the complete linkage disequilibrium of L28P with APOE*4 (C112R), its independent genetic association is uncertain. The original associati...

Dementia is multifactorial with Alzheimer (AD) and vascular (VaD) pathologies making the largest contributions. Genome-wide association studies (GWAS) have identified over 70 genetic risk loci for AD but the genomic determinants of other dementias, including VaD remain understudied. We hypothesize that common forms of dementia will share genetic ri...

Background Poor social connections (eg, small networks, infrequent interactions, and loneliness) are modifiable risk factors for cognitive decline. Existing meta-analyses are limited by reporting aggregate responses, a focus on global cognition, and combining social measures into single constructs. We aimed to investigate the association between so...

Epidemiology is the foundation of all public health research and practice. Epidemiology confers many important uses for the advancement of neuroimaging research. Epidemiology serves as a framework to organize pieces of data and guide critical thinking in the research process from the early stages of study design to the end goal of reaching appropri...

Introduction Social cognition is the cognitive domain that processes social information, the means by which we make sense of ourselves in relation to others and our environments. Impaired social cognition is associated with functional dependence on others and can have dire social consequences leading to social isolation, increasing the risk for mor...

Objectives: In a population-based study of mild cognitive impairment (MCI), to validate the assessment of social cognition in older adults. Methods: Cross-sectional study of 902 adults aged 65+ with mean age 76.6 years (SD 8.06). We created a social cognition composite comprising standardized z scores on the Social Norms Questionnaire and the 10...

Introduction: Though consistent evidence suggests that physical activity may delay dementia onset, the duration and amount of activity required remains unclear. Methods: We harmonized longitudinal data of 11,988 participants from 10 cohorts in eight countries to examine the dose-response relationship between late-life physical activity and incid...

Objective Emerging evidence suggests low vision may be a modifiable risk factor for cognitive decline. We examined effects of baseline visual acuity (VA) on level of, and change in, cognitive test performance over 9 years. Method A population-based sample of 1,621 participants (average age 77 years) completed a comprehensive neuropsychological eva...

Background Consistent evidence suggested that physical activity (PA) may delay dementia onset. However, the dose‐response association between PA and dementia remains unclear. This study aimed to examine the association between the volume, duration, and intensity of PA and incident dementia among older adults across diverse geographic regions. Meth...

Background Cognitive decline is a major characteristic of aging and neurogenerative diseases such as Alzheimer’s disease (AD), Parkinson’s disease and other dementias. With worldwide increases in life‐expectancy and elderly population, cognitive decline is a major public health concern. Understanding genetic contributors to age‐related decline in c...

Background Memory clinics have historically driven case‐definition, clinical diagnostic criteria, and treatment trials in Alzheimer’s disease and related disorders (ADRD) and investigated neuroimaging and molecular factors leading to the development of ADRD biomarkers. The Uniform Data Set (UDS) of the National Alzheimer’s Coordinating Center (NACC...

Background: Education and occupational complexity are main sources of mental engagement during early life and adulthood respectively, but research findings are not conclusive regarding protective effects of these factors against late-life dementia. Objective: This project aimed to examine the unique contributions of education and occupational co...

Objective: To synthesise international findings on the alcohol-dementia relationship and provide a cross-national comparison of the alcohol-dementia relationship with critical evidence for the relationship between alcohol use and dementia in under-studied populations. Design and setting: Individual participant data meta-analysis of 15 prospective e...

A true understanding of the distribution and functional correlates of Alzheimer’s disease pathology in dementia-free older adults requires a population-based perspective. Here we report initial findings from a sample of 102 cognitively unimpaired participants (average age 77.2 years, 54.9% women, 13.7% APOE*4 carriers) recruited for neuroimaging fr...

Introduction Driving is a key and complex instrumental activity of daily living that requires integration of multiple domains including cognitive, motor, visual and sensory functions in order to perform adequately. Older drivers comprise 19 percent of licensed drivers in the US and 70-80 % of drivers over 75 were considered at fault in two vehicle...

Introduction Social cognition indicates the cognitive processes involved in perceiving, interpreting, and processing social information. It is increasingly recognized in neurocognitive disorders, and it is included in DSM-5 as one of the six core cognitive domains to be assessed for the diagnosis of neurocognitive disorders. However, unlike other c...

Background/objective: Poor air quality is implicated as a risk factor for cognitive impairment and dementia. Few studies have examined these associations longitudinally in well-characterized population-based cohorts with standardized annual assessment of both mild cognitive impairment (MCI) and dementia. We investigated the association between est...

Objectives: To describe factors associated with driving history, habits, and self-reported driving difficulties of 1982 older adults in a population-based survey. Setting: This was a community setting. Participants: Age-stratified random population sample drawn from publicly available voter registration list. Design: Participants underwent a...

Background Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer’s disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Methods We combined individual participant data for 16 cohorts from 15 countries (member...

Background Social cognition indicates the cognitive processes involved in perceiving, interpreting, and processing social information. Although it is one of the six core DSM-5 cognitive domains for diagnosing neurocognitive disorders, it is not routinely assessed in older adults. The Reading the Mind in the Eyes Test assesses Theory of Mind, the so...

Background The pandemic of SARS‐CoV‐2 is focusing all energies on the impact on survival of affected individuals, treatment and prevention, but increasingly attention is focusing on its enduring consequences. We established a global consortium to study a longitudinal representative cohort of individuals, to characterize neurological and neuropsychi...

Background Social isolation and loneliness have detrimental effects on the health of older adults. Being socially isolated and lonely are likely both predictors and consequences of cognitive impairment with aging. However, isolation and loneliness may be differentially associated with cognitive impairment and may operate through both shared and uni...

Background The majority of people with dementia in the population have mixed neurodegenerative and cerebrovascular pathology. Stroke and dementia share many risk factors, and both have potential to impair function and quality of life. Therefore, a comprehensive understanding of vascular brain and cognitive health should integrate stroke and dementi...

Background Recently developed immuno‐precipitation mass spectrometry (IP‐MS) assays to measure blood‐based amyloid‐β with high accuracy holds exciting potential. Adoption of amyloid‐β measurement will be especially valuable in large population studies where not previously feasible. We evaluated the correspondence between a new IP‐MS assay developed...

Objectives To investigate functional health literacy and its associated factors among older adults drawn from a disadvantaged area. Design Cross-sectional epidemiologic study. Setting Population-based cohort randomly selected from the voter registration lists. Participants 1066 individuals aged 65+ years. Measurements The Short Test of Function...

Introduction: Although exercise is associated with a lower risk for mild cognitive impairment (MCI), it is unclear whether its protective effect depends on the presence or absence of vascular factors. Methods: In an exploratory study of data from a population-based cohort, 1254 participants aged 65+ years were followed for 10 years for incident...

Introduction: Depression commonly accompanies Alzheimer's disease, but the nature of this association remains uncertain. Methods: Longitudinal data from the COSMIC consortium were harmonized for eight population-based cohorts from four continents. Incident dementia was diagnosed in 646 participants, with a median follow-up time of 5.6 years to d...

Background: Dementia shows sex difference in its epidemiology. Childbirth, a distinctive experience of women, is associated with the risk for various diseases. However, its association with the risk of dementia in women has rarely been studied. Methods: We harmonized and pooled baseline data from 11 population-based cohorts from 11 countries ove...

Background: Incidence of dementia increases exponentially with age; little is known about its risk factors in the ninth and 10th decades of life. We identified predictors of dementia with onset after age 85 years in a longitudinal population-based cohort. Methods: On the basis of annual assessments, incident cases of dementia were defined as tho...

The genetics of late-onset Alzheimer's disease (AD) is complex due to the heterogeneous nature of the disorder. APOE*4 is the strongest genetic risk factor for AD. Genome-wide association studies have identified more than 30 additional loci, each having relatively small effect size. Known AD loci explain only about 30% of the genetic variance, and...

Background We examined how the relationship between education and latelife cognitive impairment (defined as a Mini Mental State Examination score below 24) is influenced by age, sex, ethnicity, and Apolipoprotein E epsilon 4 (APOE*4). Methods Participants were 30,785 dementia-free individuals aged 55-103 years, from 18 longitudinal cohort studies,...

Subjective cognitive decline (SCD) is recognized as a risk stage for Alzheimer`s disease (AD) and other dementias, but its prevalence is not well known. We aimed to use uniform criteria to better estimate SCD prevalence across international cohorts. Therefore, we combined individual participant data for 16 cohorts from 15 countries (members of the...

Background: Excessive daytime sleepiness is associated with chronic disorders of aging and mortality. Because longitudinal data are limited on the development of sleep disturbances and cognitive changes in older adults, we investigated the demographic, clinical, and cognitive predictors of self-reported daytime sleepiness over ten years. Methods:...

Background Longitudinal studies predictably experience non-random attrition over time. Among older adults, risk factors for attrition may be similar to risk factors for outcomes such as cognitive decline and dementia, potentially biasing study results. Objective To characterize participants lost to follow-up which can be useful in the study design...