ABSTRACT
BACKGROUND: The cerebrospinal fluid (CSF) biomarkers amyloid-ß 1-42 (Aß42), total and phosphorylated tau (t-tau, p-tau) are increasingly used to assist in the clinical diagnosis of Alzheimer's disease (AD). However, CSF biomarker levels can be affected by confounding factors. OBJECTIVE: To investigate the association of white matter hyperintensities (WMHs) present in the brain with AD CSF biomarker levels. METHODS: We included CSF biomarker and magnetic resonance imaging (MRI) data of 172 subjects (52 controls, 72 mild cognitive impairment (MCI), and 48 AD patients) from 9 European Memory Clinics. A computer aided detection system for standardized automated segmentation of WMHs was used on MRI scans to determine WMH volumes. Association of WMH volume with AD CSF biomarkers was determined using linear regression analysis. RESULTS: A small, negative association of CSF Aß42, but not p-tau and t-tau, levels with WMH volume was observed in the AD (r2â=â0.084, pâ=â0.046), but not the MCI and control groups, which was slightly increased when including the distance of WMHs to the ventricles in the analysis (r2â=â0.105, pâ=â0.025). Three global patterns of WMH distribution, either with 1) a low, 2) a peak close to the ventricles, or 3) a high, broadly-distributed WMH volume could be observed in brains of subjects in each diagnostic group. CONCLUSION: Despite an association of WMH volume with CSF Aß42 levels in AD patients, the occurrence of WMHs is not accompanied by excess release of cellular proteins in the CSF, suggesting that WMHs are no major confounder for AD CSF biomarker assessment.
Subject(s)
Alzheimer Disease/cerebrospinal fluid , Amyloid beta-Peptides/cerebrospinal fluid , Cognitive Dysfunction/cerebrospinal fluid , Leukoencephalopathies/cerebrospinal fluid , Peptide Fragments/cerebrospinal fluid , tau Proteins/cerebrospinal fluid , Aged , Alzheimer Disease/diagnosis , Cognitive Dysfunction/diagnosis , Confounding Factors, Epidemiologic , Female , Humans , Image Processing, Computer-Assisted , Leukoencephalopathies/diagnostic imaging , Magnetic Resonance Imaging , Male , Middle Aged , PhosphorylationABSTRACT
Elderly patients may present with prominent cognitive complaints and have performances in neuropsychological tests within the normal range for the age and education, and thus do not fulfill the criteria for mild cognitive impairment (MCI). There is insufficient evidence to support the clinical decision in these cases ("pre-MCI"). Forty-three subjects, 11 controls, 15 "pre-MCI," and 17 MCI, were followed for about three and half years with neuropsychological testing and magnetic resonance imaging including volumetric measurements of the hippocampus and amygdala. Two of the "pre-MCI" subjects suffered cognitive and functional deterioration and were diagnosed with dementia. Although the "pre-MCI" subjects as a group had no significant deterioration in neuropsychological tests, they suffered a decline in the total hippocampal volume (P=0.04) along the follow-up time. In contrast, all control subjects remained stable and had no volumetric decreases. As expected, MCI patients underwent significant deterioration in several neuropsychological tests, often progressed to Alzheimer's disease, and showed decreases both in total hippocampal and amygdalar volumes. Elderly people presenting with cognitive complaints may be in an initial phase of a degenerative disorder and should be followed clinically, even if they have normal neuropsychological tests.
