Section:
New Results
Cognitive and neuroimaging features and brain amyloidosis in individuals at risk of Alzheimer's disease
Participants :
Bruno Dubois [Correspondant] , 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.
Improved understanding is needed of risk factors and markers of disease progression in preclinical Alzheimer's disease. We assessed associations between brain amyloidosis and various cognitive and neuroimaging parameters with progression of cognitive decline in individuals with preclinical Alzheimer's disease. 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 , Clinical Dementia Rating score
0, and Free and Cued Selective Reminding Test [FCSRT] total recall score ). We
stratified participants by brain amyloid deposition on 18F-florbetapir PET
(positive or negative) at baseline. All patients underwent baseline assessments
of demographic, cognitive, and psychobehavioural, characteristics, APOE 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 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. 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 (28showed amyloid deposition and the remainder did not. The amyloid 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 deposition had the APOE
allele (33 [38%] vs 29 [13%], p<0·0001). Amyloid concentration in CSF
significantly correlated with mean 18F-florbetapir uptake at baseline (r=-0·62,
p<0·0001) and the ratio of amyloid to amyloid (r=-0·61, p<0·0001),
and identified amyloid 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. Four participants (all
positive for amyloid deposition at baseline) progressed to prodromal
Alzheimer's disease. They were older than other participants positive for amyloid
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 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]).
Brain 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.
More details in [13].