Graciela Muniz

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

Brain Age Gap has been associated with dementia in old age. Less is known relating brain age gap to dementia risk-factors or cognitive performance in middle-age. Cognitively healthy, middle-aged subjects from PREVENT-Dementia had comprehensive neuropsychological, neuroimaging and genetic assessments. Brain Ages were predicted from T1-weighted 3T MR...

Background Females have a higher age-adjusted incidence of Alzheimer’s Disease (AD) than males, even when accounting for longer lifespan and, therefore, stand to benefit the most from dementia prevention efforts. As exposure to many modifiable risk factors for dementia begins in mid-life, interventions must be implemented from middle-age. Building...

Job satisfaction has been found to increase with age. However, we still have a very limited understanding of how job satisfaction changes as people approach retirement. This is important as the years before retirement present specific challenges for older workers. We employed a time-to-retirement approach to investigate (i) mean levels of change in...

Background The Mini-Mental State Examination (MMSE) and the Montreal Cognitive Assessment (MoCA) questionnaires are commonly used to measure global cognition in clinical trials. Because these scales are discrete and bounded with ceiling and floor effects and highly skewed, their analysis as continuous outcomes presents challenges. Normality assumpt...

The apolipoprotein (APOE) e4 allele is associated with brain changes in healthy carriers that are similar to changes observed in patients with Alzheimers Disease, including abnormalities in functional connectivity. The trajectory of these changes across the lifespan, specifically in early adulthood is still not clear. This study explores the link b...

Delirium is associated with the risk of future long-term cognitive impairment, but the degree to which markers of neuronal injury may be distinct or shared with dementia has yet to be comprehensively described. We investigated CSF biomarkers of dementia, astrocytosis and neuronal damage in a clinical cohort with persistent delirium, comparing them...

Background and Objectives Cross sectional studies have shown improvements in cognition in later born cohorts. However, it remains unclear whether these cohort effects extend beyond cognitive levels and are also detectable in the rate of age-related cognitive decline. Additionally, evidence is scarce on the presence and consistency of cohort effects...

Objective: To explore associations between measurements of the ocular microvasculature in the choroid (a highly vascularised layer posterior to the retina) and genetic Alzheimer's disease risk. Methods: We measured the choroidal vasculature appearing in optical coherence tomography scans of 69 healthy, mid-life individuals in the PREVENT cohort. Th...

INTRODUCTION We tested associations between two retinal measures (optic disc pallor, peripapillary retinal nerve fiber layer [pRNFL] thickness) and four magnetic resonance imaging markers of cerebral small vessel disease (SVD; lacunes, microbleeds, white matter hyperintensities, and enlarged perivascular spaces [ePVSs]). METHODS We used PallorMetr...

The use of anticholinergic drugs has been associated with adverse health outcomes. However, their effects cannot be completely separated from the effects of general polypharmacy using standard methods. The objective of this study was to explore the extent to which the detrimental health effects attributed to anticholinergic burden measured by antic...

Chronic exposure to stressor factors has been proposed as a cause of structural changes in the brain in the context of dementia. One of these changes can be characterised by the fibre integrity loss, susceptible to be measured by diffusion tensor imaging (DTI). In this study, we obtained DTI whole brain metrics to relate them with allostatic load (...

Allostatic load (AL) is a cause of structural brain changes related to dementia. White matter hyperintensities (WMH) are brain MRI abnormalities associated with small vessel disease, neurodegenerative and neuroinflammatory conditions. Here, we studied differences in tract-specific WMH volume across three risk levels of AL in freedementia Chilean su...

To contribute to our understanding of cohort differences and the Flynn effect in the cognitive decline among older Americans, this study aims to compare rates of cognitive decline between two birth cohorts within a study of older Americans and to examine the importance of medical and demographic confounders. Analyses used data from the National Hea...

Importance Traumatic brain injuries (TBI) represent an important, potentially modifiable risk factor for dementia. Despite frequently observed vascular imaging changes in individuals with TBI, the relationships between TBI-associated changes in brain imaging and clinical outcomes have largely been overlooked in community cases of TBI. Objective To...

Brain atrophy and cortical thinning are typically observed in people with Alzheimer's disease (AD) and, to a lesser extent, in those with mild cognitive impairment. In asymptomatic middle‐aged apolipoprotein ε4 (ΑPOE4) carriers, who are at higher risk of future AD, study reports are discordant with limited evidence of brain structural differences b...

The prevalence of informal caregiving is increasing as populations across the world age. Caregiving has been found to be associated with poor mental health outcomes including depressive symptoms. The purpose of this study is to examine the mean trajectory of depressive symptomatology in older caregivers in a large European sample over an eight-year...

Background Only few studies of Allostatic Load (AL) have been conducted in Latin/Hispanic populations, and even fewer performed in South American cohorts. Here, we replicated a recently proposed algorithm to derive an AL index in a Chilean cohort of cognitive healthy adults. Methods Using data from the GERO cohort (n = 166, age 76.92 ± 5.07 years,...

Studies examining lifestyle and cognitive decline often use healthy lifestyle indices, making it difficult to understand implications for interventions. We examined associations of 16 lifestyles with cognitive decline. Data from 32,033 cognitively-healthy adults aged 50-104 years participating in prospective cohort studies of aging from 14 European...

Introduction White matter hyperintensities (WMH) in Alzheimer’s disease (AD) have traditionally been associated with cerebrovascular diseases. Amyloid β (Aβ) deposition reportedly contributes to WMHs; however, this relationship remains unclear in dementia-free subjects with cognitive complaints (CC). Here, we explored the relationship between WMHs...

Incorporating person-centered outcomes into clinical trials for neurodegenerative diseases has been challenging due to a deficiency in quantitative measures. Meanwhile, the integration of personally meaningful treatment targets in clinical practice remains qualitative, failing to truly inform evaluations, therapeutic interventions and longitudinal...

PREVENT is a multi-centre prospective cohort study in the UK and Ireland that aims to examine midlife risk factors for dementia and 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 neurodegen...

Background and purpose The Mediterranean diet (MedDiet) has been associated with reduced dementia incidence in several studies. It is important to understand if diet is associated with brain health in midlife, when Alzheimer's disease and related dementias are known to begin. Methods This study used data from the PREVENT dementia programme. Three...

Background Visit-to-visit variability in single biological measurements has been associated with cognitive decline and an elevated risk of cardiovascular diseases (CVD). However, the effect of visit-to-visit variability in multiple biological measures is underexplored. We investigated the effect of visit-to-visit variability in blood pressure (BP),...

Purpose We sough to develop an automatic method of quantifying optic disc pallor in fundus photographs and determine associations with peripapillary retinal nerve fiber layer (pRNFL) thickness. Methods We used deep learning to segment the optic disc, fovea, and vessels in fundus photographs, and measured pallor. We assessed the relationship betwee...

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: Availability of large longitudinal population health and aging studies, such as the English Longitudinal Study on Ageing, hold many opportunities for the examination of the development of Frailty over time. Lacking are psychometrically robust longitudinal measurement of the concepts of frailty required for accurate and reliable estimate...

This essay highlights the interplay between the neighbourhood structural environment and neighbourhood perceptions on dementia by articulating how an individual’s perception of neighbourhood, with respect to their individual differences, may provide key insights to understand the link between the neighbourhood and dementia.

INTRODUCTION Hypertension and diabetes are modifiable risk factors for dementia. We aimed to assess rural‐urban disparities in the diagnosis and treatment of these conditions among aging Indians. METHODS Participants (n = 6316) were from two parallel, prospective aging cohorts in rural and urban India. Using self‐report and clinical/biochemical as...

A satisfying job is important for workers across their work lifespan. However, before workers retire, it is often assumed that they start to become less attached to their workplace and focus on other life areas instead. This supposed disengagement process, however, is not well understood. To date, few studies have examined whether the importance th...

Background: Most previous studies of frailty trajectories in older adults focus on the average trajectory and ignore death. Longitudinal quantile analysis of frailty trajectories permits the definition of reference curves, and the application of mortal cohort inference provides more realistic estimates than models that ignore death. Methods: Usi...

Introduction There is emerging evidence that speech may be a potential indicator and manifestation of early Alzheimer’s disease (AD) pathology. Therefore, the University of Edinburgh and Sony Research have partnered to create the Speech for Intelligent cognition change tracking and DEtection of Alzheimer’s Disease (SIDE-AD) study, which aims to dev...

Background: The global phenomenon of increasing older adult populations is evident across diverse societies, including historically youthful middle- and low-income countries. Conducting population-specific research in low- and middle-income countries becomes imperative to gather pertinent evidence for crafting interventions tailored to the unique n...

The apolipoprotein E ɛ4 allele is the primary genetic risk factor for the sporadic type of Alzheimer’s disease. However, the mechanisms by which apolipoprotein E ɛ4 are associated with neurodegeneration are still poorly understood. We applied the Neurite Orientation Dispersion Model to characterize the effects of apolipoprotein ɛ4 and its interacti...

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...

Multimorbidity—the co-existence of at least two chronic health conditions within the same individual—is an important global health challenge. In high-income countries (HICs), multimorbidity is dominated by non-communicable diseases (NCDs); whereas the situation may be different in low- and middle-income countries (LMICs), where chronic communicable...

Background Unmet health needs have the potential to capture health inequality. Nevertheless, the course of healthcare needs fulfilment, and the role of multimorbidity in this process remains unclear. This study assessed the bidirectional transitions between met and unmet health needs and the transition to death and examined the effect of multimorbi...

Background Life course epidemiology examines associations between repeated measures of risk and health outcomes across different phases of life. Empirical research, however, is often based on discrete-time models that assume that sporadic measurement occasions fully capture underlying long-term continuous processes of risk. Methods We propose (i)...

To date, there is a considerable heterogeneity of methods to score Allostatic Load (AL). Here we propose a comprehensive algorithm (ALCS) that integrates commonly used approaches to generate AL risk categories and assess associations to brain structure deterioration. In a cohort of cognitively normal mid-life adults (n = 620, age 51.3 ± 5.48 years)...

Background It is essential both drug and lifestyle‐based interventions aimed to delay the onset of advanced cognitive decline deliver a meaningful outcome for the patient. In the early stages of Alzheimer’s disease and related dementias (ADRDs), patient‐reported outcome (PRO) measures should be used in parallel with biological investigations of ADR...

Background Brain Age Gap (BAG) represents the difference between an individual’s predicted age, derived from machine learning models trained on neuroimaging data, and their chronological age. BAG has been associated with dementia and cognition in old age. Less is known relating BAG to dementia risk‐factors or cognitive performance in middle‐age. M...

Background The APOE ε4 allele is the primary genetic risk factor for the sporadic type of Alzheimer’s disease (AD). However, the mechanisms by which APOE ε4 is associated with neurodegeneration are still poorly understood. Here, we applied the NODDI to characterise the effects of APOE ε4 and its interactions with age and education on cortical micro...

Background The Mediterranean diet (MedDiet) has been associated with better cardiometabolic and brain health. Research has suggested differences in these associations between men and women, with men typically reported to benefit more from higher MedDiet adherence. However there remains a lack of research in this area in non‐Mediterranean countries....

Background Cerebral microbleeds (CMB) are predictive of increased risk of dementia and stroke. Although commonly regarded as vascular markers, CMB can also stem from non‐vascular aetiologies like head injuries or traumatic brain injury (TBI), although these are often overlooked. Therefore, this study examines CMB in relation to TBI, and their diffe...

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. Intellectually, physically, and socially stimulating lifestyle activities are associated with maintenance of l...

Background Depressive symptoms vary over the life course and may result from a multitude of causes. With consolidating evidence about depressive symptoms as risk factor of dementia, and previous findings suggesting shared biological pathways of depression and dementia, involving e.g., inflammation, it remains unclear if depressive symptoms reflect...

Background There is emerging evidence that speech could be a potential indicator and manifestation of early Alzheimer’s disease (AD) pathology. Symptomatic AD may change an individual’s language, especially certain elements in speech such as elaboration and attribution. Therefore, the University of Edinburgh and Sony Group Corporation are collabora...

Background Carriership of the apolipoprotein ε4 (APOE4) allele confers a heightened risk for the development of Alzheimer’s disease (AD). Cerebral blood flow (CBF) is decreased in prodromal and established AD, however findings in the preclinical stage are mixed, with some studies reporting increases. CBF can be impacted by many factors including th...

Background It is well acknowledged that Alzheimer’s Disease (AD) neuropathology start decades before clinical manifestations, but the brain mechanism of sporadic AD in midlife remains unclear. Resting‐state functional connectivity (FC) is increasingly used to understand early brain changes in Alzheimer’s disease (AD) (Sperling, 2011; van den Heuvel...

Background It is now acknowledged that Alzheimer’s Disease (AD) processes are present decades before the symptoms manifest, 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 lif...

Background Cerebral microbleeds (CMB) are predictive of increased risk of dementia and stroke. Although commonly regarded as vascular markers, CMB can also stem from non‐vascular aetiologies like head injuries or traumatic brain injury (TBI), although these are often overlooked. Therefore, this study examines CMB in relation to TBI, and their diffe...

Background Carriership of the apolipoprotein ε4 (APOE4) allele confers a heightened risk for the development of Alzheimer’s disease (AD). Cerebral blood flow (CBF) is decreased in prodromal and established AD, however findings in the preclinical stage are mixed, with some studies reporting increases. CBF can be impacted by many factors including th...

Background The APOE e4 allele is the primary genetic risk factor for the sporadic type of Alzheimer’s disease (AD). However, the mechanisms by which APOE e4 is associated with neurodegeneration are still poorly understood. Here, we applied the NODDI to characterise the effects of APOE e4 and its interactions with age and education on cortical micro...

Multimorbidity is a risk factor for patient-important outcomes including quality of life and functional decline. Multimorbidity research has focused mainly on disease counts, with less attention to patterns among chronic conditions. Network analysis has been increasingly used to examine multimorbidity clusters, but there are no guidelines for its c...

Background Motoric cognitive risk syndrome (MCR) - objective slow gait and subjective cognitive complaints - is quick and easy to measure, making it a potentially useful clinical tool for identifying those at high risk of developing dementia. This is the first exploration of MCR syndrome’s predictive ability for incident dementia in a Scottish coho...

Introduced three decades ago, the concept of Allostatic Load (AL) describes the wear and tear of the physiological response to chronic stress, and how sustained demand overloads the systems involved, deplete their resources, and leads them to fail. Current evidence shows positive relationship between AL and risk of developing conditions such as dep...

Frailty prevalence estimates vary considerably (4.0% to 59.1% in one review). Understanding these differences and what drives frailty among individuals could lead to more focused interventions. Breaking frailty into subdomains and exploring their relationships is one approach to this. A 127-item overall Frailty Index (FI) based on data collected on...

Evidence on the U.S. hospital infrastructure to address dementia is scant, obscuring health improvement efforts. This study investigates the availability of Alzheimer’s Centers (ACs) in U.S. hospitals. Data come from the: (1) 2010 – 2021 American Hospital Association Annual Survey; (2) 2020 Area Health Resource File; and (3) 2020 U.S. Census. Utili...

Frailty and dementia affect many older adults worldwide. As the world’s population ages, the number of people experiencing frailty and dementia is increasing, posing significant challenges for individuals, health care systems and caregivers. Here, we aim to assess the link between the evolution of frailty and the time to dementia diagnosis in the o...

Longitudinal research on cognitive change has mostly been focused on mean change in cognition and its associated factors. In this paper, we aim to assess the role of socio-demographic characteristics on different percentiles of the distribution of cognitive trajectories considering sample attrition due to death and intermittent missing data. We use...

Promoting healthy ageing requires an in-depth understanding of health inequalities. There are many different ways in which experiences of health and care may be inequitable, and numerous ways of studying this. In this symposium, we present findings from five disparate studies, united by an intention to shed light on unequal ageing. Our work utilise...

The existing literature consistently finds that personality traits are associated with dementia and with risk of mortality. However, few studies have simultaneously examined the impact of traits on dementia while accounting for death as a competing risk, which is critical as dementia and mortality are dependent outcomes and the likelihood of each i...

Dementia risk has been established to be partly attributable to modifiable social and behavioral risk factors. However, the biological pathways behind these associations and the effects of intervening on present risk factors to reduce dementia risk have not been fully elucidated. The symposium will present latest research on the social determinants...

Background: Understanding geographical variation of dementia could highlight important modifiable socio-environmental risk factors. A previous systematic review (2012) identified an increased risk of Alzheimer dementia in in rural living in High-Income Countries (HICs), with a dearth of studies in Low to Middle-Income Countries (L-MICs). We updated...

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...