Cerebrospinal fluid Aβ42 is the best predictor of clinical progression in patients with subjective complaints

Alzheimer's & Dementia - Tập 9 - Trang 481-487 - 2013
Argonde C. van Harten1,2, Pieter Jelle Visser1,2,3, Yolande A.L. Pijnenburg1,2, Charlotte E. Teunissen4, Marinus A. Blankenstein4, Philip Scheltens1,2, Wiesje M. van der Flier1,2,5
1Alzheimer Center, VU University Medical Center, Amsterdam, the Netherlands
2Department of Neurology, VU University Medical Center, Amsterdam, The Netherlands
3Department of Psychiatry and Neuropsychology/Alzheimer Center Limburg, School for Mental Health and Neurosciences, Maastricht University Medical Center, Maastricht, The Netherlands
4Department of Clinical Chemistry, VU University Medical Center, Amsterdam, The Netherlands
5Department of Epidemiology & Biostatistics, VU University Medical Center, Amsterdam, The Netherlands

Tóm tắt

AbstractBackgroundThe 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.MethodsWe 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.ResultsWe 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.ConclusionLow 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.

Tài liệu tham khảo

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Alzheimer's & Dementia

Tập 9

481-487

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