Meta-analysis of CSF and MRI biomarkers for detecting preclinical Alzheimer's disease

• Published in: Psychological medicine Vol. 40; no. 1; pp. 135 - 145
• Main Authors: Schmand, B., Huizenga, H. M., van Gool, W. A.
• Format: Journal Article
• Language: English
• Published: Cambridge, UK Cambridge University Press 01.01.2010
• Subjects: Adult and adolescent clinical studies; Alzheimer Disease - cerebrospinal fluid; Alzheimer Disease - diagnosis; Alzheimer's disease; Amyloid beta-Peptides - cerebrospinal fluid; Atrophy; beta-amyloid; Biological and medical sciences; Biological markers; Biomarkers; Biomarkers - cerebrospinal fluid; Body fluids; Brain - pathology; cerebrospinal fluid; Cognition Disorders - cerebrospinal fluid; Cognition Disorders - diagnosis; Degenerative and inherited degenerative diseases of the nervous system. Leukodystrophies. Prion diseases; Delayed memory; delayed recall; Diagnosis; Early Diagnosis; Geriatrics; hippocampus; Hippocampus - pathology; Humans; longitudinal studies; Magnetic Resonance Imaging; medial temporal lobe; Medical sciences; Memory; Meta-analysis; meta-regression; mild cognitive impairment; MRI; Neurology; Neuropsychological Tests; NMR; Nuclear magnetic resonance; Organic mental disorders. Neuropsychology; phosphorylated tau; Psychology. Psychoanalysis. Psychiatry; Psychopathology. Psychiatry; Systematic review; tau Proteins - cerebrospinal fluid; Temporal Lobe - pathology; total tau; memory; hippocampus; MRI; delayed recall; meta-analysis; meta-regression; phosphorylated tau; beta-amyloid; medial temporal lobe; total tau; cerebrospinal fluid; mild cognitive impairment; Alzheimer's disease; longitudinal studies; Phosphorylation; Cognitive disorder; Alzheimer disease; Memory; Central nervous system; Biological marker; Asymptomatic; Review; Cerebrospinal fluid; Encephalon; Metaanalysis; Medial temporal lobe; Degenerative disease; Recall; Human; Nervous system diseases; Nuclear magnetic resonance imaging; Cerebral disorder; Tau protein; Follow up study; β Amyloid protein; Central nervous system disease; Medical imagery; Hippocampus
• ISSN: 0033-2917; 1469-8978
• DOI: 10.1017/S0033291709991516

Abnormal levels of biomarkers in cerebrospinal fluid (CSF) and atrophy of medial temporal lobe (MTL) structures on magnetic resonance imaging (MRI) are being used increasingly to diagnose early Alzheimer's disease (AD). We evaluated the claim that these biomarkers can detect preclinical AD before behavioural (i.e. memory) symptoms arise. We included all relevant longitudinal studies of CSF and MRI biomarkers published between January 2003 and November 2008. Subjects were not demented at baseline but some declined to mild cognitive impairment (MCI) or to AD during follow-up. Measures of tau and beta-amyloid in CSF, MTL atrophy on MRI, and performance on delayed memory tasks were extracted from the papers or obtained from the investigators. Twenty-one MRI studies and 14 CSF studies were retrieved. The effect sizes of total tau (t-tau), phosphorylated tau (p-tau) and amyloid beta 42 (a beta 42) ranged from 0.91 to 1.11. The effect size of MTL atrophy was 0.75. Memory performance had an effect size of 1.06. MTL atrophy and memory impairment tended to increase when assessed closer to the moment of diagnosis, whereas effect sizes of CSF biomarkers tended to increase when assessed longer before the diagnosis. Memory impairment is a more accurate predictor of early AD than atrophy of MTL on MRI, whereas CSF abnormalities and memory impairment are about equally predictive. Consequently, the CSF and MRI biomarkers are not very sensitive to preclinical AD. CSF markers remain promising, but studies with long follow-up periods in elderly subjects who are normal at baseline are needed to evaluate this promise.