Alexa Beiser

• PhD
• Professor (Full) at Boston University

BACKGROUND It is unclear how poststroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic and hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, and cryptogenic/other determined causes), and poststroke cognitive dec...

Background Advancing therapeutic and prevention strategies for vascular contributions to cognitive impairment and dementia (VCID) warrants identifying novel biomarkers. However, due to the high heterogeneity underlying dementia pathology, a single marker may not fully risk‐stratify for VCID. A blood‐based biomarker of neuroaxonal injury, neurofilam...

Background The residual approach has found wide application in researching cognitive resilience, a phenomenon conceptually understood as cognitive performance being better‐than‐typical for an individual, despite apparent AD pathology. The standard residual approach extracts information about an individual’s resilience from the residuals of a linear...

Background Plasma p‐tau biomarkers are promising diagnostic tools for widespread clinical use. However, recent studies have raised concerns regarding the effect of common medical comorbidities, such as cardiovascular disease (CVD), on plasma p‐tau specificity. These influences must be better understood to enable appropriate clinical use of p‐tau181...

Background Advancing therapeutic and prevention strategies for vascular contributions to cognitive impairment and dementia (VCID) warrants identifying novel biomarkers. However, due to the high heterogeneity underlying dementia pathology, a single marker may not fully risk‐stratify for VCID. A blood‐based biomarker of neuroaxonal injury, neurofilam...

Background Recent research suggests that soluble pathogenic tau accumulates in the brain microvasculature of patients with Alzheimer’s Disease (AD) and primary tauopathies, driving cerebrovascular impairments and further tau accumulation. However, little is known about the interplay of these processes before dementia onset. In the present study, we...

Background Higher Mediterranean‐ DASH for Neurodegenerative Delay (MIND) diet scores have previously been associated with larger total brain volume (TBV) in the Framingham Offspring Study (FOS) community‐based cohort. We investigated cross‐sectional relationships between the MIND diet and structural brain imaging volumes and white matter hyperinten...

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. Method We...

Background Dementia is a major contributor to loss of autonomy in the elderly. Every year spent with dementia results in significant medical and societal costs. Understanding secular trends of life expectancy with and without dementia would enable us to better anticipate future needs. To date, only a few studies have attempted to decipher the scena...

Background The MarkVCID consortium was established to address the paucity of biomarkers for vascular contributions to cognitive impairment and dementia (VCID), a leading cause of dementia. Plasma neurofilament light (NfL), a neuroaxonal injury marker elevated in several neurological and neurodegenerative diseases, was selected as one of the first b...

Background Peak‐width of skeletonized mean diffusivity (PSMD) is an emerging biomarker of cerebral small vessel disease (cSVD)‐related vascular contributions to cognitive impairment and dementia (VCID). Higher PSMD values reflect greater white matter microstructural damage, and prior research has related PSMD to sporadic and monogenic forms of cSVD...

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 cog...

Background Recent research has highlighted the importance of sleep on cognitive processes. However, conflicting evidence exists regarding optimal sleep duration and the impact of other co‐occurring conditions, such as depression. A diagnosis of depression in mid‐life may increase the risk of developing dementia. We examined the association between...

Background Apolipoprotein (Apo) E4, a main susceptibility gene for Alzheimer’s disease (AD) is associated with increased vascular dysfunction, amyloid pathology, and neurodegeneration. The effector pathways leading to increased vascular risk in ApoE4 carriers needs to be established. Platelet aggregation is a key marker of vascular dysfunction and...

INTRODUCTION Diffusion tensor image analysis along the perivascular space (DTI‐ALPS) index was proposed for assessing glymphatic clearance function. This study evaluated DTI‐ALPS as a biomarker for cerebral small vessel disease (cSVD) related vascular cognitive impairment and dementia (VCID). METHODS Four independent cohorts were examined. A compo...

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...

Objectives Late‐onset epilepsy has the highest incidence among all age groups affected by epilepsy and often occurs in the absence of known clinical risk factors such as stroke and dementia. There is increasing evidence that brain changes contributing to epileptogenesis likely start years before disease onset, and we aim to relate cognitive and ima...

Background: Mild manifestations of individual cerebral small vessel disease (CSVD) markers are common and may not denote increased risk, but high CSVD burden identifies individuals at increased risk of stroke and dementia. Scores incorporating multiple individual CSVD markers may better identify a person's risk. We related a multi-marker CSVD score...

Objective Subclinical vascular brain injury is an increasingly recognized risk factor for stroke and dementia. Despite well‐established sex differences in vascular risk and disease prevalence, the impact of sex on drivers of subclinical vascular brain injury remains unclear, presenting a barrier to developing sex‐specific prevention guidelines. We...

Background Midlife obesity is related to late-onset dementia. Studying adipose tissue-secreted adipokines in the context of brain aging may help us understand this association. Objective To investigate associations between adipokines and brain MRI markers in middle-aged adults from the Third-Generation cohort of the Framingham Heart Study. Method...

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. Here we performed genome-wide association studies meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and the ventral diencephalon)...

Although neuropsychological tests are commonly used in the evaluation of possible mild cognitive impairment (MCI), poor test scores may be indicative of factors other than neurological compromise. The current study assessed the role of lifelong reading disorder on MCI classification. Community dwelling older adults with a suspected developmental re...

Background Identifying nutrition- and lifestyle-based risk factors for cognitive impairment and dementia may aid future primary prevention efforts. Objective We aimed to examine the association of serum vitamin D levels with incident all-cause dementia, clinically characterized Alzheimer’s disease (AD), MRI markers of brain aging, and neuropsychol...

Subcortical brain structures are involved in developmental, psychiatric and neurological disorders. We performed GWAS meta-analyses of intracranial and nine subcortical brain volumes (brainstem, caudate nucleus, putamen, hippocampus, globus pallidus, thalamus, nucleus accumbens, amygdala and, for the first time, the ventral diencephalon) in 74,898...

INTRODUCTION We investigated the associations of leptin markers with cognitive function and magnetic resonance imaging (MRI) measures of brain atrophy and vascular injury in healthy middle‐aged adults. METHODS We included 2262 cognitively healthy participants from the Framingham Heart Study with neuropsychological evaluation; of these, 2028 also h...

INTRODUCTION: Dementia is a multifactorial disease with Alzheimer’s disease (AD) and vascular dementia (VaD) pathologies making the largest contributions. Yet, most genome-wide association studies (GWAS) focus on AD. METHODS: We conducted a GWAS of all-cause dementia (ACD) and examined the genetic overlap with VaD. Our dataset includes 800,597 indi...

INTRODUCTION Understanding early neuropathological changes and their associations with cognition may aid dementia prevention. This study investigated associations of cerebral amyloid and tau positron emission tomography (PET) retention with cognition in a predominately middle‐aged community‐based cohort and examined factors that may modify these re...

Background Higher midlife physical activity engagement has been associated with lower dementia risk in late life. However, the underlying mechanisms contributing to the protective effect remain unclear. Objective The goal of the current study was to evaluate the associations of physical activity with cerebral amyloid-β (Aβ) and tau in a predominat...

BACKGROUND A coordinated network of circulating inflammatory molecules centered on the pleotropic pro-atherogenic cytokine interleukin-18 (IL-18) is linked to cerebral small vessel disease. We sought to validate the association of this inflammatory biomarker network with incident stroke risk, cognitive impairment, and imaging metrics in a sample of...

Background: It is unclear how post-stroke cognitive trajectories differ by stroke type and ischemic stroke subtype. We studied associations between stroke types (ischemic, hemorrhagic), ischemic stroke subtypes (cardioembolic, large artery atherosclerotic, lacunar/small vessel, cryptogenic/other determined etiology), and post-stroke cognitive decli...

The size of the human head is highly heritable, but genetic drivers of its variation within the general population remain unmapped. We perform a genome-wide association study on head size (N = 80,890) and identify 67 genetic loci, of which 50 are novel. Neuroimaging studies show that 17 variants affect specific brain areas, but most have widespread...

Background and hypothesis It remains unclear if the relation of chronic kidney disease (CKD) with cognitive dysfunction is independent of blood pressure (BP). We evaluated kidney function in relation to premorbid BP measurements, cerebral small vessel disease (CSVD) and incident mild cognitive impairment (MCI) and dementia in Framingham Offspring C...

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....

Background and objectives: Neurotrophic factors (NTFs) play an important role in Alzheimer disease (AD) pathophysiology. Brain-derived neurotrophic factor (BDNF) and vascular endothelial growth factor (VEGF) are important NTFs. However, a direct link of BDNF and VEGF circulating levels with in vivo measures of amyloid-β (Aβ) and tau burden remains...

Introduction: Associations between stroke subtype and post-stroke cognitive decline are unclear. We determined if post-stroke cognitive trajectories differed between 1) hemorrhagic vs. ischemic stroke and 2) ischemic stroke subtypes. Methods: We identified 1,150 eligible dementia-free individuals with incident stroke (93% ischemic, 7% hemorrhagic,...

Introduction: We evaluated whether education level is associated with post-stroke cognitive decline and whether age modifies the association. Methods: We analyzed pooled data from 2,019 stroke survivors from the Atherosclerosis Risk in Communities, REasons for Geographic and Racial Differences in Stroke, Cardiovascular Health, and Framingham Offspr...

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/En...

INTRODUCTION Early risk stratification for clinical dementia could lead to preventive therapies. We identified and validated a magnetic resonance imaging (MRI) signature for Alzheimer's disease (AD) and related dementias (ARDR). METHODS An MRI ADRD signature was derived from cortical thickness maps in Framingham Heart Study (FHS) participants with...

Identifying circulating proteins associated with cognitive function may point to biomarkers and molecular process of cognitive impairment. Few studies have investigated the association between circulating proteins and cognitive function. We identify 246 protein measures quantified by the SomaScan assay as associated with cognitive function (p < 4.9...

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 Hypertension is the most potent stroke risk factor and is also related to cerebral small vessel disease. We studied the relation between mid-to-late-life hypertension trends and cerebral white matter injury in community-dwelling individuals from the FHS (Framingham Heart Study). METHODS FHS Offspring cohort participants with available m...

Background Preclinical studies highlight the importance of endogenous cannabinoids (endocannabinoids; eCBs) in neurodegeneration. Yet, prior observational studies focused on limited outcome measures and assessed only few eCB compounds while largely ignoring the complexity of the eCB system. We examined the associations of multiple circulating eCBs...

Background and purpose Prior studies reported conflicting findings regarding the association of nonalcoholic fatty liver disease (NAFLD) and liver fibrosis with measures of brain health. We examined whether NAFLD and liver fibrosis are associated with structural brain imaging measures in middle‐ and old‐age adults. Methods In this cross‐sectional...

Background Neurofilament light chain (NfL) is a marker of neuronal injury. Perivascular spaces (PVS) visible on magnetic resonance imaging (MRI) represent cerebral small vessel disease (CSVD) but their role as markers of neuronal injury needs further clarification. Objective To relate PVS burden according to brain topography and plasma NfL. Metho...

Introduction Cardiometabolic risk factors and epigenetic patterns, increased in physically inactive individuals, are associated with an accelerated brain aging process. Objective To determine whether cardiometabolic risk factors and epigenetic patterns mediate the association of physical inactivity with unfavorable brain morphology. Methods We in...

Background Free Water (FW), a Diffusion Tensor Imaging‐based biomarker kit has been demonstrated by the MarkVCID consortium to have excellent instrumental validity ¹ . We sought to determine its clinical relevance by investigating association of FW with clinically meaningful aspects of vascular contributions to cognitive impairment and dementia (VC...

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 Alzheimer’s disease (AD), the most common form of dementia, is a complex polygenic disease with genetic, cellular, pathologic, and clinical heterogeneity. Recently, significant attempts have been made for identifying AD biomarkers for reliably tracking disease progression in its early asymptomatic stages. To this end, amyloid PET imaging...

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...

Importance: Incident stroke is associated with accelerated cognitive decline. Whether poststroke vascular risk factor levels are associated with faster cognitive decline is uncertain. Objective: To evaluate associations of poststroke systolic blood pressure (SBP), glucose, and low-density lipoprotein (LDL) cholesterol levels with cognitive decli...

Amyloid PET imaging has been crucial for detecting the accumulation of amyloid beta (Aβ) deposits in the brain and to study Alzheimer’s disease (AD). We performed a genome-wide association study on the largest collection of amyloid imaging data (N = 13,409) to date, across multiple ethnicities from multicenter cohorts to identify variants associate...

Background and Objectives Previous studies suggest lower mitochondrial DNA (mtDNA) copy number (CN) is associated with neurodegenerative diseases. However, whether mtDNA CN in whole blood is related to endophenotypes of Alzheimer’s disease (AD) and AD related dementia (AD/ADRD) needs further investigation. We assessed the association of mtDNA CN wi...

We studied the association between inflammatory biomarkers and magnetic resonance imaging (MRI) visible perivascular spaces (PVS) in Framingham Heart Study participants free of stroke and dementia. PVS in the basal ganglia (BG) and centrum semiovale (CSO) were rated with validated methods and categorized based on counts. A mixed score of high PVS b...

Introduction: We investigated associations of obesity with the expression of Alzheimer's disease (AD)-related genes in a large community-based cohort. Methods: The sample consisted of 5619 participants from the Framingham Heart Study. Obesity metrics included body mass index (BMI) and waist-to-hip ratio (WHR). Gene expression was measured for a...

Women have a higher prevalence of dementia than men. We determined the association between female reproductive factors and risk of cognitive outcomes, including incident dementia, in a community‐based sample of cognitively healthy individuals. Lifetime reproductive factors including age of menarche, age of menopause, reproductive lifespan (age of m...

Insulin resistance (IR) is a major risk factor for Alzheimer’s disease (AD) and is primarily driven by obesity, another AD risk factor. The mechanism by which IR predisposes to AD is unknown. Epigenetic studies may help identify molecular signatures of IR associated with AD, thus contributing to an improved understanding of the biological and regul...

Neurofilament light chain (NfL) is a broad marker of neuroaxonal injury that is elevated in the CSF in those with vascular cognitive impairment and dementia (VCID). Blood and CSF levels highly correlate, making it an attractive peripheral marker for VCID pathology. As part of the MarkVCID consortium, we sought to evaluate the instrumental validity...

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...

As Alzheimer’s clinical trials shift earlier and earlier in the disease process, current global PET measures of beta‐amyloid (Aβ) positivity may be insufficient for detecting the earliest Aβ deposits. Regional PET measures may better detect the earliest deposits. Previous efforts to identify early‐accumulating regions have inferred which regions ma...

Nutritional factors can abet or protect against systemic chronic inflammation, which plays an important role in the development and progression of dementia. We evaluated whether higher (i.e. pro‐inflammatory) Dietary Inflammatory Index(DII) scores were associated with accelerated cognitive decline in the community‐based Offspring Framingham Heart S...

Background and Objectives Diet may be a key contributor to brain health in midlife. In particular, Omega-3 fatty acids have been related to better neurological outcomes in older adults. However, studies focusing on midlife are lacking. We investigated the cross-sectional association of red blood cell (RBC) Omega-3 fatty acid concentrations with MRI...

Background Previous studies suggest poor pulmonary function is associated with increased burden of cerebral white matter hyperintensities and brain atrophy among elderly individuals, but the results are inconsistent. Objective To study the cross-sectional associations of pulmonary function with structural brain variables. Methods Data from six la...

Methods: We used linear regression to examine cross-sectional associations of accelerometer-measured physical activity and sedentary time with extrinsic and intrinsic epigenetic age acceleration models (EEAA and IEAA) and GrimAge measured from blood samples from Framingham Heart Study participants with accelerometry and DNA methylation data (n = 2...

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...

Docosahexaenoic acid (DHA) might help prevent Alzheimer’s disease (AD). Red blood cell (RBC) status of DHA is an objective measure of long-term dietary DHA intake. In this prospective observational study conducted within the Framingham Offspring Cohort (1490 dementia-free participants aged ≥65 years old), we examined the association of RBC DHA with...

Importance: Aortic stiffness is associated with clinical hallmarks of Alzheimer disease and related dementias and could be a modifiable target for disease prevention. Objective: To assess associations of aortic stiffness and pressure pulsatility with global amyloid-β plaques and regional tau burden in the brain of middle-aged and older adults wi...

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...

Background Insulin-like growth factor 1 (IGF-1) signaling has been implicated in Alzheimer’s disease pathogenesis, and further evidence suggests inflammation can be a moderator of this association. However, most research to date has been conducted on older adults. Objective To investigate the association of serum IGF-1 and IGF binding protein 3 (I...

Cerebral small vessel disease is a leading cause of stroke and a major contributor to cognitive decline and dementia, but our understanding of specific genes underlying the cause of sporadic cerebral small vessel disease is limited. We report a genome-wide association study and a whole-exome association study on a composite extreme phenotype of cer...

Introduction: We investigated cross-sectional associations between the Dietary Inflammatory Index (DII) and measures of brain volume and cerebral small vessel disease among participants of the Framingham Heart Study Offspring cohort. Methods: A total of 1897 participants (mean ± standard deviation, age 62±9) completed Food Frequency Questionnair...

Blood biomarkers for dementia have the potential to identify preclinical disease and improve participant selection for clinical trials. Machine learning is an efficient analytical strategy to simultaneously identify multiple candidate biomarkers for dementia. We aimed to identify important candidate blood biomarkers for dementia using three machine...

Background Plasma phosphorylated-tau181 (p-tau181) is a promising biomarker for Alzheimer’s disease (AD) and may offer utility for predicting preclinical disease. Objective To evaluate the prospective association between plasma p-tau181 and amyloid-β (Aβ) and tau-PET deposition in cognitively unimpaired individuals. Methods Plasma p-tau181 levels...

Background: The remaining lifetime risk (RLR) is the probability of developing an outcome over the remainder of one's lifespan at any given age. The RLR for atherosclerotic cardiovascular disease (ASCVD) in three 20-year periods were assessed using data from a single community-based cohort study of predominantly White participants Methods: Longitud...

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...

A challenge in standard genetic studies is maintaining good power to detect associations, especially for low prevalent diseases and rare variants. The traditional methods are most powerful when evaluating the association between variants in balanced study designs. Without accounting for family correlation and unbalanced case-control ratio, these an...

Aim: To examine if the associations between vascular risk factors (VRF) and brain MRI measures of brain aging and cerebral small vessel disease are different in men and women. Background: Men and women differ in their propensity to develop stroke and this is reflected in sex-specific versions of the widely used Framingham Stroke Risk Prediction (FS...

Background Liver steatosis and fibrosis are emerging as risk factors for multiple extrahepatic health conditions; however, their relationship with Alzheimer’s disease pathology is unclear. Objective To examine whether non-alcoholic fatty liver disease (NAFLD) and FIB-4, a non-invasive index of advanced fibrosis, are associated with brain amyloid-β...

The brainstem is among the first regions to accumulate Alzheimer’s disease (AD)-related hyperphosphorylated tau pathology during aging. We aimed to examine associations between brainstem volume and neocortical amyloid-β or tau pathology in 271 middle-aged clinically normal individuals of the Framingham Heart Study who underwent MRI and PET imaging....

Background and Objective Loneliness is common and its prevalence is rising. The relationship of loneliness with subsequent dementia and the early preclinical course of Alzheimer disease and related dementia (ADRD) remains unclear. Thus, the primary objective of this study was to determine the association of loneliness with 10-year all-cause dementi...

Background The residual lifetime risk (RLR) of developing heart failure (HF) may have changed over time because of the increasing population burden of hypertension, obesity, and diabetes; greater survival after myocardial infarction; and a greater lifespan. Objectives The authors assessed changes in the RLR for HF in two 25-year epochs (1965-1989...

Background Epidermal growth factor containing fibulin extracellular matrix protein-1 (EFEMP1) has been associated with increased white matter hyperintensities (WMH) burden and disorders of premature aging and may have a shared pathophysiological role in the development of WMH and dementia. Objective To determine the association between plasma EFEM...

Background Nutrition is hypothesized to protect against systemic chronic inflammation, which plays an important role in the development and progression of disease including dementia. We evaluated whether higher (i.e. pro‐inflammatory) Dietary Inflammatory Index (DII) scores were associated with increased incidence of all‐cause dementia and Alzheime...

Background Nonalcoholic fatty liver disease (NAFLD) is the most common chronic liver condition. Accumulating evidence points to an association of NAFLD with cognitive impairment, brain aging and decreased brain activity, yet the association with Alzheimer’s disease is unclear. Evidence suggests that liver fibrosis, rather than the existence of hepa...

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 Cognitively‐normal (CN) older women exhibit elevated tau‐PET signal in medial temporal and neocortical regions compared with men. The effect of menopause on tau deposition remains unclear. We explored menopausal status as a moderator of sex differences in tau deposition in middle‐aged adults. Method 273 CN (Age=55yrs(±8), Female(n)=134,...

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 Plasma phospho‐tau181 is a promising new biomarker for Alzheimer’s disease (AD) with greater specificity than t‐tau and greater convenience compared to cerebrospinal fluid or neuroimaging biomarkers. However, its association with regional brain cortical amyloid and tau deposition is not well characterized. We evaluated 1) the association...

Background The Framingham Heart Study (FHS), a three‐generation community‐based cohort studying cardiovascular disease across the adult lifespan, has expanded to include positron emission tomography (PET) of beta‐amyloid (Aβ) and tau. Our aim is to characterize these pathologies in this unique sample and utilize the wide age range to assess the spa...

Background The brainstem consists of various nuclei that accumulate tau early in the Alzheimer’s disease (AD) trajectory. Previous studies discovered the genetic loci linked to brainstem volume, revealing genetic overlap with several neurological disorders, including AD. We aimed to investigate whether the volume of distinct parts of the brainstem...

Background Alzheimer’s disease (AD) starts decades before the onset of clinical symptoms, posing enormous challenges for the development and administration of timely treatments. Therefore, the development of robust AD biomarkers continues to be a high priority in the field. MRI‐derived measures are suitable, non‐invasive biomarkers in populations a...

Objective Stroke is the most common cause of epilepsy in older age. Subclinical cerebrovascular disease is believed to underlie some of the 30%–50% of late‐onset epilepsy without a known cause (Li et al. Epilepsia. 1997;38:1216; Cleary et al. Lancet. 2004;363:1184). We studied the role of modifiable vascular risk factors in predicting subsequent ep...

Introduction: Physical inactivity is associated with a higher risk of dementia, and has also been associated with unfavorable brain morphology. It is also clear that cardiometabolic risk factors accelerate the brain aging process. Hypothesis: Cardiometabolic risk factors mediate the association of physical inactivity with unfavorable brain morpholo...