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Cognitive and neuroimaging features and brain β-amyloidosis in individuals at risk of Alzheimer's disease (INSIGHT-preAD): a longitudinal observational study

2018; Elsevier BV; Volume: 17; Issue: 4 Linguagem: Inglês

10.1016/s1474-4422(18)30029-2

1474-4465

Bruno Dubois, Stéphane Epelbaum, Francis Nyasse, Hovagim Bakardjian, Geoffroy Gagliardi, Olga Uspenskaya, Marion Houot, Simone Lista, Federica Cacciamani, Marie‐Claude Potier, Anne Bertrand, Foudil Lamari, Habib Benali, Jean‐François Mangin, Olivier Colliot, Remy Genthon, Marie‐Odile Habert, Harald Hampel, Christelle Audrain, Alexandra Auffret, Filippo Baldacci, Ismahane Benakki, Hugo Bertín, Laurie Boukadida, Enrica Cavedo, Patrizia A. Chiesa, Luce Dauphinot, Antonio Dos Santos, Marion Dubois, Stanley Durrleman, Gaëlle Fontaine, Alexis Génin, Pauline Glasman, Navichka Jungalee, Aurélie Kas, M. Kilani, Valentina La Corte, Stéphane Lehéricy, Claire Letondor, Marcel Levy, Mark Lowrey, Juliette Ly, Ornella Makiese, Christiane Metzinger, Agnès Michon, Fanny Mochel, Catherine Poisson, Stéphie Ratovohery, Marie Revillon, Katrine Rojkova, Perrine Roy, Katia Santos-Andrade, Rachel Schindler, Laure Seux, Valérie Simon, Marine Sole, Caroline Tandetnik, Marc Teichmann, Michel Thiebaut de Shotten, Nadjia Younsi,

Diet and metabolism studies

Background Improved understanding is needed of risk factors and markers of disease progression in preclinical Alzheimer's disease. We assessed associations between brain β-amyloidosis and various cognitive and neuroimaging parameters with progression of cognitive decline in individuals with preclinical Alzheimer's disease. Methods The INSIGHT-preAD is an ongoing single-centre observational study at the Salpêtrière Hospital, Paris, France. Eligible participants were age 70–85 years with subjective memory complaints but unimpaired cognition and memory (Mini-Mental State Examination [MMSE] score ≥27, Clinical Dementia Rating score 0, and Free and Cued Selective Reminding Test [FCSRT] total recall score ≥41). We stratified participants by brain amyloid β deposition on 18F-florbetapir PET (positive or negative) at baseline. All patients underwent baseline assessments of demographic, cognitive, and psychobehavioural, characteristics, APOE ε4 allele carrier status, brain structure and function on MRI, brain glucose-metabolism on 18F-fluorodeoxyglucose (18F-FDG) PET, and event-related potentials on electroencephalograms (EEGs). Actigraphy and CSF investigations were optional. Participants were followed up with clinical, cognitive, and psychobehavioural assessments every 6 months, neuropsychological assessments, EEG, and actigraphy every 12 months, and MRI, and 18F-FDG and 18F-florbetapir PET every 24 months. We assessed associations of amyloid β deposition status with test outcomes at baseline and 24 months, and with clinical status at 30 months. Progression to prodromal Alzheimer's disease was defined as an amnestic syndrome of the hippocampal type. Findings From May 25, 2013, to Jan 20, 2015, we enrolled 318 participants with a mean age of 76·0 years (SD 3·5). The mean baseline MMSE score was 28·67 (SD 0·96), and the mean level of education was high (score >6 [SD 2] on a scale of 1–8, where 1=infant school and 8=higher education). 88 (28%) of 318 participants showed amyloid β deposition and the remainder did not. The amyloid β subgroups did not differ for any psychobehavioural, cognitive, actigraphy, and structural and functional neuroimaging results after adjustment for age, sex, and level of education More participants positive for amyloid β deposition had the APOE ε4 allele (33 [38%] vs 29 [13%], p<0·0001). Amyloid β1–42 concentration in CSF significantly correlated with mean 18F-florbetapir uptake at baseline (r=–0·62, p<0·0001) and the ratio of amyloid β1–42 to amyloid β1–40 (r=–0·61, p<0·0001), and identified amyloid β deposition status with high accuracy (mean area under the curve values 0·89, 95% CI 0·80–0·98 and 0·84, 0·72–0·96, respectively). No difference was seen in MMSE (28·3 [SD 2·0] vs 28·9 [1·2], p=0·16) and Clinical Dementia Rating scores (0·06 [0·2] vs 0·05 [0·3]; p=0·79) at 30 months (n=274) between participants positive or negative for amyloid β. Four participants (all positive for amyloid β deposition at baseline) progressed to prodromal Alzheimer's disease. They were older than other participants positive for amyloid β deposition at baseline (mean 80·2 years [SD 4·1] vs 76·8 years [SD 3·4]) and had greater 18F-florbetapir uptake at baseline (mean standard uptake value ratio 1·46 [SD 0·16] vs 1·02 [SD 0·20]), and more were carriers of the APOE ε4 allele (three [75%] of four vs 33 [39%] of 83). They also had mild executive dysfunction at baseline (mean FCSRT free recall score 21·25 [SD 2·75] vs 29·08 [5·44] and Frontal Assessment Battery total score 13·25 [1·50] vs 16·05 [1·68]). Interpretation Brain β-amyloidosis alone did not predict progression to prodromal Alzheimer's disease within 30 months. Longer follow-up is needed to establish whether this finding remains consistent. Funding Institut Hospitalo-Universitaire and Institut du Cerveau et de la Moelle Epinière (IHU-A-ICM), Ministry of Research, Fondation Plan Alzheimer, Pfizer, and Avid.