Reference standard space hippocampus labels according to the EADC-ADNI harmonized protocol: Utility in automated volumetry

BACKGROUND: A harmonized protocol (HarP) for manual hippocampal segmentation on magnetic resonance imaging (MRI) has recently been developed by an international European Alzheimer's Disease Consortium–Alzheimer's Disease Neuroimaging Initiative project. We aimed at providing consensual certified HarP hippocampal labels in Montreal Neurological Institute (MNI) standard space to serve as reference in automated image analyses. METHODS: Manual HarP tracings on the high-resolution MNI152 standard space template of four expert certified HarP tracers were combined to obtain consensual bilateral hippocampus labels. Utility of these reference labels is demonstrated in a simple atlas-based morphometry approach for automated calculation of HarP-compliant hippocampal volumes within SPM software. RESULTS: Individual tracings showed very high agreement among the five expert tracers (pairwise Jaccard indices 0.82–0.87). Automatically calculated hippocampal volumes were highly correlated (rL/R = 0.89/0.91) with gold standard volumes in the HarP benchmark data set (N = 135 MRIs), with a mean volume difference of 9% (standard deviation 7%). CONCLUSION: The consensual HarP hippocampus labels in the MNI152 template can serve as a reference standard for automated image analyses involving MNI standard space normalization

Longitudinal Accumulation of Cerebral Microhemorrhages in Dominantly Inherited Alzheimer Disease

Objective: To investigate the inherent clinical risks associated with the presence of cerebral microhemorrhages (CMHs) or cerebral microbleeds (CMBs) and characterize individuals at high risk for developing hemorrhagic amyloid-related imaging abnormality (ARIA-H), we evaluated longitudinally families affected by dominantly inherited Alzheimer disease (DIAD). Methods: Mutation carriers (n=310) and non-carriers (n=201) underwent neuroimaging, including gradient echo MR sequences to detect CMHs, neuropsychological, and clinical assessments. Cross-sectional and longitudinal analyses evaluated relationships between CMHs and neuroimaging and clinical marker of disease. Results: Three percent of non-carriers and eight percent of carriers developed CMHs primarily located in lobar areas. Carriers with CMHs were older, had higher diastolic blood pressure and Hachinski ischemic scores, and more clinical, cognitive, and motor impairments than those without CMH. APOE-ε4 status was not associated with the prevalence or incidence of CMHs. Prevalent or incident CMHs predicted faster change in clinical dementia rating although not composite cognitive measure, cortical thickness, hippocampal volume, or white matter lesions. Critically, the presence of two or more CMHs was associated with a significant risk for development of additional CMHs over time (8.95±10.04 per year). Conclusion: Our study highlights factors associated with the development of CMHs in individuals with DIAD. CMHs are a part of the underlying disease process in DIAD and are significantly associated with dementia. This highlights that in participants in treatment trials exposed to drugs, which carry the risk of ARIA-H as a complication, it may be challenging to separate natural incidence of CMHs from drug related CMHs