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Cerebrospinal fluid Aβ42 is the best predictor of clinical progression in patients with subjective complaints
Author(s) -
Harten Argonde C.,
Visser Pieter Jelle,
Pijnenburg Yolande A.L.,
Teunissen Charlotte E.,
Blankenstein Marinus A.,
Scheltens Philip,
Flier Wiesje M.
Publication year - 2013
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.2012.08.004
Subject(s) - medicine , hazard ratio , cerebrospinal fluid , predictive value , memory clinic , proportional hazards model , cognitive impairment , oncology , disease , confidence interval
Background The need to recognize Alzheimer's disease (AD) as early as possible led us to evaluate the predictive value of amyloid β(1‐42) (Aβ42), total tau (tau), and phosphorylated tau (ptau) in cerebrospinal fluid (CSF) for clinical progression in patients with subjective complaints. Methods We recruited nondemented patients with subjective complaints (i.e., criteria for mild cognitive impairment [MCI] not fulfilled) from our memory clinic. We assessed the predictive value of CSF Aβ42, tau, and ptau for clinical progression using Cox proportional hazards models adjusted for age, gender, and baseline findings on the Mini‐Mental State Examination (MMSE). Clinical progression was defined as progression to MCI or AD. Results We included 127 patients with subjective complaints (age 60 ± 10 years, 61 [48%] females, MMSE 29 ± 1). At baseline, Aβ42 and tau were abnormal in 20 patients (both 16%), and ptau in 32 patients (25%). Thirteen patients (10%) progressed to MCI (n = 11) or AD (n = 2). Aβ42 was the strongest predictor of progression to MCI or AD with an adjusted hazard ratio (HR) of 16.0 (3.8–66.4). The adjusted HR associated with tau was 2.8 (0.9–9.2) and with ptau 2.6 (0.8–8.2). Combinations of biomarkers had a lower predictive value than Aβ42 alone. Conclusion Low Aβ42 was the strongest predictor of clinical progression in patients with subjective complaints. These results are in line with the hypothesis that the cascade of pathologic events starts with deposition of Aβ42, whereas neuronal degeneration and hyperphosphorylation of tau are more downstream events, closer to clinical manifestation of AD.