Myelin content changes in probable Alzheimer's disease and mild cognitive impairment: Associations with age and severity of neuropsychiatric impairment

Abstract

Background: Existing indices of white matter integrity such as fractional anisotropy and magnetization transfer ratio may not provide optimal specificity to myelin content. In contrast, myelin water fraction (MWF) derived from the multiecho T₂ relaxation time technique may serve as a more direct measure of myelin content.

Purpose/hypothesis: The goal of the present study was to identify markers of regional demyelination in patients with probable Alzheimer's disease (AD) and mild cognitive impairment (MCI) in relation to age and severity of neuropsychiatric impairment.

Population: The sample included patients diagnosed with probable AD (n = 25) or MCI (n = 43), and cognitively intact elderly controls (n = 33).

Field strength/sequence assessment: Long T₂ , short T₂ , and MWF values were measured with a 1.5T scanner in periventricular and deep normal-appearing white matter (NAWM), serving as indices of intra/extracellular water content and myelin content. A comprehensive neuropsychological and neuropsychiatric assessment was administered to all participants.

Statistical tests, results: AD patients displayed higher age-adjusted long and short T₂ values and reduced MWF values in left temporal/parietal and bilateral periventricular NAWM than controls and MCI patients (P < 0.004; one-way analysis of covariance [ANCOVA] tests). Short T₂ /MWF values in temporal, frontal, and periventricular NAWM of controls and/or MCI patients were significantly associated with episodic and semantic memory performance and depressive symptomatology (P < 0.004; partial correlation indices). The impact of age on memory performance was significantly (P < 0.01; mediated linear regression analyses) mediated by age-related changes in short T₂ and MWF values in these regions.

Data conclusion: Age-related demyelination is associated with memory impairment (especially in prodromal dementia states) and symptoms of depression in an anatomically specific manner.

Level of evidence: 1 Technical Efficacy: Stage 3 J. Magn. Reson. Imaging 2018;47:1359-1372.

Keywords: Alzheimer's disease; T2 relaxometry; depression; magnetic resonance imaging (MRI); memory; mild cognitive impairment.