Medial temporal lobe atrophy on MRI differentiates Alzheimer's disease from dementia with Lewy bodies and vascular cognitive impairment: a prospective study with pathological verification of diagnosis

Abstract

The purpose of this study was to determine the diagnostic accuracy of medial temporal lobe atrophy (MTA) on MRI for distinguishing Alzheimer's disease from other dementias in autopsy confirmed cases, and to determine pathological correlates of MTA in Alzheimer's disease, dementia with Lewy bodies (DLB) and vascular cognitive impairment (VCI). We studied 46 individuals who had both antemortem MRI and an autopsy. Subjects were clinicopathologically classified as having Alzheimer's disease (n = 11), DLB (n = 23) or VCI (n = 12). MTA was rated visually using a standardized (Scheltens) scale blind to clinical or autopsy diagnosis. Neuropathological analysis included Braak staging as well as quantitative analysis of plaques, tangles and alpha-synuclein Lewy body-associated pathology in the hippocampus. Correlations between MTA and pathological measures were carried out using Spearman's rho, linear regression to assess the contributions of local pathologic changes to MTA. Receiver operator curve analysis was used to assess the diagnostic specificity of MTA for Alzheimer's disease among individuals with Alzheimer's disease, DLB and VCI. MTA was a highly accurate diagnostic marker for autopsy confirmed Alzheimer's disease (sensitivity of 91% and specificity of 94%) compared with DLB and VCI. Across the entire sample, correlations were observed between MTA and Braak stage (rho = 0.50, P < 0.001), per cent area of plaques in the hippocampus (rho = 0.37, P = 0.014) and per cent area of tangles in the hippocampus (rho = 0.49, P = 0.001). Linear regression showed Braak stage (P = 0.022) to be a significant predictor of MTA but not percent area of plaques (P = 0.375), percent area of tangles (P = 0.330) or percent area of Lewy bodies (P = 0.086). MTA on MRI had robust discriminatory power for distinguishing Alzheimer's disease from DLB and VCI in pathologically confirmed cases. Pathologically, it is more strongly related to tangle rather than plaque or Lewy body pathology in the temporal lobe. It may have utility as a means for stratifying samples in vivo on the basis of putative differences in pathology.

Alzheimer’s Diseases: Towards Biomarkers for an Early Diagnosis

“…Effectively, this cerebral structure highly participates in the memory process; even more, neuropathological findings demonstrated the strong implication of typical protein depositions met in AD that occur during this medial temporal lobe atrophy (Burton, Barber et al 2009). Nevertheless, this kind of atrophy can be met in other pathologies such as FTLD or DLB, without any cerebral pathological hallmark of AD (O'Brien, Paling et al 2001;van de Pol, Hensel et al 2006).…”

Amyloid-β deposition and regional grey matter atrophy rates in dementia with Lewy bodies

“…Atrophy in the limbic, temporal and parietal association cortices on structural MRI is a marker of neurodegeneration associated with tau neurofibrillary tangle pathology of Alzheimer's disease and DLB (Jack et al, 2004;Burton et al, 2009;Murray et al, 2013). In several studies, patients with probable DLB showed an Alzheimer's diseaselike pattern of atrophy (Whitwell et al, 2007b;Sabattoli et al, 2008;Zhong et al, 2014) while autopsy confirmation later showed that the presence of tau neurofibrillary tangles and their Braak stage (Braak and Braak, 1991) of Alzheimer's disease primarily explained the cross-sectional (Burton et al, 2009;Kantarci et al, 2012a;Murray et al, 2013) and longitudinal (Nedelska et al, 2015) atrophy observed in the medial temporal structures.…”

“…To pursue these goals, we analysed the longitudinal rates of atrophy on MRI in cortical and subcortical grey matter, with a customized atlas subdivision, which includes regions of interest involved in the pathophysiology of DLB and/or Alzheimer's disease such as basal ganglia, posterior cingulate gyrus and medial temporal lobe, temporal, occipital, parietal and frontal neocortex (Minoshima et al, 2001;Whitwell et al, 2007b;Burton et al, 2009;Teune et al, 2010;Zhong et al, 2014;McCleery et al, 2015;Nedelska et al, 2015;Mak et al, 2016). Furthermore, we investigated whether amyloid-b deposition at baseline is associated with a faster cognitive and functional decline in patients with probable DLB.…”

Vascular factors in Alzheimer’s disease

“…The severity of the disease, the severity of dementia and cognitive impairment, the state of higher mental functions are frequently directly dependent on the severity of atrophic changes in the brain tissue [19,[35][36][37][38]. Thus, patients with pre-clinical TDR-0 stage have 4-8% atrophy of the temporal lobes, but patients with advanced TDR-3 AD stage have 33% -62% atrophy [19,21,22,27], though vascular disorders occurring in the brain during the development of AD are at about the same level among all patients regardless of their TDR group [21,27].…”