Matthew Pase

Monash University (Australia) · Turner Institute for Brain and Mental Health

Background Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort. Methods The sleep regularity index (SRI...

Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort. The sleep regularity index (SRI) was calculated as...

Importance Slow-wave sleep (SWS) supports the aging brain in many ways, including facilitating the glymphatic clearance of proteins that aggregate in Alzheimer disease. However, the role of SWS in the development of dementia remains equivocal. Objective To determine whether SWS loss with aging is associated with the risk of incident dementia and e...

Background: Magnetic resonance imaging (MRI) visible perivascular spaces (PVS) are associated with the risk of incident dementia but their association with the early stages of cognitive impairment remains equivocal. Objective: We examined the association between MRI visible PVS and the risk of incident mild cognitive impairment (MCI) in the comm...

Objectives Psychological stress has been proposed as a risk factor for cognitive impairment and dementia. However, it remains unclear how an individual’s stress-coping ability (i.e., psychological resilience) is related to cognition. This cross-sectional study investigated whether perceived stress and psychological resilience were associated with c...

Psychological stress is associated with dementia risk. However, the underlying mechanisms are unclear. This cross-sectional study examined the association between self-reported psychological stress and cerebrospinal fluid (CSF) biomarkers of Alzheimer’s disease and neurodegeneration in 73 cognitively unimpaired middle-aged adults from the Healthy B...

Midlife hypertension increases risk for dementia. Around one third of adults have diagnosed hypertension; however, many adults are undiagnosed, or remain hypertensive despite diagnosis or treatment. Since blood pressure (BP) follows a circadian rhythm, ambulatory BP monitoring allows for the assessment of BP over a 24-hour period and provides an im...

Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort. The sleep regularity index (SRI) was calculated as...

Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort. The sleep regularity index (SRI) was calculated as...

Importance: Good sleep is essential for health, yet associations between sleep and dementia risk remain incompletely understood. The Sleep and Dementia Consortium was established to study associations between polysomnography (PSG)-derived sleep and the risk of dementia and related cognitive and brain magnetic resonance imaging endophenotypes. Obj...

Background Enlarged perivascular spaces (ePVS) and sleep disturbances have been associated with incident dementia. While healthy sleep is suggested to promote glymphatic clearance in the brain, poorer sleep may be associated with higher ePVS burden (representing impaired perivascular drainage), which may contribute to sleep’s role in dementia risk....

Background High levels of perceived stress are associated with an increased risk of late‐life dementia. As such, it is important to investigate resources that might protect against the negative effects of stress, particularly in midlife when dementia is still preventable. One potential resource is an individual’s psychological resilience (i.e., the...

Background In 40% of cases, dementia can be attributed to potentially modifiable risk factors (RFs) such as poor vascular health, poor sleep, low mood, and low social/cognitive engagement. ¹ BetterBrains (betterbrains.org.au) is a prospective, blinded endpoint, 24‐month randomised controlled trial to test the effectiveness of an online, person‐cent...

Background Both short and long sleep duration were previously associated with incident dementia, but underlying mechanisms of this association remains unknown. This project aims to evaluate how self‐reported sleep duration and its change over time associate with (A)myloid, (T)au, (N)eurodegeneration and (V)ascular neuroimaging markers of Alzheimer’...

Background Plasma NfL is a promising fluid biomarker for risk stratification and quantifying the extent of neuronal injury in conditions such as vascular cognitive impairment and dementia (VCID) and Alzheimer’s dementia. However, systemic factors such as kidney function can affect circulating levels and this requires further investigation to ensure...

Objective: To calibrate cognitive assessment data across multiple waves of the Framingham Heart Study (FHS), addressing study design considerations, ceiling effects, and measurement precision. Method: FHS participants completed several cognitive assessments including screening instruments and more comprehensive batteries at different study visit...

Background Irregular sleep-wake timing may cause circadian disruption leading to several chronic age-related diseases. We examined the relationship between sleep regularity and risk of all-cause, cardiovascular disease (CVD), and cancer mortality in 88,975 participants from the prospective UK Biobank cohort. Methods The sleep regularity index (SRI)...

Objective: Studies of modifiable dementia risk factors (MDRFs) generally consider MDRFs individually, despite strong evidence that they co-occur in adult populations. In a large sample of middle-aged adults, this study aimed to determine the frequency and co-occurrence of MDRFs, spanning five domains (mood symptomatology, risky lifestyle behaviors...

Background: Nocturnal hypoxemia may better capture disease burden than obstructive sleep apnea (OSA). Using a subset of participants from the Atherosclerosis Risk in Communities (ARIC) study who participated in the Sleep Heart Health Study (SHHS), we examined the association of nocturnal hypoxemia and OSA with cardiovascular diseases (CVD) and mort...

Background Recent data suggest that dementia incidence is declining. We investigated whether similar secular trends consisting of increasing size of brain structures and improving memory performance could be simultaneously occurring as a possible explanation. Method The Framingham Heart Study is a 3 generation, longitudinal study that includes cogn...

Background: Insomnia is one of the most common sleep disorders yet its relationship to the biology of Alzheimer's disease remains equivocal. Objective: We investigated the cross-sectional relationship between insomnia symptom severity and cerebrospinal fluid (CSF) concentrations of Alzheimer's disease biomarkers in a cognitively unimpaired middl...

Objective This meta-analysis of randomized controlled trials (RCTs) evaluates if treating sleep disturbances improves cognitive function over at least 12 weeks. Methods Multiple data sources were searched until November 1, 2021. RCTs were included if they examined the effect of an intervention (behavioral or medical) on sleep and cognition in an a...

Amyloid production increases during wakefulness before being cleared during sleep. Insomnia is one of the commonest sleep disorders, yet its relationship to core markers of preclinical Alzheimer’s disease remains unknown. We investigated the cross‐sectional relationship between insomnia symptom severity, APOE e4 carriage, and cerebrospinal spinal f...

Expression of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis, co‐localizes with neuropathology in the brain. Blood‐derived levels of GFAP have been associated with cognitive decline and dementia status. However, further examinations at a population‐based level are necessary to broaden generalizability and assess the bioma...

Both short and long sleep durations have been associated with an increased risk of future dementia [1, 2]. Transitioning to long sleep duration may be a marker of ongoing neurodegeneration [1]. However, the mechanisms linking short sleep time to dementia risk are unclear; short sleep duration may directly relate to Alzheimer’s Disease (AD) patholog...

Psychological stress is a potential modifiable risk factor for cognitive decline. However, the extent to which self-reported psychological stress is differentially associated with decline in specific cognitive domains remains unclear. Differences may be due to heterogeneity in the aspects of psychological stress investigated, for example, neurotici...

Characterization of the contribution of modifiable risk factors (MRF) to dementia generally consider MRFs individually, despite strong evidence that MRFs co‐occur. In a large group of middle‐aged adults, the prevalence and co‐occurrence of MRFs for dementia was determined, spanning five broad domains (mood, lifestyle behaviours (e.g., physical inac...

Background: The BetterBrains Randomized Controlled Trial (RCT) will evaluate the effectiveness of an online, person-centered, risk factor management, coaching intervention in community-dwelling, healthy adults at risk of cognitive decline. Multi-component interventions are challenging to evaluate due to program complexity and personalization to in...

Background While healthy sleep is suggested to promote glymphatic clearance in the brain, poorer sleep may be associated with higher enlarged perivascular spaces (ePVS) burden, potentially representing impaired perivascular drainage. This study aims to evaluate the association between ePVS burden and polysomnographic sleep characteristics in a larg...

Objective: Expression of glial fibrillary acidic protein (GFAP), a marker of reactive astrocytosis, colocalizes with neuropathology in the brain. Blood levels of GFAP have been associated with cognitive decline and dementia status. However, further examinations at a population-based level are necessary to broaden generalizability to community sett...

Study objectives We evaluated if self-reported sleepiness was associated with neuroimaging markers of brain aging and ischemic damage in a large community-based sample. Methods Participants from the Framingham Heart Study Offspring cohort (n=468, 62.5±8.7, 49.6%M) free of dementia, stroke, and neurological diseases, completed sleep questionnaires...

Background: Pragmatic biomarkers of preclinical dementia would allow for easy and large-scale screening of risk in populations. Physical function measures like grip strength and gait speed are potential predictive biomarkers but their relationship with plasma markers of Alzheimer's Disease and neurodegeneration have not been elucidated. Objective...

Background and objectives: The association between vascular risk factors and dementia varies with age making generalisability of dementia risk prediction rules to individuals of different ages challenging. We determined the most important vascular risk factors for inclusion in age-specific dementia risk scores. Methods: Framingham Heart Study Or...

Poststroke cognitive impairment and dementia (PSCID) is a major source of morbidity and mortality after stroke worldwide. PSCID occurs as a consequence of ischemic stroke, intracerebral hemorrhage, or subarachnoid hemorrhage. Cognitive impairment and dementia manifesting after a clinical stroke is categorized as vascular even in people with comorbi...

Background Sleep medications may contribute to dementia development or indicate sleep disturbances that are markers of or contributors to neurologic disease. The objective of this study was to examine the use of sleep medications and incident dementia in a community-based cohort of older adults. We hypothesize late-life sleep medication use is asso...

Circulating total-tau levels can be used as an endophenotype to identify genetic risk factors for tauopathies and related neurological disorders. Here, we confirmed and better characterized the association of the 17q21 MAPT locus with circulating total-tau in 14,721 European participants and identified three novel loci in 953 African American parti...

Importance: Up to 40% of dementia cases are potentially preventable; therefore, it is important to identify high-risk groups to whom resources could be targeted for maximal impact in preventing late-life dementia. The association of neighborhood-level socioeconomic status (SES) with cognition and dementia risk is not well known, particularly in mi...

Introduction: Engagement in cognitively stimulating work and activities may slow cognitive decline and dementia. We examined the individual and combined associations of four cognitive engagement indices (educational attainment, occupational complexity, social engagement, and cognitively stimulating leisure activities) with objective and subjective...

Background: Midlife cardiovascular risk factors (CVRF) are associated with reduced cognition and an increased risk of dementia. Objective: To further investigate this association using remote unsupervised online assessment of cognition and cardiovascular risk in middle-aged adults; and to explore the extent to which the association is altered by...

Background Residing in areas of low socioeconomic advantage is associated with increased risk of dementia ¹ and associated brain pathology 2,3 . Given the long and insidious course of dementia pathologies, it is critical to establish the effect of ‘exposomic’ risk factors in midlife and to understand which groups of people are particularly vulnerab...

Background Engagement in cognitively stimulating work and activities is proposed to slow cognitive decline and delay dementia. Few studies have considered the cumulative effect of multiple cognitively engaging factors on cognitive function. In middle‐aged adults, this study aimed to determine the individual and combined associations of four cogniti...

Background With no effective disease‐modifying treatments, there is a need to identify lifestyle risk factors that may prevent or delay the onset of dementia. One proposed risk factor is psychological stress. Although many studies have investigated the association between stress and dementia, to our knowledge, no meta‐analysis has examined this. Th...

Background Self‐reported sleep quality often does not strongly correlate with objective measurements of sleep, and thus, other factors such as cognitive ability might contribute in the self‐awareness of one’s own sleep. Although sleep disturbances are increasingly recognized as risk factor for dementia, individuals with lower cognitive performance...

Background Slow‐wave sleep (SWS) is the deepest sleep stage, and has been linked to many important physiological functions, including the cerebral metabolic clearance of toxins associated with Alzheimer’s disease. SWS loss might correlate with accelerated brain aging. However, older individuals and people with cognitive impairment have an impaired...

Background The extent to which modifiable and non‐modifiable risk factors contribute to cognitive decline in older people remains unclear. We sought to determine the association of modifiable and non‐modifiable components included in the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) score with memory decline and brain volume...

Background: In older adults, depressive and anxiety symptoms are associated with dementia risk, and represent a manifestation of the dementia prodrome. Understanding how these symptoms are related to cognition in midlife may inform risk models of dementia. Methods: This study examined the relationship between depressive and anxiety symptoms, and...

Flavonoids have shown anti-hypertensive and anti-atherosclerotic properties: the impact of habitual flavonoid intake on vascular function, central hemodynamics and arterial stiffness may be important. We investigated the relationship between habitual flavonoid consumption and measures of central blood pressure and arterial stiffness. We performed c...

Importance Cognitive resilience refers to the general capacity of cognitive processes to be less susceptible to differences in brain structure from age- and disease-related changes. Studies suggest that supportive social networks reduce Alzheimer disease and related disorder (ADRD) risk by enhancing cognitive resilience, but data on specific social...

Background: Although many studies have investigated the association between stress and risk of dementia, findings are inconsistent due to the variation in the measures used to assess stress. Objective: We conducted a systematic review and meta-analysis to investigate the association between psychological stress (including neuroticism, stressful...

Introduction: We evaluated whether insomnia symptom severity was associated with cognitive function, and whether this relationship was modified by biomarkers associated with Alzheimer's disease risk. Methods: We examined insomnia symptoms and neuropsychological performance 3.4 years later in 511 dementia-free Framingham Heart Study participants...

Background: Adherence to the Mediterranean-DASH for Neurodegenerative Delay (MIND) diet has previously been associated with cognitive decline and dementia. To our knowledge, no prior study has investigated the association between the MIND diet and measures of brain volume, silent brain infarcts (SBIs), or brain atrophy. Objective: We evaluated w...

Study objectives To examine if sleep symptomatology was associated with subjective cognitive concerns or objective cognitive performance in a dementia-free community-based sample. Methods A total of 1421 middle-aged participants (mean±standard deviation = 57±7; 77% female) from the Healthy Brain Project completed the Pittsburgh Sleep Quality Index...

Objective/Background Sleep-wake dysfunction is bidirectionally associated with the incidence and evolution of acute stroke. It remains unclear whether sleep disturbances are transient post-stroke or are potentially enduring sequelae in chronic stroke. Here, we characterize sleep architectural dysfunction, sleep-respiratory parameters, and hemispher...

Background: The apolipoprotein E (APOE) ɛ4 allele is associated with dose-response effects on cognitive dysfunction and dementia risk in older adults. However, its effects on cognition in middle-aged adults remains unclear. Objective: We examined effects of ɛ4 heterozygosity and homozygosity on objective and subjective cognition in middle-aged a...

Because of their roles as potential risk factors, we evaluated whether obstructive sleep apnea (OSA) severity interacts with interleukin-6 (IL-6) in predicting incident dementia of the Alzheimer’s type (DAT). In 269 dementia-free participants, IL-6 and the apnea-hypopnea index (AHI) were measured at baseline and incident DAT was surveilled for up t...

Objective To test the hypothesis that reduced slow-wave sleep, or N3 sleep, which is thought to underlie the restorative functions of sleep, is associated with MRI markers of brain aging, we evaluated this relationship in the community-based Framingham Heart Study Offspring cohort using polysomnography and brain MRI. Methods We studied 492 partici...

Background Sleepiness has been associated with an increased risk of Alzheimer’s disease (AD) and vascular dementia, but few studies have investigated its association with markers of accelerated brain aging. We evaluated the association between sleepiness and MRI measures; and whether the apolipoprotein E4 ( APOE4 ) allele status moderates this rela...

Background Sleep disturbance is common in dementia, although it is unclear whether changes in sleep architecture precede dementia onset. We examined the prospective association of changes in sleep architecture with the risk of incident Alzheimer’s disease (AD) dementia in the community‐based Framingham Heart Study (FHS). Methods Our sample compris...

Background Shorter rapid‐eye movement (REM) sleep has been associated with an increased risk of Alzheimer’s disease (AD) and accelerated cognitive decline. In this study, we evaluated the association between REM sleep duration and brain structure in adults without stroke or dementia; and whether the presence of an apolipoprotein E4 ( APOE4 ) allele...

Background YKL40 is expressed in reactive astrocytes and microglia and is upregulated in numerous neurological conditions associated with heightened neuroinflammation. We explored the utility of circulating YKL40 as a biomarker of accelerated brain aging and subclinical brain injury. Method YKL40 was measured using the Mesoscale Discovery (MSD) mu...

Background Web‐based platforms are used increasingly to assess cognitive function in unsupervised settings. However, methods for ensuring the validity of cognitive data arising from unsupervised assessments are limited. We applied Human Computer Interaction (HCI) concepts of acceptability and usability to examine the validity of unsupervised cognit...

Study objectives: Sleep-wake dysfunction is bidirectionally associated with the pathogenesis and evolution of stroke. Longitudinal and prospective measurement of sleep after chronic stroke remains poorly characterised due to a lack of validated objective and ambulatory sleep measurement tools in neurological populations. This study aimed to valida...

Background GDF15 (growth differentiation factor 15) and NT‐proBNP (N‐terminal pro‐B‐type natriuretic peptide) may offer promise as biomarkers for cognitive outcomes, including dementia. We determined the association of these biomarkers with cognitive outcomes in a community‐based cohort. Methods and Results Plasma GDF15 (n=1603) and NT‐proBNP leve...

Study Objectives To determine whether C-reactive protein (CRP), a marker of systemic inflammation, moderates the association between sleep and incident dementia. Methods We studied Framingham Heart Study participants who completed at baseline a serum CRP assessment and in-home polysomnography to measure sleep duration, sleep efficiency, sleep late...

Objective To determine the joint role of ideal cardiovascular health (CVH) and genetic risk on risk of dementia. Methods We categorized CVH based on the American Heart Association Ideal CVH Index and genetic risk through a genetic risk score (GRS) of common genetic variants as well as the APOE e4 genotype in 1,211 Framingham Heart Study (FHS) offs...

Objective To determine changes in the incidence of dementia between 1988 and 2015. Methods This analysis was performed in aggregated data from individuals >65 years in seven population-based cohort studies in the United States and Europe from the Alzheimer Cohort Consortium. First, we calculated age- and sex-specific incidence rates for all-cause...

Introduction: Web-based platforms are used increasingly to assess cognitive function in unsupervised settings. The utility of cognitive data arising from unsupervised assessments remains unclear. We examined the acceptability, usability, and validity of unsupervised cognitive testing in middle-aged adults enrolled in the Healthy Brain Project. Me...

Introduction Both sleep disturbances and inflammation are potential risk factors for Alzheimer’s disease (AD). However, it is unknown how inflammation and sleep interact together to influence the risk of developing AD dementia. Our objective was to evaluate whether interleukin-6 (IL-6) levels interact with sleep disturbances when predicting inciden...

Introduction Long sleep duration in aging populations has recently been proposed as a key modifiable risk factor and sequela of stroke. It is unclear whether the pathogenesis of post-stroke sleep-wake dysfunction is due to focal infarction to regional sleep-wake hubs in the brain, or to accelerated whole-brain neurodegeneration. We utilise a novel...

Sleep-wake disruption is a key modifiable risk factor and sequela of stroke. The pathogenesis of post-stroke sleep dysfunction is unclear. It is not known whether post-stroke sleep pathology is due to focal infarction to sleep-wake hubs, or to accelerated post-stroke neurodegeneration in subcortical structures after stroke. We characterise the firs...

Background: We determined the association between ratios of plasma ceramide species of differing fatty-acyl chain lengths and incident dementia and Alzheimer's disease (AD) dementia in a large, community-based sample. Methods: We measured plasma ceramide levels in 1892 [54% women, mean age 70.1 (SD 6.9) yr.] dementia-free Framingham Offspring St...

Sleep disturbances are common in dementia, including dementia due to Alzheimer's disease (AD). The discovery of the glymphatic system, optimized during sleep, has propelled interest in the role of sleep in amyloid beta dynamics and AD pathophysiology. Mechanistic studies suggest that both wakefulness and disrupted slow-wave sleep relate to an acute...

Background Dementia is a major health concern for which prevention and treatment strategies remain elusive. Lowering high blood pressure with specific antihypertensive medications (AHMs) could reduce the burden of disease. We investigated whether specific AHM classes reduced the risk for dementia.Methods We did a meta-analysis of individual partici...

Objective: To test the hypothesis that the inflammatory marker plasma soluble CD14 (sCD14) associates with incident dementia and related endophenotypes in 2 community-based cohorts. Methods: Our samples included the prospective community-based Framingham Heart Study (FHS) and Cardiovascular Health Study (CHS) cohorts. Plasma sCD14 was measured a...

Objective: To determine whether vascular risk factor burden in mid- or late-life associates with postmortem vascular and neurodegenerative pathologies in a community-based sample. Methods: We studied participants from the Framingham Heart Study who participated in our voluntary brain bank program. Overall vascular risk factor burden was calculat...

Background: Dementia is a major health concern for which prevention and treatment strategies remain elusive. Lowering high blood pressure with specific antihypertensive medications (AHMs) could reduce the burden of disease. We investigated whether specific AHM classes reduced the risk for dementia. Methods: We did a meta-analysis of individual p...

The burden of dementia is increasing globally. In the absence of curative treatment, preventive strategies to delay or reduce progression of dementia are crucial. This relies on the identification of modifiable risk factors. The effects of dementia on sleep are well recognized; however, there is now growing evidence suggesting a bidirectional relat...

Objective: To determine the association between plasma insulin-like growth factor binding protein 2 (IGFBP-2) and cognitive outcomes. Methods: We measured plasma IGFBP-2 levels in 1596 (53% women, mean age 68.7 [SD 5.7] years) dementia-free Framingham Offspring cohort participants between 1998 and 2001. Multivariable Cox proportional hazards mod...

Background: The apolipoprotein E (APOE) gene ɛ4 allele is a risk factor for Alzheimer's disease and cardiovascular disease. However, its relationship with cognition and brain volume after stroke is not clear. Objective: We compared cognition and medial temporal lobe volumes in APOEɛ4 carriers and non-carriers in the first year after ischemic str...

Higher plasma total‐tau level is associated with incident dementia but its relationship with stroke risk is unknown. In this prospective community‐based study, we evaluated plasma total‐tau level as a biomarker of stroke risk in 2794 Framingham Heart Study participants. Persons with plasma total‐tau levels in the top quintile, versus the bottom fou...