title: Subgroup of ADNI normal controls characterized by atrophy and cognitive decline associated with vascular damage.
abstract: Previous work examining Alzheimer's Disease Neuroimaging Initiative (ADNI) normal controls using cluster analysis identified a subgroup characterized by substantial brain atrophy and white matter hyperintensities (WMH). We hypothesized that these effects could be related to vascular damage. Fifty-three individuals in the suspected vascular cluster (Normal 2) were compared with 31 individuals from the cluster characterized as healthy/typical (Normal 1) on a variety of outcomes, including magnetic resonance imaging (MRI) and cerebrospinal fluid (CSF) biomarkers, vascular risk factors and outcomes, cognitive trajectory, and medications for vascular conditions. Normal 2 was significantly older but did not differ on ApoE4+ prevalence. Normal 2 differed significantly from Normal 1 on all MRI measures but not on Amyloid-Beta1-42 or total tau protein. Normal 2 had significantly higher body mass index (BMI), Hachinksi score, and creatinine levels, and took significantly more medications for vascular conditions. Normal 2 had marginally significantly higher triglycerides and blood glucose. Normal 2 had a worse cognitive trajectory on the Rey's Auditory Verbal Learning Test (RAVLT) 30-min delay test and the Functional Activity Questionnaire (FAQ). Cerebral atrophy associated with multiple vascular risks is common among cognitively normal individuals, forming a distinct subgroup with significantly increased cognitive decline. Further studies are needed to determine the clinical impact of these findings.
authors.affiliation: Clinical and Translational Science Center, University of California, Davis, School of Medicine, Sacramento, CA 95817, USA. janettik@ucdavis.edu
authors.forename: Jasmine
authors.initials: J
authors.lastname: Nettiksimmons
authors.forename: Laurel
authors.initials: L
authors.lastname: Beckett
authors.forename: Christopher
authors.initials: C
authors.lastname: Schwarz
authors.forename: Owen
authors.initials: O
authors.lastname: Carmichael
authors.forename: Evan
authors.initials: E
authors.lastname: Fletcher
authors.forename: Charles
authors.initials: C
authors.lastname: Decarli
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000473:pathology* / Q000502:physiology; D000544:Alzheimer Disease / Q000097:blood / Q000134:cerebrospinal fluid / Q000473:pathology; D001284:Atrophy; D015415:Biomarkers / Q000097:blood / Q000134:cerebrospinal fluid / Q000378:metabolism; D001921:Brain / Q000473:pathology* / Q000503:physiopathology; D002561:Cerebrovascular Disorders / Q000150:complications / Q000473:pathology* / Q000503:physiopathology; D003072:Cognition Disorders / Q000209:etiology / Q000473:pathology* / Q000503:physiopathology; D005260:Female; D006801:Humans; D008297:Male; D012042:Registries
chemical_list: D015415:Biomarkers