Jack, Clifford R

BackgroundThe progressive supranuclear palsy syndrome (PSPS) and corticobasal syndrome (CBS) are associated with relatively specific patterns of atrophy; the former predominantly involving the brainstem, the latter frontoparietal regions. However, it has become apparent that there are subjects that meet criteria for PSPS and CBS. We refer to subjects with this presentation as Hybrids. The hybrid presentation is not rare, yet there are no studies that have assessed the neuroanatomical correlates of the hybrid syndrome to explain its occurrence.MethodIn this study of 41 subjects and controls, we utilized the technique of voxel‐based morphometry to assess both gray and white matter volume loss in six prospectively recruited Hybrids that underwent 3.0 T volumetric head magnetic resonance image scanning to determine the neuroanatomical correlates of the syndrome. We compared patterns of atrophy in three prospectively recruited groups: the Hybrid group (n = 6), a PSPS group (n = 10), and CBS group (n = 5). All 21 subjects had completed the same standardized batteries assessing cognition, and motor, behavioral, executive, oculomotor and limb praxis function.ResultsThe Hybrid group showed imaging features of both PSPS and CBS, with volume loss observed in the brainstem (superior cerebellar peduncle) and cortex (medial and lateral premotor, prefrontal and motor cortex). As expected, typical patterns of loss were observed in PSPS and CBS.ConclusionsThese findings explain the neuroanatomical basis of the overlapping presenting signs and symptoms of PSPS and CBS, in Hybrids.

Drugs aimed at the initial stages of the Alzheimer’s disease pathology should be tested a decade before the onset of dementia.

BackgroundThe promise of Alzheimer's disease biomarkers has led to their incorporation in new diagnostic criteria and in therapeutic trials; however, significant barriers exist to widespread use. Chief among these is the lack of internationally accepted standards for quantitative metrics. Hippocampal volumetry is the most widely studied quantitative magnetic resonance imaging measure in Alzheimer's disease and thus represents the most rational target for an initial effort at standardization.Methods and ResultsThe authors of this position paper propose a path toward this goal. The steps include the following: (1) Establish and empower an oversight board to manage and assess the effort, (2) adopt the standardized definition of anatomic hippocampal boundaries on magnetic resonance imaging arising from the European Alzheimer's Disease Centers–Alzheimer's Disease Neuroimaging Initiative hippocampal harmonization effort as a reference standard, (3) establish a scientifically appropriate, publicly available reference standard data set based on manual delineation of the hippocampus in an appropriate sample of subjects (Alzheimer's Disease Neuroimaging Initiative), and (4) define minimum technical and prognostic performance metrics for validation of new measurement techniques using the reference standard data set as a benchmark.ConclusionsAlthough manual delineation of the hippocampus is the best available reference standard, practical application of hippocampal volumetry will require automated methods. Our intent was to establish a mechanism for credentialing automated software applications to achieve internationally recognized accuracy and prognostic performance standards that lead to the systematic evaluation and then widespread acceptance and use of hippocampal volumetry. The standardization and assay validation process outlined for hippocampal volumetry was envisioned as a template that could be applied to other imaging biomarkers.