Neuropathological basis of magnetic resonance images in aging and dementia

Abstract

Objective: Magnetic resonance (MR) imaging is used widely for assessment of patients with cognitive impairment, but the pathological correlates are unclear, especially when multiple pathologies are present.

Methods: This report includes 93 subjects from a longitudinally followed cohort recruited for the study of Alzheimer's disease (AD) and subcortical cerebrovascular disease (CVD). MR images were analyzed to quantify cortical gray matter volume, hippocampal volume, white matter hyperintensities, and lacunes. Neuropathological examination quantified CVD parenchymal pathology, AD pathology (defined as Consortium to Establish a Registry for Alzheimer's Disease scores and Braak and Braak stage), and hippocampal sclerosis. Subjects were pathologically classified as 12 healthy control subjects, 46 AD, 14 CVD, 9 mixed AD/CVD, and 12 cognitively impaired patients without significant AD/CVD pathology. Multivariate models tested associations between magnetic resonance and pathological findings across the entire sample.

Results: Pathological correlates of cortical gray matter volume were AD, subcortical vascular pathology, and arteriosclerosis. Hippocampal volume was related to AD pathology and hippocampal sclerosis, and the effects of hippocampal sclerosis were greater for subjects with low levels of AD pathology. White matter hyperintensities were related to age and to white matter pathology. Number of MRI lacunes was related to subcortical vascular pathology.

Interpretation: In this clinical setting, the presence of lacunes and white matter changes provide a good signal for vascular disease. The neuropathological basis of MR defined cerebral cortical and hippocampal atrophy in aging and dementia is complex, with several pathological processes converging on similar brain structures that mediate cognitive decline.

Fig 1

Frequency histograms indicating the distribution of neuropathological abnormalities in the 93 autopsied cases. (A) Cerebrovascular disease parenchymal score, (B) Braak stage, and (C) Consortium to Establish a Registry for Alzheimer’s Disease plaque score.

Fig 2

Box plots showing the distribution of quantitative magnetic resonance imaging volumes by pathological group. Solid squares denote minimum; multiply signs denote first quartile; solid triangles denote median; open circles denote third quartile; asterisks denote maximum. AD = Alzheimer’s disease; CVD = cerebrovascular disease; NC = cognitively normal and no significant pathology; OTHER = cognitively impaired without significant pathology.

Fig 3

Relation between pathologically measured hippocampal sclerosis and magnetic resonance measured hippocampal volume for two groups of subjects defined by the extent of Alzheimer’s disease (AD) pathology using a median split. Triangles denote low AD; circles denote high AD; solid line denotes low AD; dotted line denotes high AD.