A5005435770- Dementia and Cognitive Impairment Research
- Alzheimer's disease research and treatments
- Functional Brain Connectivity Studies
- Advanced Neuroimaging Techniques and Applications
- Neurological Disease Mechanisms and Treatments
- Health, Environment, Cognitive Aging
- Advanced MRI Techniques and Applications
- Memory and Neural Mechanisms
- Bioinformatics and Genomic Networks
- Medical Imaging Techniques and Applications
- Cancer-related cognitive impairment studies
- Intracerebral and Subarachnoid Hemorrhage Research
- Cerebrovascular and Carotid Artery Diseases
- Neural dynamics and brain function
- Amyloidosis: Diagnosis, Treatment, Outcomes
- Cholinesterase and Neurodegenerative Diseases
- Frailty in Older Adults
- Neuroinflammation and Neurodegeneration Mechanisms
- Tryptophan and brain disorders
- Parkinson's Disease Mechanisms and Treatments
- Blood Pressure and Hypertension Studies
- Mental Health Research Topics
- Neurological Disorders and Treatments
- Olfactory and Sensory Function Studies
- Nutritional Studies and Diet
Massachusetts General Hospital
2016-2025
Harvard University
2016-2025
Athinoula A. Martinos Center for Biomedical Imaging
2015-2024
Brigham and Women's Hospital
2015-2024
Maastricht University
2017-2023
Gordon Center for Medical Imaging
2021-2023
Cliniques Universitaires Saint-Luc
2021-2023
Alzheimer’s Disease Neuroimaging Initiative
2017-2023
Transnational University Limburg
2023
Florey Institute of Neuroscience and Mental Health
2017-2022
Objective Detection of focal brain tau deposition during life could greatly facilitate accurate diagnosis Alzheimer disease (AD), staging and monitoring progression, development disease‐modifying therapies. Methods We acquired positron emission tomography (PET) using 18 F T807 (AV1451), amyloid‐β PET 11 C Pittsburgh compound B (PiB) in older clinically normal individuals, symptomatic patients with mild cognitive impairment or AD dementia. Results found abnormally high cortical binding...
Positron emission tomography (PET) imaging now allows in vivo visualization of both neuropathologic hallmarks Alzheimer disease (AD): amyloid-β (Aβ) plaques and tau neurofibrillary tangles. Observing their progressive accumulation the brains clinically normal older adults is critically important to understand pathophysiologic cascade leading AD inform choice outcome measures prevention trials.To assess associations among Aβ, tau, cognition, measured during different observation periods for 7...
Gray matter brain structures, including deep nuclei and the cerebral cortex, are affected significantly early in course of multiple sclerosis these changes may not be directly related to demyelinating white lesions. The hippocampus is an archicortical structure that critical for memory functions especially sensitive insults inflammation. We used high-resolution MR imaging at 3.0 T measure hippocampal volumes relapsing remitting MS (RRMS) secondary progressive (SPMS) patients controls. found...
Disruption of functional connectivity between brain regions may represent an early consequence β-amyloid pathology prior to clinical Alzheimer's disease. We aimed investigate if non-demented older individuals with increased amyloid burden demonstrate disruptions whole-brain in cortical hubs (brain typically highly connected multiple other areas) and these are associated neuronal dysfunction as measured fluorodeoxyglucose-positron emission tomography. In healthy subjects without cognitive...
Assessing the ability of Alzheimer disease neuroimaging markers to predict short-term cognitive decline among clinically normal (CN) individuals is critical for upcoming secondary prevention trials using outcomes.
Alzheimer's disease (AD) is characterized by two hallmark molecular pathologies: amyloid aβ1-42 and Tau neurofibrillary tangles. To date, studies of functional connectivity MRI (fcMRI) in individuals with preclinical AD have relied on associations vivo measures pathology. With the recent advent Tau-PET tracers it now possible to extend investigations fcMRI a sample cognitively normal elderly humans regional Tau. We modeled across four major cortical association networks [default-mode network...
<h3>Importance</h3> Mounting evidence suggests that sex differences exist in the pathologic trajectory of Alzheimer disease. Previous literature shows elevated levels cerebrospinal fluid tau women compared with men as a function apolipoprotein E (APOE) ε4 status and β-amyloid (Aβ). What remains unclear is association regional deposition clinically normal individuals. <h3>Objective</h3> To examine cross-sectional between Aβ measured positron emission tomography (PET). <h3>Design, Setting...
The default‐mode network (DMN) is a distributed functional‐anatomic implicated in supporting memory. Current resting‐state functional connectivity studies humans remain divided on the exact involvement of medial temporal lobe (MTL) this at rest. Notably, it unclear to what extent MTL regions involved successful memory encoding are connected cortical nodes DMN during resting state. Our findings using MRI analyses data indicate that parahippocampal gyrus (PHG) primary hub Also, PHG distinct...
To examine whether β-amyloid (Aβ) and APOE ε4 status independently contribute or interact to influence longitudinal cognitive decline in clinically normal older individuals (CN).Data from 490 CNs were aggregated across 3 observational cohort studies (Harvard Aging Brain Study, Alzheimer's Disease Neuroimaging Initiative, Australian Imaging Biomarkers Lifestyle Study of Ageing; median age = 75.0 years, 255 female), the contributions Aβ on change over a 1.49 years examined. Cognitive was...
Previous postmortem studies have long demonstrated that neurofibrillary tangles made of hyperphosphorylated tau proteins are closely associated with Alzheimer disease clinical phenotype and neurodegeneration pattern. Validating these associations in vivo will lead to new diagnostic tools for better understanding its neurobiology.
Objectives Amyloid‐beta (Aβ) and tau pathologies are commonly observed among clinically normal older individuals at postmortem can now be detected with in vivo neuroimaging. The association interaction of these proteinopathies prospective cognitive decline aging preclinical Alzheimer's disease (AD) remains to fully elucidated. Methods One hundred thirty‐seven (age = 76.3 ± 6.22 years) participating the Harvard Aging Brain Study underwent Aβ ( 11 C‐Pittsburgh compound B) 18 F‐flortaucipir)...
Cross-sectional functional magnetic resonance imaging studies using a memory task in patients with mild cognitive impairment have produced discordant results, some reporting increased hippocampal activity—consistent findings genetic at-risk populations—and other decreased activity, relative to normal controls. However, previous not included markers of amyloid-β, which may be particularly important prediction progression along the Alzheimer's disease continuum. Here, we examine contribution...
The causes of cognitive impairment in dementia with Lewy bodies (DLB) and Parkinson disease (PD) are multifactorial. Tau pathologic changes commonly observed at autopsy individuals DLB PD dementia, but their contribution to these diseases during life is unknown.
Abstract Introduction Our objective was to investigate the effect of sex on cognitive decline within context amyloid β (Aβ) burden and apolipoprotein E genotype. Methods We analyzed sex‐specific effects Aβ‐positron emission tomography, apolipoprotein, rates change Preclinical Alzheimer Cognitive Composite‐5 across three cohorts, such as Alzheimer's Disease Neuroimaging Initiative, Australian Imaging, Biomarker Lifestyle, Harvard Aging Brain Study (n = 755; clinical dementia rating 0; age...
Identifying asymptomatic individuals at high risk of impending cognitive decline because Alzheimer disease is crucial for successful prevention dementia. Vascular and β-amyloid (Aβ) pathology commonly co-occur in older adults are significant causes impairment.To determine whether vascular Aβ burden act additively or synergistically to promote clinically normal adults; and, secondarily, evaluate the unique influence on prospective beyond that used imaging biomarkers, including burden,...
We provide a comparative <i>in vivo</i> examination of the brain network-based distribution two hallmarks Alzheimer9s disease (AD) pathology in cognitively normal individuals: (1) <i>Tau</i>, detected with novel positron emission tomography (PET) tracer known as <sup>18</sup>F-AV-1451; and (2) amyloid-β, quantified <sup>11</sup>C-PiB PET. used high-resolution graph-based approach to investigate local-to-local local-to-distributed cortical associations between maps gray matter intensity. Our...
It is critically important to improve our ability diagnose and track Alzheimer disease (AD) as early possible. Individuals with autosomal dominant forms of AD can provide clues which when biological changes are reliably present prior the onset clinical symptoms.To characterize associations between amyloid tau deposits in brains cognitively unimpaired impaired carriers presenilin 1 (PSEN1) E280A mutation.In this cross-sectional imaging study, we leveraged data from a homogeneous kindred,...
Advances in molecular positron emission tomography (PET) have enabled anatomic tracking of brain pathology longitudinal studies normal aging and dementia, including assessment the central model Alzheimer's disease (AD) pathogenesis, according to which TAU begins focally but expands catastrophically under influence amyloid-β (Aβ) mediate neurodegeneration cognitive decline. Initial deposition occurs many years before Aβ a specific area medial temporal lobe. Building on recent work that focus...
Abstract We characterized the world’s second case with ascertained extreme resilience to autosomal dominant Alzheimer’s disease (ADAD). Side-by-side comparisons of this male and previously reported female ADAD homozygote for APOE3 Christchurch ( APOECh ) variant allowed us discern common features. The remained cognitively intact until 67 years age despite carrying a PSEN1 -E280A mutation. Like carrier, he had extremely elevated amyloid plaque burden limited entorhinal Tau tangle burden. He...
Postmenopausal females represent around 70% of all individuals with Alzheimer disease. Previous literature shows elevated levels tau in cognitively unimpaired postmenopausal compared age-matched males, particularly the setting high β-amyloid (Aβ). The biological mechanisms associated higher deposition female remain elusive.
To investigate default mode network (DMN) functional connectivity MRI (fcMRI) in a large cross-sectional cohort of subjects from families harboring pathogenic presenilin-1 (PSEN1), presenilin-2 (PSEN2), and amyloid precursor protein (APP) mutations participating the Dominantly Inherited Alzheimer Network.Eighty-three mutation carriers 37 asymptomatic noncarriers same underwent fMRI during resting state at 8 centers United States, Kingdom, Australia. Using group-independent component...
Age-related alterations in brain structure and function have been challenging to link cognition due potential overlapping influences of multiple neurobiological cascades. We examined markers associated with age-related variation cognition. Clinically normal older humans aged 65–90 from the Harvard Aging Brain Study (N = 186) were characterized on a priori magnetic resonance imaging gray matter thickness volume, white hyperintensities, fractional anisotropy (FA), resting-state functional...