Graciela Muniz

Medical Research Council (UKRI) | mrc · MRC Biostatistics Unit

Objectives To quantify inconsistent self-reporting of chronic conditions between the baseline (2011–2015) and first follow-up surveys (2015–2018) in the Canadian Longitudinal Study on Aging (CLSA), and to explore methods to resolve inconsistent responses and impact on multimorbidity. Methods Community-dwelling adults aged 45–85 years in the baseli...

Introduction As the global population ages, the economic, societal, and personal burdens associated with worsening cognition and dementia onset are growing. It is therefore becoming ever more critical to understand the factors associated with cognitive decline. One such factor is sleep. Adequate sleep has been shown to maintain cognitive function a...

Introduction Women are significantly more likely to develop Alzheimer's disease and related dementias (ADRD) than men. Suggestions to explain the sex differences in dementia incidence have included the influence of sex hormones with little attention paid to date as to the effect of hormonal contraception on brain health. The aim of this scoping rev...

Background and Objectives The existing literature highlights the importance of reading books in middle-to-older adulthood for cognitive functioning; very few studies, however, have examined the importance of childhood cognitive resources for cognitive outcomes later in life. Research Design and Methods Using data from 11 countries included in the...

An active lifestyle has been associated with better cognitive performance in many studies. However, most studies have focused on leisure activities or paid work, with less consideration of the kind of prosocial activities, many people engage in, including volunteering, grandparenting, and family care. In the present study, based on four waves of th...

Women are significantly more likely to develop Alzheimer’s disease and related dementias (ADRD) than men. Suggestions to explain the sex differences in dementia incidence have included the influence of sex hormones with little attention paid to date as to the effect of hormonal contraception on brain health. The aim of this scoping review is to eva...

Alzheimer’s Disease (AD) presents a formidable global health challenge, with a predicted rise in affected individuals in the coming years. Consequently, the development of methods for early detection and monitoring methods are crucially important. Recent studies have highlighted the potential of retinal microvasculature changes captured through opt...

To date, there is a lack of universally agreed values to calculate an Allostatic Load (AL) index and a considerable heterogeneity of methods. In this study we propose a comprehensive algorithm that integrates several approaches and generate risk categories to assess associations between AL and brain structure deterioration. In a cohort of cognitive...

Background: Evidence suggests that risk factors for Alzheimer’s disease and related dementias (ADRD) are at least partially modifiable, and that lifestyle risk accumulates as we age. However, the prevalence and impact of lifestyle-related risk factors in young adulthood (i.e., 18-39 years) remain poorly understood, with some risk factors that are d...

Objectives To investigate the availability of Alzheimer’s Centers (ACs) in US hospitals. Methods Utilizing the American Hospital Association Annual Survey, Area Health Resource File, and US Census ( n = 3251), we employed multivariable logistic regression to examine hospital, county, and regional predictors of AC availability. Results Large hospi...

Background: Evidence suggests that risk factors for Alzheimer’s disease and related dementias (ADRD) are at least partially modifiable, and that lifestyle risk accumulates as we age. However, the prevalence and impact of lifestyle-related risk factors in young adulthood (i.e., 18-39 years) remain poorly understood, with some risk factors that are d...

Background While prolonged labour market participation becomes increasingly important in ageing societies, evidence on the impacts of entering or exiting work beyond age 65 on cognitive functioning is scarce. Methods We use data from two large population-representative data sets from South Korea and the USA to investigate and compare the effects o...

Life course epidemiology seeks to understand the intricate relationships between risk factors and health outcomes across different stages of life to inform prevention and intervention strategies to optimize health throughout the lifespan. However, extant evidence has predominantly been based on separate analyses of data from individual birth cohort...

PREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine mid-life risk factors for dementia , identify and describe the earliest indices of disease development. The PREVENT dementia programme is one of the original epidemiological initiatives targeting midlife as a critical window for intervention in neurodegene...

It is now acknowledged that Alzheimer′s disease (AD) neuropathology starts decades before the onset of clinical symptoms, but it remains unknown whether modifiable lifestyle factors can protect against these incipient AD processes, early, in mid-life. Cognitive reserve can explain cognitive preservation in some older adults despite ageing or dement...

Background: Better understanding of worldwide variation in simple tests of cognition and global function in older adults would aid the delivery and interpretation of multi-national studies of the prevention of dementia and functional decline. Method: In six RCTs that measured cognition with the mini-mental state examination (MMSE), Montreal cogn...

The Mediterranean diet (MedDiet) has been associated with better brain health and reduced incidence of dementia. Few studies have compared the effects of the MedDiet in early Alzheimer's disease or compared the effects of the diet within and outside of the Mediterranean region. The Mediterranean diet adherence screener (MEDAS) and MEDAS continuous...

Background and aims: The Mediterranean diet (MedDiet) has been associated with better cardiovascular health in a number of studies. This study aimed to explore cross-sectional associations between MedDiet adherence in the PREVENT Dementia (PREVENT) programme, stratified by sex. Methods and results: Three MedDiet scores were calculated (MEDAS, ME...

Background Past evidence shows that changes in functional brain connectivity in multiple resting-state networks occur in cognitively healthy individuals who have non-modifiable risk factors for Alzheimer’s Disease. Here, we aimed to investigate how those changes differ in early adulthood and how they might relate to cognition. Methods We investiga...

Objective: Using a large longitudinal sample of adults from the Midlife in the United States (MIDUS) study, the present study extended a recently developed hierarchical model to determine how best to longitudinally model cumulative stress, and to determine whether the rate of change in stress or the level of cumulative stress over time are stronger...

Objective This paper models cognitive aging, across mid and late life, and estimates birth cohort and sex differences in both initial-levels and aging trajectories over time in a sample with multiple cohorts and a wide span of ages. Methods The data used in this study came from the first nine waves of the English Longitudinal Study of Ageing (ELSA...

Background 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...

Background Polypharmacy, the concurrent use of multiple medicines, is increasing. Population‐wide studies of its association with dementia are lacking. We examined this relationship longitudinally, at a national level. Method We used National Health Service community prescribing data from all adults in Scotland aged ≥50 years who received at least...

Background The COVID‐19 pandemic has impacted daily life worldwide, with possible negative consequences for cognitive health. Self‐reported cognitive symptoms are linked to the development of Alzheimer’s disease and related dementias (ADRDs). Identifying risk and protective factors for cognitive symptoms during the pandemic is an important step tow...

The potential for future prevention of Alzheimer’s disease and related dementias (ADRD) through healthy lifestyle change is spurring a positive brain health movement. However, most ADRD research continues to focus on mid- and later life. We lack evidence regarding risk exposure and protective factors in young adulthood, i.e., 18–39 years. Brain cap...

Objectives: Assessing for recovery in delirium is essential in guiding ongoing investigation and treatment. Yet, there is little scrutiny and no research or clinical consensus on how recovery should be measured. We reviewed studies which used tests of neuropsychological domains and functional ability to track recovery of delirium longitudinally in...

Background Alzheimer’s disease (AD), type 2 diabetes mellitus (characterised by insulin resistance) and depression are significant challenges facing public health. Research has demonstrated common comorbidities among these three conditions, typically focusing on two of them at a time. Objective The goal of this study, however, was to assess the in...

Introduction As the global population ages, the economic, societal, and personal burdens associated with worsening cognition and dementia onset are growing. It is therefore becoming ever more critical to understand the factors associated with cognitive decline. One such factor is sleep. Adequate sleep has been shown to maintain cognitive function a...

Background The Eatwell guide reflects the UK government’s recommendations for a healthy and balanced diet. Previous research has identified associations between healthy eating patterns and both cardiovascular and brain health, although there is little evidence specifically focusing on the Eatwell Guide. To date no research has investigated associat...

Background: It is currently unclear whether (and when) physical function exhibits a terminal decline phase, i.e. a substantial acceleration of decline in the very last years before death. Methods: 702 deceased adults aged 70 years and older from the Yale PEP Study provided 4,133 measurements of physical function (Short Physical Performance Batte...

Cerebral hemodynamic alterations have been observed in apolipoprotein ε4 (APOE4) carriers at midlife, however the physiological underpinnings of this observation are poorly understood. Our goal was to investigate cerebral blood flow (CBF) and its spatial coefficient of variation (CoV) in relation to APOE4 and a measure of erythrocyte anisocytosis (...

Background: There is still a need for more information about the different trajectories of responsive behaviours that people living with dementia present in long-term care homes (LTC). Objective: This study identified subgroups of individuals with similar trajectories of responsive behaviours related to dementia in LTC and evaluated the role of...

It is well acknowledged that the pathological processes of Alzheimer′s disease (AD) start decades before clinical manifestations, but early indicators of AD in midlife remain unclear. Functional segregation of brain networks has recently emerged as a key indicator of brain health. In this study, we investigated the vulnerability of intrinsic brain...

Women carry a higher burden of Alzheimer’s disease (AD) compared to men, which is not accounted entirely by differences in lifespan. To identify the mechanisms underlying this effect, we investigated sex-specific differences in the progression of familial AD in humans and in APPswe/PS1ΔE9 mice. Activity dependent protein translation and associative...

Growing evidence supports the use of plasma levels of tau phosphorylated at threonine 181 (p-tau181), amyloid-β, neurofilament light (NfL), and glial fibrillary acidic protein (GFAP) as promising biomarkers for Alzheimer’s disease. While these blood biomarkers are promising for distinguishing people with Alzheimer’s disease from healthy controls, t...

The Flynn effect refers to increases over time in measured (particularly fluid) intelligence of approximately 3 IQ points per decade. We define the Flynn effect at the family level, using longitudinal data and two new family-level cohort definitions. Multilevel growth curve analyses of the National Longitudinal Survey of Youth 1979 data showed that...

Further understanding of the associations between personality traits and allostatic load (AL) may be important for predicting, addressing, and optimizing health outcomes. This review synthesized the existing literature reporting the association between the Big Five personality traits and AL in adults to identify the generalizability and robustness...

Although delirium is a significant clinical and public health problem, little is understood about how specific vulnerabilities underlie the severity of its presentation. Our objective was to quantify the relationship between baseline cognition and subsequent delirium severity. We prospectively investigated a population-representative sample of 1510...

Background Alzheimer’s disease, type 2 diabetes mellitus, and depression are significant challenges facing public health. Research has demonstrated common comorbidities amongst these three conditions, typically focusing on two of them at a time. Objectives The goal of this study, however, was to assess the interrelationships between the three cond...

Background: Motoric Cognitive Risk (MCR) is a syndrome characterised by measured slow gait speed and self-reported cognitive complaints. MCR is a high-risk state for adverse health outcomes in older adults, particularly cognitive impairment and dementia. Previous studies have identified risk factors for MCR, but the effect of socioeconomic status...

Background: Anticholinergic drugs block muscarinic receptors in the body. They are commonly prescribed for a variety of indications and their use has previously been associated with dementia and cognitive decline. Methods: In UK Biobank participants with linked health-care records (n=163,043, aged 40-71 at baseline), of whom about 17,000 had MRI...

Background: Age-related changes in frailty have been documented in the literature. However, the evidence regarding changes in frailty prior to death is scarce. Understanding patterns of frailty progression as individuals approach death could inform care and potentially lead to interventions to improve individual's well-being at the end of life. In...

An active lifestyle has been associated with better cognitive performance in many studies. However, most studies have focused on leisure activities or paid work, with less consideration of the kind of prosocial activities many people engage in, including volunteering, grandparenting and family care. In the present study, based on four waves of the...

It is now acknowledged that Alzheimer's Disease (AD) processes are present decades before the onset of clinical symptoms, but whether lifestyle activities can protect against these early AD processes in mid-life remains poorly understood. Furthermore, the impact of sex as a biological variable on associations between dementia risk, protective lifes...

Background: A crucial part of delirium care is determining if the delirium episode has resolved. Yet, there is no clear evidence or consensus on which assessments clinicians should use to assess for delirium recovery. Objective: To evaluate current opinions from delirium specialists on assessment of delirium recovery. Design: Online questionnaire-b...

Objectives: To assess the prevalence and factors associated with multimorbidity in a community-dwelling general adult population on a large Health and Demographic Surveillance System (HDSS) scale. Design: Population-based cross-sectional study. Setting: South East Asia Community Observatory HDSS site in Malaysia. Participants: Of 45 246 particip...

Adherence to the Mediterranean diet (MedDiet) has been associated with better cognitive performance, lower incidence of dementia, stroke and lower Alzheimer’s disease (AD) biomarker burden (Scarmeas et al, 2018). Improving dietary patterns in at‐risk populations may improve brain health, reducing incidence of dementia and stroke (Lewis et al, 2014;...

Research suggests that physical activity (PA) protects against cognitive impairment in older adulthood; however, the extent to which PA engagement throughout older adulthood influences the simultaneous risk of transitioning to cognitively impaired states and death is unclear. Applying coordinated data analysis across 14 studies, multi-state surviva...

The Mediterranean diet (MedDiet) is a primarily plant‐based eating pattern. High adherence to a MedDiet has been associated with a 10‐40% lower incidence of dementia. There is limited evidence exploring associations between the MedDiet and Alzheimer’s disease (AD) pathology. Our study explored cross‐sectional associations between MedDiet and AD out...

To contribute to our understanding of cohort differences and the Flynn Effect in cognitive declines, this study aims to: 1) describe and compare cognitive decline trends of two nationally representative American older cohorts; 2) investigate significant determinants of cognitive declines and the cohort differences. The analysis used data from the N...

The Flynn effect (Flynn, 1984; 1987) refers to increases in cognitive performance, for later-born cohorts. It has been documented globally, occurring for more than a century. In a meta-analysis, Pietschnig and Voracek (2015) noted that the effect may be even stronger in adults than in children, though little research has addressed this topic (or it...

Frailty has become an increasingly important aspect in the field of health research in studies of vulnerability to adverse events and individuals functioning due to accumulated health deficits. Yet, there is no agreement on how to measure frailty or identify adults as frail, resulting in high heterogeneity between estimates of frailty and identific...

Alzheimer’s Disease, the leading cause of dementia, is over‐represented in females. The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late‐onset AD and is associated with aberrant cerebrospinal fluid levels (CSF) of total tau (t‐tau), phosphorylated tau (p‐tau), and amyloid‐β (Aβ). There is some evidence that sex may me...

Declines in cognitive functioning with increased age, on average and individually, is well documented and demonstrated to be related to genetics and a variety of life course risk factors, many of which are modifiable. Related to population cognitive aging is the phenomenon of the Flynn effect, the finding of increasing cognitive test scores across...

The research construct of frailty in aging requires a measure with sound psychometric properties, that is stable across longitudinal points of observation. Using Exploratory Factor Analysis and Longitudinal Mixed Methods, we developed a five-factor research measures of frailty that is robust across time. Standardized regression scores for each fact...

Scarce evidence exists about frailty trajectories, but the evidence suggests that women live longer with higher levels of frailty. When progression of frailty was studied, the focus has been on mean trajectories and research has ignored death. Here, we aim to assess the role of sex, age, and education in different quantiles of the distribution of f...

Motoric Cognitive Risk (MCR) syndrome combines slow walking and self-reported cognitive complaints. It is a quick and simple way of identifying individuals at high risk of developing dementia. MCR has not been described in a Scottish population to date. This study describes the prevalence and associated factors of MCR in a community-dwelling sample...

Cross sectional studies have shown cohort effects in cognition, limited research exists about cohort effects on cognitive trajectories. Indeed, most longitudinal research conducted to study aging-related cognitive change focus on the association between risk factors and mean change in cognition, considering individual differences too, but longitudi...

Introduction: Neuropsychological assessments are inexpensive and efficient methods to understand the cognitive abilities of individuals in research studies and clinical settings. Normative scores for such measures are crucial in serving as a reference standard for identifying cognitively healthy and impaired individuals belonging to similar sociod...

Background: Adherence to the Mediterranean diet (MedDiet), a primarily plant-based eating pattern, has been associated with lower dementia incidence. Much of the research has focused on Alzheimer’s disease (AD) dementia and mild cognitive impairment (MCI), with less research looking at the preclinical symptomatically silent stages that pre-empt MCI...

Background: It is now acknowledged that Alzheimer's disease (AD) processes are present decades before the onset of clinical symptoms, but it remains unknown whether lifestyle factors can protect against these early AD processes in mid-life. Objective: We asked whether modifiable lifestyle activities impact cognition in middle-aged individuals wh...

Previous studies have demonstrated an association between adherence to the Mediterranean diet (MedDiet) and better cognitive performance, lower incidence of dementia and lower Alzheimer's disease biomarker burden. The aim of this systematic review was to evaluate the evidence base for MedDiet associations with hippocampal volume and white matter hy...

The entorhinal cortex (EC) is the first cortical brain region to exhibit neurodegeneration in Alzheimer’s disease (AD). Given that the EC contains unique grid cells underpinning path integration, tests probing this aspect of navigation may have added value in detecting AD in its earliest preclinical stages. Building on our past work showing that a...

Machine learning (ML) methodology used in the social and health sciences needs to fit the intended research purposes of description, prediction, or causal inference. This paper provides a comprehensive, systematic meta-mapping of research questions in the social and health sciences to appropriate ML approaches by incorporating the necessary require...

Background Considerable overlap exists between the risk factors of dementia and cerebral small vessel disease (SVD). However, studies remain limited to older cohorts wherein pathologies of both dementia (e.g. amyloid) and SVD (e.g. white matter hyperintensities) already co-exist. In younger asymptomatic adults, we investigated differential associat...

Objectives: Motoric Cognitive Risk (MCR) is a gait-based predementia syndrome that is easy to measure and prognostic of dementia and falls. We aimed to examine the prevalence and risk factors for MCR, and assess its overlap with Mild Cognitive Impairment, Prefrailty, and Frailty, in a cohort of older Scottish adults without dementia. Methods: In...

Background and objective More research is required to understand associations of body mass index (BMI) and sarcopenia with cognition, especially in Latin America. The objective of this study was to investigate associations of BMI and sarcopenia with mild cognitive impairment in Colombia. Design, setting, and participants Data were from the Nationa...

Cerebrovascular changes associated with Alzheimer’s disease (AD) can occur years before the onset of symptoms. Studies have suggested that changes in the retina may act as a surrogate for cerebrovascular changes in the brain, hence the retina might be a source of biomarkers for declining vascular brain health. Optical Coherence Tomography Angiograp...

Background Anticholinergic drugs block muscarinic receptors in the body. They are commonly prescribed for a variety of indications and their use has previously been associated with dementia and cognitive decline. Methods UK Biobank participants with linked health-care records (n=163,043, aged 40-71 at baseline), for about 17,000 of which MRI data...

It is well acknowledged that Alzheimer′s Disease (AD) pathological processes start decades before clinical manifestations, but the brain mechanism of sporadic AD in midlife remains unclear. To address this gap, we examined whether risk factors for late-life AD are associated with disrupted connectivity between two key structures in AD pathophysiolo...

Background Alzheimer's Disease, the leading cause of dementia, is over-represented in females. The apolipoprotein E (APOE) ε4 allele is the strongest genetic risk factor for late-onset AD and is associated with aberrant cerebrospinal fluid levels (CSF) of total tau (t-tau), phosphorylated tau (p-tau), and amyloid-β (Aβ). There is some evidence that...

Type 2 diabetes is a robust predictor of cognitive impairment. Impairment in allocentric processing may help identify those at increased risk for Alzheimer’s disease dementia. The objective of this study was to investigate the performance of participants with and without diabetes on a task of allocentric spatial processing. This was a cross‐section...

Background Anticholinergic drugs block muscarinic receptors in the body. They are commonly prescribed for a variety of indications and their use has previously been associated with dementia and cognitive decline. Methods In UK Biobank participants with linked health-care records (n=171,266, aged 40-71 at baseline), we calculated total anticholinerg...

Characterising associations between the methylome, proteome and phenome may provide insight into biological pathways governing brain health. Here, we report an integrated DNA methylation and phenotypic study of the circulating proteome in relation to brain health. Methylome-wide association studies of 4058 plasma proteins are performed (N = 774), i...

Background Macrostructural brain alterations in the form of brain atrophy or cortical thinning typically occur during the prodromal Alzheimer’s disease stage. Mixed findings largely dependent on the age of the examined cohorts have been reported during the preclinical, asymptomatic disease stage. In the present study, our aim was to examine the ass...

Neighborhood features have been postulated to be key predictors of frailty. However, evidence is mainly limited to cross-sectional studies without indication of long-term impact. We explored how neighborhood social deprivation (NSD) across the life course is associated with frailty and frailty progression among older Scottish adults. Participants (...

Background Older adults living in the community may have daily needs for help to perform different types of activities. In developing countries, older adults face the additional challenge of lacking sufficient economic means to face their increasing needs with ageing, and health and social policies may be under pressure. The aim of this study was t...