Person:
Chhatwal, Jasmeer

Profile Picture

Email Address

AA Acceptance Date

Birth Date

Research Projects

Organizational Units

Job Title

Last Name

Chhatwal

First Name

Jasmeer

Name

Chhatwal, Jasmeer
Author's Publications: search.filters.isAuthorOfPublication.6e417a59-80e6-4e6b-844f-a02f13e8917c

Search Results

Now showing 1 - 2 of 2
  • Thumbnail Image
    Publication
    White matter hyperintensities and the mediating role of cerebral amyloid angiopathy in dominantly-inherited Alzheimer’s disease
    (Public Library of Science, 2018) Lee, Seonjoo; Zimmerman, Molly E.; Narkhede, Atul; Nasrabady, Sara E.; Tosto, Giuseppe; Meier, Irene B.; Benzinger, Tammie L. S.; Marcus, Daniel S.; Fagan, Anne M.; Fox, Nick C.; Cairns, Nigel J.; Holtzman, David M.; Buckles, Virginia; Ghetti, Bernardino; McDade, Eric; Martins, Ralph N.; Saykin, Andrew J.; Masters, Colin L.; Ringman, John M.; Fӧrster, Stefan; Schofield, Peter R.; Sperling, Reisa; Johnson, Keith; Chhatwal, Jasmeer; Salloway, Stephen; Correia, Stephen; Jack, Clifford R.; Weiner, Michael; Bateman, Randall J.; Morris, John C.; Mayeux, Richard; Brickman, Adam M.
    Introduction: White matter hyperintensity (WMH) volume on MRI is increased among presymptomatic individuals with autosomal dominant mutations for Alzheimer’s disease (AD). One potential explanation is that WMH, conventionally considered a marker of cerebrovascular disease, are a reflection of cerebral amyloid angiopathy (CAA) and that increased WMH in this population is a manifestation of this vascular form of primary AD pathology. We examined whether the presence of cerebral microbleeds, a marker of CAA, mediates the relationship between WMH and estimated symptom onset in individuals with and without autosomal dominant mutations for AD. Participants and methods Participants (n = 175, mean age = 41.1 years) included 112 with an AD mutation and 63 first-degree non-carrier controls. We calculated the estimated years from expected symptom onset (EYO) and analyzed baseline MRI data for WMH volume and presence of cerebral microbleeds. Mixed effects regression and tests of mediation were used to examine microbleed and WMH differences between carriers and non-carriers and to test the whether the association between WMH and mutation status is dependent on the presence of microbleeds. Results: Mutation carriers were more likely to have microbleeds than non-carriers (p<0.05) and individuals with microbleeds had higher WMH volume than those without (p<0.05). Total WMH volume was increased in mutation carriers compared with non-carriers, up to 20 years prior to EYO, after controlling for microbleed status, as we demonstrated previously. Formal testing of mediation demonstrated that 21% of the association between mutation status and WMH was mediated by presence of microbleeds (p = 0.03) but a significant direct effect of WMH remained (p = 0.02) after controlling for presence of microbleeds. Discussion Although there is some co-dependency between WMH and microbleeds, the observed increases in WMH among mutation carriers does not appear to be fully mediated by this marker of CAA. The findings highlight the possibility that WMH represent a core feature of AD independent of vascular forms of beta amyloid.
  • No Thumbnail Available
    Publication
    Degradation of Mnemonic Networks in Aging and Alzheimer’s Disease
    (2015-05-20) Chhatwal, Jasmeer; Sperling, Reisa A.; Hyman, Bradley; Dougherty, Darin; Van Dijk, Koene
    Functional connectivity MRI (fcMRI) is a non-invasive method to assess the integrity of anatomically distributed neural networks underlying complex behaviors. In Alzheimer’s disease (AD), fcMRI of the default mode network (DMN) has shown great promise as a biomarker in clinical and basic research studies, as (1) profound decreases in DMN fcMRI are seen in prodromal and clinically evident AD and (2) the DMN is among the sites of early amyloid deposition in AD. However, using fcMRI as an early AD biomarker is limited by the overlapping changes in connectivity seen in normal aging, which, in turn, limits the identification of early AD subjects to enroll in clinical trials. To address this limitation, we propose a series of studies that use fcMRI to disambiguate normal aging from early AD by focusing on the pattern of degeneration across six well-described cortical networks in two unique subject populations. The central hypothesis of these studies is that early AD and aging will show distinct patterns of network degradation, with preferential degradation of cognitive networks (especially the Default Mode and Attention Networks) in early AD as compared to aging. We test this hypothesis by comparing young and old subjects with and without evidence of AD pathology, leveraging newly available data from young subjects with dominantly inherited AD (DIAD) drawn from the Dominantly-Inherited Alzheimer’s Network (DIAN). Notably, the comparison of the DIAD population and older at-risk and symptomatic patients followed in the Harvard Aging Brain Study represents a unique opportunity to disentangle age and AD pathology, as DIAD carriers have disease onset at a young age (often in the late 30s and early 40s). In addition, using PET data on tau burden in our older subjects (from F18-T807 PET, a newly-developed tau radioligand), we will explore the relative contributions of amyloid and tau pathologies to altered fcMRI. These studies will serve the dual purpose of (1) optimizing the use of fcMRI as an AD biomarker by identifying patterns of fcMRI change that distinguish aging and AD, and (2) provide novel insight into the systems-level pathophysiology that distinguishes aging and AD. Further, these studies will compare the timing and pattern of network degradation in dominantly-inherited vs. sporadic AD and provide critical context for the interpretation of fcMRI data currently being gathered in (at least) three major AD prevention trials in older individuals at-risk for sporadic AD and dominantly-inherited AD.