title: Injury markers but not amyloid markers are associated with rapid progression from mild cognitive impairment to dementia in Alzheimer's disease.
abstract: Alzheimer's disease (AD) is a common cause of mild cognitive impairment (MCI). However, the time between the diagnosis of MCI and the diagnosis of dementia is highly variable. In this study we investigated which known risk factors and biomarkers of AD pathology were associated with rapid progression from MCI to dementia. Of the 203 subjects with MCI, 91 progressed to AD-type dementia and were considered to have MCI-AD at baseline. Subjects with MCI-AD were older, more frequently female and carrier of the APOE-ε4 allele, had lower scores on the Mini-Mental State Examination (MMSE), more medial temporal lobe atrophy (MTA) and lower levels of Aβ1-42 and increased levels of t-tau and p-tau in the cerebrospinal fluid (CSF) compared to subjects without AD-type dementia at follow up. Of the 91 subjects with MCI-AD, we had data available of CSF (n = 56), MTA (n = 76), and APOE-genotype (n = 63). Among the subjects with MCI-AD, MTA (hazard ratio (HR) 2.2, p = 0.004) and low MMSE score (HR 2.0 p = 0.007) were associated with rapid progression to dementia. High CSF t-tau (HR 1.7, p = 0.07) and p-tau (1.7, p = 0.08) tended to be associated with rapid progression to dementia. CSF Aβ1-42, APOE status, age, gender, and educational level were not associated with time to dementia. Our findings implicate a different role for biomarkers in diagnosis and prognosis of MCI-AD. While amyloid markers can be used to identify MCI-AD, injury markers may predict rapid progression to dementia.
authors.affiliation: Department of Neurology/Alzheimer Center, VU Medical Center, Amsterdam, The Netherlands. i.vanrossum@vumc.nl
authors.forename: Ineke A
authors.initials: IA
authors.lastname: van Rossum
authors.forename: Pieter Jelle
authors.initials: PJ
authors.lastname: Visser
authors.forename: Dirk L
authors.initials: DL
authors.lastname: Knol
authors.forename: Wiesje M
authors.initials: WM
authors.lastname: van der Flier
authors.forename: Charlotte E
authors.initials: CE
authors.lastname: Teunissen
authors.forename: Frederik
authors.initials: F
authors.lastname: Barkhof
authors.forename: Marinus A
authors.initials: MA
authors.lastname: Blankenstein
authors.forename: Philip
authors.initials: P
authors.lastname: Scheltens
mesh_terms: D000368:Aged; D000544:Alzheimer Disease / Q000150:complications* / Q000235:genetics; D016229:Amyloid beta-Peptides / Q000378:metabolism; D053327:Apolipoprotein E4 / Q000235:genetics; D015415:Biomarkers / Q000378:metabolism*; D016009:Chi-Square Distribution; D060825:Cognitive Dysfunction / Q000150:complications* / Q000209:etiology*; D003704:Dementia / Q000175:diagnosis* / Q000209:etiology*; D018450:Disease Progression; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008137:Longitudinal Studies; D008279:Magnetic Resonance Imaging; D008297:Male; D008609:Mental Status Schedule; D008875:Middle Aged; D010446:Peptide Fragments / Q000378:metabolism; D011237:Predictive Value of Tests; D012307:Risk Factors; D012737:Sex Factors; D013702:Temporal Lobe / Q000473:pathology; D013997:Time Factors; D016875:tau Proteins / Q000134:cerebrospinal fluid
chemical_list: D016229:Amyloid beta-Peptides; D053327:Apolipoprotein E4; D015415:Biomarkers; D010446:Peptide Fragments; C075222:amyloid beta-protein (1-42); D016875:tau Proteins