Antemortem MRI findings correlate with hippocampal neuropathology in typical aging and dementia

TLDR

The study aimed to determine how well MRI‑defined hippocampal atrophy distinguishes Alzheimer’s disease from other dementia causes and aging, and to examine its correlation with cognitive scores and postmortem AD pathology. Researchers analyzed 67 Mayo Clinic participants who underwent standardized antemortem MRI, measured hippocampal volumes, and had postmortem diagnoses and Braak staging. Hippocampal atrophy was common in isolated AD, hippocampal sclerosis, frontotemporal degeneration, and tangle‑only disease but absent in typical aging, and it correlated inversely with Braak stage (r = −0.39), positively with MMSE (r = 0.60), and MMSE inversely with Braak stage (r = −0.41), indicating that while not specific, atrophy sensitively reflects AD severity and cognitive decline.

Abstract

<b><i>Objectives:</i></b> To assess the diagnostic specificity of MRI-defined hippocampal atrophy for AD among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and to measure correlations among premortem MRI measurements of hippocampal atrophy, mental status examination performance, and the pathologic stage of AD. <b><i>Methods:</i></b> An unselected series of 67 individuals participating in the Mayo Alzheimer’s Disease Research Center/Alzheimer’s Disease Patient Registry who had undergone a standardized antemortem MRI study and also postmortem examination were identified. Hippocampal volumes were measured from antemortem MRI. Each postmortem specimen was assigned a pathologic diagnosis and in addition, the severity of AD pathology was staged using the method of Braak and Braak. <b><i>Results:</i></b> Individuals with an isolated pathologic diagnosis of AD, hippocampal sclerosis, frontotemporal degeneration, and neurofibrillary tangle–only degeneration usually had substantial hippocampal atrophy, while those with changes of typical aging did not. Among all 67 subjects, correlations (all <i>p</i> &lt; 0.001) were observed between hippocampal volume and Braak and Braak stage (<i>r</i> = −0.39), between hippocampal volume and Mini-Mental State Examination (MMSE) score (<i>r</i> = 0.60), and between MMSE score and Braak and Braak stage (<i>r</i> = −0.41). <b><i>Conclusions:</i></b> Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage (particularly among subjects with isolated AD pathology [<i>r</i> = −0.63, <i>p</i> = 0.001]) and consequent cognitive status.