Amyloid‐β deposition in cognitively normal oldest‐old is associated with cortical thinning and faster memory decline: Neuroimaging: Neuroimaging predictors of cognitive decline. (7th December 2020)

• Record Type: Journal Article
• Authors: Pelkmans, Wiesje; Legdeur, Nienke; Kate, Mara ten; Yaqub, Maqsood; Barkhof, Frederik; Van Berckel, Bart N.M.; van Der Flier, Wiesje; Visser, Pieter Jelle; Tijms, Betty M.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 4
• Page Start: n/a
• Page End: n/a
• Publication Date: 2020-12-07
• Subjects: Alzheimer's disease -- Periodicals; Alzheimer Disease -- Periodicals; Dementia -- Periodicals; Démence; Maladie d'Alzheimer; Périodique électronique (Descripteur de forme); Ressource Internet (Descripteur de forme); 616.83
• DOI: 10.1002/alz.040991
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: The Alzheimer's disease (AD) pathological cascade is hypothesized to start with the accumulation of amyloid‐β (Aβ). However, the precise effect of Aβ deposition on cognitive decline in the oldest‐old remains controversial, since very old individuals can have intact cognition despite abnormal AD biomarkers. Here we studied, in cognitively normal individuals of 90 years and older, the impact of Aβ on structural brain integrity and the association of Aβ and structural brain integrity on decline over time in memory functioning. Method: Fifty‐seven cognitively normal individuals (age mean±sd = 92.7±2.9) were selected from the EMIF‐AD 90+ study. Aβ status was determined by visual reads on [ 18 F]‐flutemetamol PET (normal=Aβ‐, abnormal=Aβ+); cortical thickness and hippocampal volume were quantified on structural MRI with FreeSurfer and FSL, respectively. Cortical thickness was computed according to the Desikan‐Killany atlas and averaged across hemispheres. Hippocampal volume was normalized for intracranial volume. Memory performance was evaluated using a composite score of the CERAD (delayed recall), Logical Memory (delayed recall), Rey Complex Figure (delayed copy), and the Visual Association Test, that were repeated after 20 months (n=43). Effects of Aβ status, regional cortical thickness, hippocampal volume, time, and their interactions on memory function were assessed with linear mixed models, adjusted for age and sex. Result: Roughly one out of three (n=19; 33%) individuals had an abnormal amyloid PET (Table1). Compared to Aβ‐, those with Aβ+ showed at baseline a thinner parahippocampal and medial orbitofrontal cortex ( p <.05; Fig.1), while hippocampal volume did not differ. Over time, Aβ+ individuals showed a steeper decline ( β ±SE=‐.27±.09; p <.01;) on memory performance than Aβ‐ (Fig.1). Faster memory decline was also predicted by cortical thinning in predominantly temporal regions in the whole group (Fig.1). Conclusion: In the oldest‐old with initially intact cognition, Aβ pathology was associated with a thinner cortex and faster decline in memory performance. These results suggest that Aβ abnormality, even in the oldest old with apparent high reserve and maintenance mechanisms, is indicative of active neurodegeneration. Other pathologies may also contribute to decline in the oldest old as a thinner temporal lobe predicted decline in memory irrespective of Aβ pathology.