Three subtypes of Alzheimer’s disease have been defined on the basis of neurofibrillary tangle distribution. These are typical Alzheimer, hippocampal-sparing Alzheimer, and limbic-predominant Alzheimer subtypes. Compared with typical Alzheimer’s, hippocampal-sparing Alzheimer’s has more neurofibrillary tangles in the cortex and fewer in the hippocampus. The opposite pattern is seen in limbic-predominant Alzheimer’s. The purpose of this study was to determine whether MRI patterns of atrophy differed between these three subtypes and whether structural neuroimaging was predictive of subtype at autopsy.

Cases were assigned to one of these three pathological subtypes on the basis of neurofibrillary tangle counts in hippocampus and cortex and ratio of hippocampal to cortical burden, without reference to neuronal loss. Voxel-based morphometry and atlas-based parcellation were used to compare patterns of grey matter loss between groups and with age-matched control individuals.

Of the 177 patients studied, 71% were classified as having typical Alzheimer, 19% as having limbic-predominant Alzheimer, and 11% as having hippocampal-sparing Alzheimer subtype. Most patients with typical (78%) and limbic-predominant Alzheimer’s (94%) initially presented with an amnestic syndrome, but fewer patients with hippocampal-sparing Alzheimer’s (42%) did. The most severe medial temporal atrophy was recorded in patients with limbic-predominant Alzheimer’s, followed by those with typical disease subtype, and then those with hippocampal-sparing Alzheimer’s. Conversely, the most severe cortical atrophy was noted in patients with hippocampal-sparing Alzheimer’s, followed by those with typical disease subtype, and then limbic-predominant Alzheimer’s. The authors found that the ratio of hippocampal to cortical volumes allowed the best discrimination between subtypes. Patients with typical Alzheimer’s and non-amnesic initial presentation had a significantly higher ratio of hippocampal to cortical volumes than did those with an amnesic presentation.

The authors concluded that patterns of atrophy on MRI differed across the three Alzheimer subtypes. MRI regional volumetric analysis can reliably track the distribution of neurofibrillary tangle pathology and can predict pathological subtype of Alzheimer’s disease at autopsy.

Whitwell JL, Dickson DW, Murray ME, Weigand SD, Tosakulwong N, Senjem ML, Knopman DS, Boeve BF, Parisi JE, Petersen RC, Jack CR Jr, and Josephs KA: Neuroimaging correlates of pathologically defined subtypes of Alzheimer’s disease: a case-control study. Lancet Neurology 11(10): 868-877 (2012).

http://www.ncbi.nlm.nih.gov/pubmed/22951070

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