Examining early cerebral amyloid beta and tau accumulation in association with cognition in a predominantly middle‐aged cohort.

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.

Associations of cerebral amyloid beta and tau with cognition from midlife.

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 relationships.

Methods: C-Pittsburgh compound B amyloid and F-flortaucipir tau PET imaging were performed.

Association of Loneliness with Functional Connectivity MRI, Amyloid-β PET, and Tau PET Neuroimaging Markers of Vulnerability for Alzheimer's Disease.

Background: Loneliness has been declared an "epidemic" associated with negative physical, mental, and cognitive health outcomes such as increased dementia risk. Less is known about the relationship between loneliness and advanced neuroimaging correlates of Alzheimer's disease (AD).

Objective: To assess whether loneliness was associated with advanced neuroimaging markers of AD using neuroimaging data from Framingham Heart Study (FHS) participants without dementia.

Nonalcoholic fatty liver disease, liver fibrosis, and structural brain imaging: The Cross-Cohort Collaboration.

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 study among dementia- and stroke-free individuals, data were pooled from the Offspring and Third Generation cohorts of the Framingham Heart Study (FHS), the Rotterdam Study (RS), and the Study of Health in Pomerania.

Associations of Pulmonary Function with MRI Brain Volumes: A Coordinated Multi-Study Analysis.

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 large community-based samples (N = 11,091) were analyzed.

Association of Aortic Stiffness and Pressure Pulsatility With Global Amyloid-β and Regional Tau Burden Among Framingham Heart Study Participants Without Dementia.

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 without dementia.

Design, Setting, And Participants: The sample for this cross-sectional study was drawn from the Framingham Heart Study Third Generation Cohort at examination 3 (N = 3171; 2016-2019), of whom 3092 successfully underwent comprehensive hemodynamic evaluations.

Determining Vascular Risk Factors for Dementia and Dementia Risk Prediction Across Mid- to Later Life: The Framingham Heart Study.

Background And Objectives: The association between vascular risk factors and dementia varies with age, making generalizability 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 Original and Offspring cohort participants with available data on the Framingham Stroke Risk Profile (FSRP) at midlife (age 55; n = 4,899, 57% women), late life (ages 65 or 70), or later life (ages 75 or 80 [n = 2,386, 62% women]) were followed for 10-year incident dementia risk from ages 65, 70, 75, and 80.

Estimating the causal effect of treatment with direct-acting antivirals on kidney function among individuals with hepatitis C virus infection.

Background: Direct-acting antivirals (DAA) are highly effective at treating Hepatitis C virus (HCV) infection, with a cure rate >95%. However, the effect of DAAs on kidney function remains debated.

Methods: We analyzed electronic health record data for DAA-naive patients with chronic HCV infection engaged in HCV care at Boston Medical Center between 2014 and 2018.

Blood Phosphorylated Tau 181 as a Biomarker for Amyloid Burden on Brain PET in Cognitively Healthy Adults.

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 were measured at baseline in 52 [48% women, mean 64.

Menopause Status Moderates Sex Differences in Tau Burden: A Framingham PET Study.

Objective: Women have a higher lifetime risk of Alzheimer's disease (AD) than men. Among cognitively normal (CN) older adults, women exhibit elevated tau positron emission tomography (PET) signal compared with men. We explored whether menopause exacerbates sex differences in tau deposition in middle-aged adults.

Non-Alcoholic Fatty Liver Disease, Liver Fibrosis, and Regional Amyloid-β and Tau Pathology in Middle-Aged Adults: The Framingham Study.

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 (Aβ) and tau pathology.

Methods: The study sample included Framingham Study participants from the Offspring and Third generation cohorts who attended exams 9 (2011-2014) and 2 (2008-2011), respectively.

Associations Between Brainstem Volume and Alzheimer's Disease Pathology in Middle-Aged Individuals of the Framingham Heart Study.

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. Lower volume of the medulla, pons, or midbrain was associated with greater neocortical amyloid burden.

Association of Loneliness With 10-Year Dementia Risk and Early Markers of Vulnerability for Neurocognitive Decline.

Background And Objectives: 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 dementia risk and early cognitive and neuroanatomic imaging markers of ADRD vulnerability.

Association of Social Support With Brain Volume and Cognition.

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 support mechanisms are sparse.

Objective: To examine the association of individual forms of social support with a global neuroanatomical measure of early ADRD vulnerability and cognition.

Mind Diet Adherence and Cognitive Performance in the Framingham Heart Study.

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 whether adherence to the MIND diet associated with superior cognitive function, larger brain volumes, fewer SBIs, and less cognitive decline in the community-based Framingham Heart Study.

Herpes Labialis, Chlamydophila pneumoniae, Helicobacter pylori, and Cytomegalovirus Infections and Risk of Dementia: The Framingham Heart Study.

Background: An association between chronic infectious diseases and development of dementia has been suspected for decades, based on the finding of pathogens in postmortem brain tissue and on serological evidence. However, questions remain regarding confounders, reverse causality, and how accurate, reproducible and generalizable those findings are.

Objective: Investigate whether exposure to Herpes simplex (manifested as herpes labialis), Chlamydophila pneumoniae (C.

Association of Midlife Depressive Symptoms with Regional Amyloid-β and Tau in the Framingham Heart Study.

Background: Depressive symptoms predict increased risk for dementia decades before the emergence of cognitive symptoms. Studies in older adults provide preliminary evidence for an association between depressive symptoms and amyloid-β (Aβ) and tau accumulation. It is unknown if similar alterations are observed in midlife when preventive strategies may be most effective.

Bone Mineral Density Measurements and Association With Brain Structure and Cognitive Function: The Framingham Offspring Cohort.

Background: Bone mineral density (BMD) is a potential surrogate marker of lifetime estrogen exposure previously linked to increased risk of Alzheimer dementia among elderly women. We examine the association between BMD in the "young old" with imaging biomarkers of brain aging and cognitive performance.

Methods: Offspring participants (N=1905, mean age 66) of a population-based cohort who had BMD, brain imaging and detailed cognitive assessment were included in the study.

Associations of the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay diet with cardiac remodelling in the community: the Framingham Heart Study.

Normal cardiac function is directly associated with the maintenance of cerebrovascular health. Whether the Mediterranean-Dietary Approaches to Stop Hypertension Intervention for Neurodegenerative Delay (MIND) diet, designed for the maintenance of neurocognitive health, is associated with cardiac remodelling is unknown. We evaluated 2512 Framingham Offspring Cohort participants who attended the eighth examination cycle and had available dietary and echocardiographic data (mean age 66 years; 55 % women).

The cortical origin and initial spread of medial temporal tauopathy in Alzheimer's disease assessed with positron emission tomography.

Advances in molecular positron emission tomography (PET) have enabled anatomic tracking of brain pathology in longitudinal studies of normal aging and dementia, including assessment of the central model of Alzheimer's disease (AD) pathogenesis, according to which TAU pathology begins focally but expands catastrophically under the influence of amyloid-β (Aβ) pathology to mediate neurodegeneration and cognitive decline. Initial TAU deposition occurs many years before Aβ in a specific area of the medial temporal lobe. Building on recent work that enabled focus of molecular PET measurements on specific TAU-vulnerable convolutional temporal lobe anatomy, we applied an automated anatomic sampling method to quantify TAU PET signal in 443 adult participants from several observational studies of aging and AD, spanning a wide range of ages, Aβ burdens, and degrees of clinical impairment.

Mid to Late Life Hypertension Trends and Cerebral Small Vessel Disease in the Framingham Heart Study.

The duration and lifetime pattern of hypertension is related to risk of stroke and dementia. In turn, cerebral small vessel disease (CSVD) is the most frequent form of cerebrovascular disease underlying dementia and stroke. Thus, study of the relation of mid to late life hypertension trends with CSVD late in life will help understand hypertension's role and inform preventive efforts of CSVD consequences.