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F1‐03‐02: REGIONAL VARIABILITY OF IMAGING BIOMARKERS IN DIAN
Author(s) -
Benzinger Tammie,
Fagan Anne,
Chhatwal Jasmeer,
Morris John C.,
Rossor Martin,
Bateman Randall
Publication year - 2014
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.2014.04.054
Subject(s) - pittsburgh compound b , atrophy , imaging biomarker , biomarker , neuroimaging , alzheimer's disease neuroimaging initiative , pathology , striatum , medicine , nuclear medicine , magnetic resonance imaging , alzheimer's disease , neuroscience , disease , chemistry , psychology , radiology , biochemistry , dopamine
families are rare (w517 have been identified worldwide). DIAN established performance sites at selected academic medical centers in Australia, Europe, and the United States. Each site adopted the same comprehensive assessment protocol, comprised of standard instruments and procedures, for uniform administration to DIAN participants at baseline and longitudinally. The protocol assesses the clinical, cognitive, and behavioral features of ADAD and includes multimodal neuroimaging (structural MRI, rs-fcMRI, FDG-PET, PIB-PET) and biofluid (blood, cerebrospinal fluid) assays. Results: Across 14 performance sites, 371 participants (mutation carriers [MCs] and noncarriers [NCs]; asymptomatic and symptomatic) were enrolled in DIAN as of 12/31/13. The participants represent 137ADAD familieswith 76mutations (63 PSEN1, 2 PSEN2, 11 APP). Baseline completion rates of DIAN procedures exceed 90% for all components (lumbar puncture 82%); 71% of participants at baseline and 60% at follow-up complete all components. Baseline characteristics of the cohort are shown in the Table. Global cognitive deficits of symptomatic MCs are similar to those of persons with late onset AD, and deficits in episodic memory and attentional control distinguish asymptomatic MCs from NCs. Cross-sectional analysis of imaging and fluid biomarkers in the DIAN cohort supports the concept of a pathophysiological cascade in the brain that begins perhaps 20-25 years prior to symptomatic onset of ADAD. Only MCs develop biomarker changes. Conclusions: DIAN represents the largest ever cohort established from multiple ADAD kindreds. It validates biomarkers of the molecular pathology of AD to characterize a preclinical stage of AD.