title: Alzheimer's disease markers, hypertension, and gray matter damage in normal elderly.
abstract: It is not well known whether Alzheimer's disease (AD) cerebrospinal fluid (CSF) biomarkers are associated with brain damage in cognitively normal elderly. The combined influence of CSF biomarkers and hypertension (HTN) on the gray matter (GM) is also not well described. One hundred fifteen cognitively healthy subjects (mean age 62.6 ± 9.5%, 62% women) received clinical assessment, a high resolution magnetic resonance imaging (MRI), and a lumbar puncture. The CSF levels of total tau (t-tau), hyperphosphorylated tau (p-tau(231)), amyloid beta (Aβ42/Aβ40), p-tau(231)/Aβ42, and t-tau/Aβ42 were dichotomized as "high" and "low" based on accepted cut off values. Statistical parametric mapping was used to examine MRI scans for regional GM density, studied as a function of the CSF markers, HTN, and combination of both. Global and medial temporal lobe (MTL) GM was also assessed. Voxel based morphometry revealed that higher t-tau was associated with lower GM density in the precunei. Subjects with higher p-tau(231) and p-tau(231)/Aβ42 had less GM in temporal lobes. Low Aβ42/Aβ40 was related to less GM in the thalami, caudate, and midbrain. Subjects with hypertension showed more GM atrophy in the cerebellum, occipital, and frontal regions. Simultaneous presence of elevated CSF AD biomarkers and HTN was associated with more GM atrophy than either marker individually, but no interaction effects were identified. In conclusion, in normal elderly CSF tau markers were associated predominantly with lower GM estimates in structures typically affected early in the AD process. In this presymptomatic stage when no cognitive impairment is present, AD biomarkers and HTN have additive effects on gray matter damage.
authors.affiliation: Center of Excellence on Aging, Center for Brain Health, Department of Psychiatry, New York University School of Medicine, New York, NY 10016, USA. Lidia.Glodzik@nyumc.org
authors.forename: Lidia
authors.initials: L
authors.lastname: Glodzik
authors.forename: Lisa
authors.initials: L
authors.lastname: Mosconi
authors.forename: Wai
authors.initials: W
authors.lastname: Tsui
authors.forename: Susan
authors.initials: S
authors.lastname: de Santi
authors.forename: Raymond
authors.initials: R
authors.lastname: Zinkowski
authors.forename: Elizabeth
authors.initials: E
authors.lastname: Pirraglia
authors.forename: Kenneth E
authors.initials: KE
authors.lastname: Rich
authors.forename: Pauline
authors.initials: P
authors.lastname: McHugh
authors.forename: Yi
authors.initials: Y
authors.lastname: Li
authors.forename: Schantel
authors.initials: S
authors.lastname: Williams
authors.forename: Fahad
authors.initials: F
authors.lastname: Ali
authors.forename: Henrik
authors.initials: H
authors.lastname: Zetterberg
authors.forename: Kaj
authors.initials: K
authors.lastname: Blennow
authors.forename: Pankaj
authors.initials: P
authors.lastname: Mehta
authors.forename: Mony J
authors.initials: MJ
authors.lastname: de Leon
mesh_terms: D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000134:cerebrospinal fluid* / Q000473:pathology* / Q000523:psychology; D000544:Alzheimer Disease / Q000134:cerebrospinal fluid* / Q000473:pathology* / Q000523:psychology; D001284:Atrophy; D015415:Biomarkers / Q000134:cerebrospinal fluid / Q000378:metabolism; D002540:Cerebral Cortex / Q000378:metabolism / Q000473:pathology*; D003430:Cross-Sectional Studies; D005260:Female; D006801:Humans; D006973:Hypertension / Q000134:cerebrospinal fluid* / Q000473:pathology* / Q000523:psychology; D008297:Male; D008875:Middle Aged
chemical_list: D015415:Biomarkers