Journal Article

Applicability of in vivo staging of regional amyloid burden in a cognitively normal cohort with subjective memory complaints: the INSIGHT-preAD study

Hampel, Harald, Habert, Marie-Odile, Gonzalez-Escamilla, Gabriel, Teipel, Stefan, Dubois, Bruno, Cavedo, Enrica, Sakr, Fatemah A., Grothe, Michel J., Bertin, Hugo, Jelistratova, Irina, Locatelli, Maxime, Lehericy, Stephane, Dyrba, Martin

2019

Overview

Background Current methods of amyloid PET interpretation based on the binary classification of global amyloid signal fail to identify early phases of amyloid deposition. A recent analysis of 18F-florbetapir PET data from the Alzheimer’s disease Neuroimaging Initiative cohort suggested a hierarchical four-stage model of regional amyloid deposition that resembles neuropathologic estimates and can be used to stage an individual’s amyloid burden in vivo. Here, we evaluated the validity of this in vivo amyloid staging model in an independent cohort of older people with subjective memory complaints (SMC). We further examined its potential association with subtle cognitive impairments in this population at elevated risk for Alzheimer’s disease (AD). Methods The monocentric INSIGHT-preAD cohort includes 318 cognitively intact older individuals with SMC. All individuals underwent 18F-florbetapir PET scanning and extensive neuropsychological testing. We projected the regional amyloid uptake signal into the previously proposed hierarchical staging model of in vivo amyloid progression. We determined the adherence to this model across all cases and tested the association between increasing in vivo amyloid stage and cognitive performance using ANCOVA models. Results In total, 156 participants (49%) showed evidence of regional amyloid deposition, and all but 2 of these (99%) adhered to the hierarchical regional pattern implied by the in vivo amyloid progression model. According to a conventional binary classification based on global signal (SUVR Cereb  = 1.10), individuals in stages III and IV were classified as amyloid-positive (except one in stage III), but 99% of individuals in stage I and even 28% of individuals in stage II were classified as amyloid-negative. Neither in vivo amyloid stage nor conventional binary amyloid status was significantly associated with cognitive performance in this preclinical cohort. Conclusions The proposed hierarchical staging scheme of PET-evidenced amyloid deposition generalizes well to data from an independent cohort of older people at elevated risk for AD. Future studies will determine the prognostic value of the staging approach for predicting longitudinal cognitive decline in older individuals at increased risk for AD.

• Publisher: BioMed Central,BioMed Central Ltd,Springer Nature B.V,BMC
• Subject: Aged / Aged, 80 and over / Alzheimer Disease - diagnostic imaging / Alzheimer Disease - metabolism / Alzheimer Disease - psychology / Alzheimer's disease / Amyloid - metabolism / Amyloid PET / Analysis / Biomedicine / Brain research / Cerebellum / Classification / Cognition - physiology / Cognitive Dysfunction - diagnostic imaging / Cognitive Dysfunction - metabolism / Cognitive Dysfunction - psychology / Cohort Studies / Complaints / Dementia / Diagnostic Self Evaluation / Elderly / Female / Florbetapir / Follow-Up Studies / Future predictions / Geriatric Psychiatry / Geriatrics/Gerontology / Humans / In vivo staging / Life Sciences / Male / Medical imaging / Memory / Memory - physiology / Mental Status and Dementia Tests / Motor cortex / Neurobiology / Neurology / Neurons and Cognition / Neurosciences / Older people / Positron emission tomography / Subjective memory complaint