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IC‐P‐051: Amyloid load increase and cerebral microbleed prevalence differ as a function of the position of the mutation within the PSEN1 coding sequence
Author(s) -
Joseph-Mathurin Nelly,
Tang Mengxuan,
Friedrichsen Karl A.,
Owen Christopher J.,
Su Yi,
Hornbeck Russ C.,
Stevenson Trish A.,
Cash Lisa,
Raichle Marcus E.,
Gordon Brian,
Preboske Gregory M.,
Koeppe Robert A.,
Jack Clifford R.,
Goate Alison,
Cruchaga Carlos,
Xiong Chengjie,
Moulder Krista L.,
Buckles Virginia,
Bateman Randall,
Morris John C.,
Benzinger Tammie L.S.
Publication year - 2015
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1016/j.jalz.2015.06.072
Subject(s) - psen1 , mutation , amyloidosis , cerebral amyloid angiopathy , amyloid (mycology) , magnetic resonance imaging , population , medicine , pittsburgh compound b , standardized uptake value , coding region , pathology , dementia , amyloid precursor protein , genetics , nuclear medicine , alzheimer's disease , biology , positron emission tomography , gene , disease , radiology , environmental health
modifying agents, sensitive biomarkers of early FTD are crucial. Previous cross-sectional studies already demonstrated imaging abnormalities in presymptomatic FTD. Our present study investigates longitudinal neuropsychological and imaging alterations in presymptomatic FTD. Methods: Healthy MAPT or GRN mutation carriers (n1⁄440) and related non-carriers (n1⁄437) underwent neuropsychological assessment and MRI at baseline and two-years follow-up. Grey matter volume, white matter integrity, and functional connectivity were analyzed over time using voxel-based morphometry, tract-based spatial statistics, and seed-based analyses. To investigate group differences in association with expected onset age, and to explore individual data, grey matter volumes were extracted for the insula and anterior and posterior cingulate cortex and FA values were extracted for the uncinate fasciculus, and forceps minor and major. Results: Longitudinal analyses revealed a significant decline in executive and social cognition tasks, stronger right insular atrophy, and stronger white matter impairment in the uncinate fasciculus over a two-year period in carriers within five before estimated symptom onset compared to controls. Two mutation carriers converted to clinical FTD during follow-up. Interestingly, they already showed the worst DTI values at baseline (Figure 1B) as well as the strongest grey matter atrophy over time (Figure 1A). The total group of mutation carriers differed from controls regarding longitudinal alterations in frontoinsula and posterior cingulate functional connectivity that cannot be driven by the two converters, as their values cannot be distinguished from those of other subjects at baseline, follow-up or longitudinally (Figure 1C). Conclusions: We demonstrated longitudinal changes in neuropsychological performance, greymatter volume, white matter integrity, and functional connectivity in presymptomatic FTD. This study suggests that DTI might provide a baseline predictor for disease conversion, and that the first DTI changes might reflect the optimal starting point for a disease-modifying intervention. Moreover, grey matter volume and white matter integrity could serve as sensitive biomarkers in future therapeutic trials at the individual level.