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Progression modelling of cognitive decline and associated FDG‐PET imaging features in Alzheimer’s disease
Author(s) -
Prosser Angus,
Evenden Dave,
Holmes Robin,
Kipps Christopher
Publication year - 2020
Publication title -
alzheimer's and dementia
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 6.713
H-Index - 118
eISSN - 1552-5279
pISSN - 1552-5260
DOI - 10.1002/alz.045900
Subject(s) - clinical dementia rating , statistical parametric mapping , dementia , neuroimaging , cognitive decline , medicine , positron emission tomography , alzheimer's disease neuroimaging initiative , disease , psychology , radiology , magnetic resonance imaging , psychiatry
Background Prognosis for Alzheimer’s disease is difficult, with rates of disease progression varying widely. Despite the extensive use of clinical dementia severity assessment scales to determine dementia diagnosis and to monitor progression, there is no consensus on which imaging factors may accurately predict future decline trajectories on these measures. Determination of baseline imaging patterns that are related to slower, or faster, decline rates could be used to identify those at highest risk of worse outcomes and inform care planning. Method Decline trajectories were estimated from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) dataset which contains clinical, imaging, and biological assessment records for 1,736 patients followed‐up over 8 years at 3, 6, or 12 month intervals. Clusters of similar decline trajectories were identified for patients with relevant baseline fluorodeoxyglucose positron emission tomography (FDG‐PET) imaging data (N=530) using mini‐mental state examination (MMSE), clinical dementia rating sum of boxes (CDR‐SB), Alzheimer’s disease assessment scale (ADAS‐13), and functional activities questionnaire (FAQ) assessment scores. Decline trajectories allocated to slow , intermediate , and fast clusters were further analysed to find significant associations with PET imaging features using statistical parametric mapping (SPM12). Result When compared to cognitively normal non‐decliners, slow , intermediate and fast cluster groups showed similar topographic patterns of hypometabolism on FDG‐PET for all four clinical assessments (p<0.05 family‐wise error corrected). Slow progressors showed focal hippocampal hypometabolism, which extended into parietotemporal, inferior parietal and precuneal regions for intermediate progressors. Fast progressors showed more extensive hypometabolism in similar regions with additional superior frontal hypometabolism. Although locational deficits were similar on cognitive measures for decline groups, CDR‐SB showed the greatest hypometabolism extent for slow progressors, followed by FAQ, then ADAS‐13, with MMSE showing the least. Conclusion Our results suggest a single pattern of pathological progression of functional degeneration in Alzheimer’s disease, with slow , intermediate and fast progressors at different time points on the same decline trajectory. This progression begins with focal medial temporal regional abnormalities, extending to parietotemporal, inferior parietal and precuneus regions, before finally involving the superior frontal lobe. CDR‐SB was the most sensitive in detecting slow progressor abnormality, with MMSE being the least sensitive.