Injury Markers but not Amyloid Markers are Associated with Rapid Progression from Mild Cognitive Impairment to Dementia in Alzheimer's Disease

Article type: Research Article

Authors: van Rossum, Ineke A.^{a; *} | Visser, Pieter Jelle^{a; e} | Knol, Dirk L.^b | van der Flier, Wiesje M.^{a; b} | Teunissen, Charlotte E.^c | Barkhof, Frederik^d | Blankenstein, Marinus A.^c | Scheltens, Philip^e

Affiliations: [a] Department of Neurology/Alzheimer Center, VU Medical Center, Amsterdam, The Netherlands | [b] Department of Epidemiology and Biostatistics, VU Medical Center, Amsterdam, The Netherlands | [c] Department of Clinical Chemistry, VU Medical Center, Amsterdam, The Netherlands | [d] Department of Radiology, VU Medical Center, Amsterdam, The Netherlands | [e] Department of Psychiatry and Neuropsychology, Maastricht University, School for Mental Health and Neuroscience, Alzheimer Center Limburg, VU Medical Center, Amsterdam, The Netherlands

Correspondence: [*] Correspondence to: Ineke van Rossum, Alzheimer Center VU University Medical Center, P.O. Box 7057, 1007 MB Amsterdam, the Netherlands. Tel.: +31 204448527; Fax: +31 204440715; E-mail: [email protected].

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.

Keywords: Alzheimer's disease, biomarkers, cerebrospinal fluid, clinical progression, magnetic resonance imaging, mild cognitive impairment

DOI: 10.3233/JAD-2011-111694

Journal: Journal of Alzheimer's Disease, vol. 29, no. 2, pp. 319-327, 2012