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

Abstract

Objectives-i) to assess the diagnostic specificity of MRI-defined hippocampal atrophy for Alzheimer's disease (AD) among individuals with a variety of pathologically confirmed conditions associated with dementia as well as changes attributable to typical aging, and, ii) to measure correlations among pre-mortem MRI measurements of hippocampal atrophy, mental status exam performance, and the pathologic stage of AD. Methods-An un-selected series of 67 individuals participating in the Mayo Alzheimer's DiseaseResearch Center/Alzheimer's Disease Patient Registry were identified who had undergone a standardized antemortem MRI study and also post-mortem examination. Hippocampal volumes were measured from antemortem MRI. Each post-mortem specimen was assigned a pathologic diagnosis, and in addition, the severity of AD pathology was staged using the method of Braak and Braak.Results-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 p<0.001) were observed between hippocampal volume and Braak stage (r = −0.39), between hippocampal volume and MMSE score (r = 0.60), and between MMSE score and Braak stage (r = −0.41).Conclusions-Hippocampal atrophy, while not specific for AD, was a fairly sensitive marker of the pathologic AD stage [particularly among subjects with isolated AD pathology (r = −0.63, p = 0.001)] and consequent cognitive status.

Quantitative magnetic resonance techniques as surrogate markers of Alzheimer’s disease

“…Few studies have correlated quantitative MR measurements with the histopathologic diagnosis and staging so far. The correlation between antemortem MR measurements of the hippocampal volumes and postmortem Braak and Braak staging 3 indicate that hippocampal atrophy, although not specific for AD, is a fairly sensitive marker of pathologic stage 80 and hippocampal neurofibrillary tangle burden. 81 MR-based hippocampal volume measurements on postmortem samples further show a strong correlation between hippocampal volumes and neuron numbers, validating the sensitivity of the technique to hippocampal neurodegeneration.…”

“…MR-based volumetry is a sensitive marker for the pathologic progression of AD. 80 Two studies showed that MR-based volumetry techniques in AD may have enough power to measure the rate of structural change in the brain in a clinical trial setting if the magnitude of treatment effect is Ͼ10%. 89,97 The feasibility of MR-based volumetry as a treatment outcome measure in AD was tested in a multisite therapeutic trial of milameline, a centrally active muscarinic agonist.…”

Ways toward an early diagnosis in Alzheimer's disease: The Alzheimer's Disease Neuroimaging Initiative (ADNI)

“…In contrast, CT has the advantage of shorter acquisition times, ie, it is less prone to motion artifacts, and its use is not restricted by metal implants or claustrophobia. Several studies have found a good correlation between degree of atrophy on structural imaging and histopathologically confirmed neuron loss and AD pathology [26,34,35] and between progression of cognitive impairment and atrophy rate [31,36]. Mirroring the progression of the tangle pathology, atrophic changes detected by structural imaging affect primarily the entorhinal cortex and hippocampus in the stage of MCI, progress to temporal and parietal lobes in AD, and finally involve the frontal lobes in late stages of AD [26,31,[37][38][39].…”

Feasibility of Multi-site Clinical Structural Neuroimaging Studies of Aging Using Legacy Data

“…We focus on hippocampal volume as our primary measure of interest given its role in normal aging, mild cognitive impairment (MCI), and AD. Hippocampal volume has been shown to decline with normal aging (Mu et al 1999;Jernigan et al 2001a;Allen et al 2005;Walhovd et al 2005;van de Pol et al 2006) and in AD (Jack et al 2002;van de Pol et al 2006), and this region has been an intense area of study in the search for an in vivo biomarker in individuals at risk for AD (Csernansky et al 2005;Jack et al 2005). Such a biomarker could be used in the diagnosis of AD and as a marker of effectiveness in therapeutic trials Kantarci and Jack 2003).…”