Publications by authors named "Matthew P Pase"

Background: Plasma and cerebrospinal (CSF) biomarkers are promising candidates for detecting neuropathology. While CSF biomarkers directly reflect pathophysiological processes within the central nervous system, their requirement for a lumbar puncture is a barrier to their widespread scalability in practice. Therefore, we examined cross-sectional associations of plasma biomarkers of amyloid (Aβ42/Aβ40 and pTau-181), neurodegeneration (Neurofilament Light, NfL), and neuroinflammation (Glial Fibrillary Acidic Protein, GFAP) with brain volume, cognition, and their corresponding CSF levels.

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Background: Disrupted sleep patterns have been shown to exacerbate Alzheimer's disease (AD) risk, potentially because of sleep's role in memory consolidation and synaptic plasticity. Recent evidence highlights that high brain-derived neurotrophic factor (BDNF) levels, a protein enabling neuroplasticity and memory functions, could play a protective role in age related cognitive impairment. We examined the association between total sleep time and cognition, and BDNF levels as a potential modifier.

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Background: In older adults, greater amyloid (Aβ) and tau positron emission tomography (PET) binding is associated with cognitive decline and dementia. However, the association of early amyloid and tau PET accumulation with cognition at midlife remains unclear. The goal of the current study was to evaluate the associations of Aβ and tau PET with cognition in a predominately middle-aged community-based cohort, as well as to examine the factors that may modify these associations.

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Background: Growing evidence shows neurovascular dysfunction occurs early in Alzheimer's disease (AD) and may be a useful early marker of pathology. Blood-brain barrier water exchange rate (BBB kw) is a novel measure of fluid transport through the neurovascular unit. Lower BBB kw has been associated with vascular risk factors, but its relationship with age, vascular brain health and biomarkers of AD remains equivocal.

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Background: Short sleep duration, low physical activity and high sedentary time are associated with higher dementia risk. To date, previous studies have considered these behaviors in isolation, and not as inter-related behaviors part of the 24-h day. Compositional data analysis (CoDA) treats these behaviors as inter-related within a constrained 24hrs.

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Background: The BetterBrains Trial is a prospective behavior-modification blinded endpoint randomized controlled trial to delay cognitive decline in middle-aged adults (aged 40-70) with a family history of dementia. The primary outcome is absence of decline on at-least one out of four cognitive tests at 24-months. We present trial recruitment and current participant completion statistics and baseline demographic, modifiable dementia risk factor (MDRF) and cognitive characteristics of the randomized sample, blinded to intervention arm.

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Background: Socioeconomic factors have an impact on long-term neurovascular health. Education attainment (EA) is a socioeconomic factor which may be related to vascular risk factors and brain health. We investigated the relation of EA and cerebral small vessel disease (CSVD) in community dwelling participants free of stroke and dementia.

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Introduction: We investigated whether depression modified the associations between sleep duration and cognitive performance.

Methods: Multivariable linear regression models examined the associations between sleep duration and cognition in 1,853 dementia- and stroke-free participants from the Framingham Heart Study. Participants were categorized in four groups: no depressive symptoms, no antidepressants; depressive symptoms without antidepressants use; antidepressant use without depressive symptoms; both depressive symptoms and antidepressant use.

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Article Synopsis
  • Short sleep duration is linked to cognitive impairment and dementia, particularly worsened by hypertension.
  • A study involving 682 participants found that those with hypertension showed a decline in executive functioning and an increase in brain injury with shorter sleep.
  • The relationship between sleep and cognitive performance was not observed in participants without hypertension, highlighting the importance of managing sleep and blood pressure for brain health.
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Background: Associations of plasma total tau levels with future risk of AD have been described.

Objective: To examine the extent to which plasma tau reflects underlying AD brain pathology in cognitively healthy individuals.

Methods: We examined cross-sectional associations of plasma total tau with 11C-Pittsburgh Compound-B (PiB)-PET and 18F-Flortaucipir (FTP)-PET in middle-aged participants at the community-based Framingham Heart Study.

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Dementia disproportionately affects individuals from disadvantaged backgrounds, including those living in areas of lower neighborhood-level socioeconomic status. It is important to understand whether there are specific neighborhood characteristics associated with dementia risk factors and cognition which may inform dementia risk reduction interventions. We sought to examine whether greenspace, walkability, and crime associated with the cumulative burden of modifiable dementia risk factors and cognition.

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Importance: Human brain development and maintenance is under both genetic and environmental influences that likely affect later-life dementia risk.

Objective: To examine environmental influences by testing whether time-dependent secular differences occurred in cranial and brain volumes and cortical thickness over birth decades spanning 1930 to 1970.

Design, Setting, And Participants: This cross-sectional study used data from the community-based Framingham Heart Study cohort for participants born in the decades 1930 to 1970.

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Background And Objectives: Higher YKL-40 levels in the CSF are a known biomarker of brain inflammation. We explored the utility of plasma YKL-40 as a biomarker for accelerated brain aging and dementia risk.

Methods: We performed cross-sectional and prospective analyses of 4 community-based cohorts in the United States or Europe: the Age, Gene/Environment Susceptibility-Reykjavik Study, Atherosclerosis Risk in the Communities study, Coronary Artery Risk Development in Young Adults study, and Framingham Heart Study (FHS).

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Accumulating evidence supports a link between sleep disorders, disturbed sleep, and adverse brain health, ranging from stroke to subclinical cerebrovascular disease to cognitive outcomes, including the development of Alzheimer disease and Alzheimer disease-related dementias. Sleep disorders such as sleep-disordered breathing (eg, obstructive sleep apnea), and other sleep disturbances, as well, some of which are also considered sleep disorders (eg, insomnia, sleep fragmentation, circadian rhythm disorders, and extreme sleep duration), have been associated with adverse brain health. Understanding the causal role of sleep disorders and disturbances in the development of adverse brain health is complicated by the common development of sleep disorders among individuals with neurodegenerative disease.

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Article Synopsis
  • The study aimed to analyze the relationship between self-reported sleep duration and neuroimaging markers related to Alzheimer's disease, focusing on amyloid, tau, neurodegeneration, and vascular factors.
  • It utilized data from participants in the Framingham Heart Study who underwent various imaging tests, assessing their sleep duration categorized into short, average, and long at two different times: at the testing point and approximately 13 years prior.
  • The results indicated no significant direct link between sleep duration and neuroimaging measures; however, long-term changes to longer sleep duration were associated with increased brain damage markers, while consistently long sleepers showed lower levels of brain damage compared to those with average sleep duration.
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  • Irregular sleep patterns could raise the risk of developing dementia, but the link hasn’t been fully understood; this study explores how day-to-day sleep consistency affects dementia risk and brain health.
  • Analyzing data from 88,094 participants in the UK Biobank, researchers calculated a Sleep Regularity Index (SRI) to evaluate sleep consistency and employed Cox models to assess its connection to dementia cases over about 7 years.
  • Results showed that both very low and very high levels of sleep regularity were linked to increased dementia risk, suggesting that maintaining a moderate level of sleep regularity might help reduce dementia risk.
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The neurovascular unit (NVU) is a complex structure that facilitates nutrient delivery and metabolic waste clearance, forms the blood-brain barrier (BBB), and supports fluid homeostasis in the brain. The integrity of NVU subcomponents can be measured in vivo using magnetic resonance imaging (MRI), including quantification of enlarged perivascular spaces (ePVS), BBB permeability, cerebral perfusion and extracellular free water. The breakdown of NVU subparts is individually associated with aging, pathology, and cognition.

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Article Synopsis
  • Irregular sleep-wake patterns can disrupt circadian rhythms and may increase the risk of death from all causes, cardiovascular disease, and cancer, according to a study of nearly 89,000 participants from the UK Biobank.
  • Researchers assessed sleep regularity using a Sleep Regularity Index (SRI) derived from activity data, with lower SRI scores indicating less regular sleep schedules.
  • The study found that individuals with highly irregular sleep (lowest SRI) had a significantly higher risk of mortality, while those with more consistent sleep patterns (highest SRI) showed lower mortality risk, emphasizing the importance of sleep regularity for health.
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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 examine whether Alzheimer disease genetic risk or hippocampal volumes suggestive of early neurodegeneration were associated with SWS loss.

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Article Synopsis
  • Psychological stress may be linked to dementia risk, but the exact mechanisms are not well understood.
  • A study involving 73 cognitively healthy middle-aged adults found no significant relationship between self-reported psychological stress and key Alzheimer’s disease biomarkers in cerebrospinal fluid.
  • The study noticed small effect sizes in the results and called for further research, especially since participants reported generally low stress levels.
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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 community-based Framingham Heart Study (FHS).

Methods: FHS participants aged at least 50 years free of stroke, cognitive impairment, and dementia at the time of MRI were included.

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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.

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Article Synopsis
  • * The study analyzed data from 5 US population cohorts with nearly 6,000 participants to examine how sleep measures correlate with cognitive functioning over a period of 5 years.
  • * Results indicated that better sleep quality is associated with improved cognitive performance, supporting the idea that good sleep may help reduce dementia risk as people age.
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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 important tool for improving the diagnosis and management of hypertension.

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