Multifaceted pattern of longitudinal imaging changes in cognitively normal midlife adults: The PREVENT‐Dementia study: Early imaging changes in cognitively normal subjects at risk of late onset AD. (7th December 2020)

• Record Type: Journal Article
• Authors: Mak, Elijah; Dounavi, Maria‐Eleni; Low, Audrey; McKiernan, Elizabeth; Carter, Stephen F; Newton, Coco; Williams, Guy B; Ritchie, Karen; Wells, Katie; Sahin, Zeynep; Carriere, Isabelle; Terrera, Graciela Muniz; Ritchie, Craig W.; Su, Li; O'Brien, John T.
• Is Part Of: Alzheimer's & dementia. Volume 16(2020)Supplement 5
• 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.042942
• Languages: English
• ISSNs: 1552-5260

Abstract

Abstract: Background: First‐degree relatives of people with dementia (FH+) are at increased risk of developing Alzheimer's disease (AD). Identifying preclinical brain changes would facilitate both early quantifiable longitudinal disease monitoring and interventional trials. However, the literature of imaging changes in FH+ remains highly controversial. We aim to investigate "estimated years to onset of dementia" (EYOD) as a surrogate marker of preclinical progression and assessed whether FH+ approaching the onset of dementia would express more severe patterns of longitudinal brain changes. Method: 89 FH+ persons underwent serial 3T‐MRI with T1‐MPRAGE, DWI and ASL (mean interval: 2 years). The longitudinal Freesurfer pipeline was used to segment hippocampal subfields and early‐AD regions. Partial‐volume corrected ASL data and DWI data were processed with FSL‐BASIL4 and DTI‐TK5. Small vessel disease was indexed with white matter hyperintensities (WMHs) (Figure 1). We applied linear mixed effects models with random intercepts to predict MRI changes relative to baseline EYOD, accounting for baseline age, gender, education and time from baseline. Secondary analyses examined the interaction of APOE‐ε4+ on proximity‐related brain changes. Result: A shorter EYOD was associated with progressive decrease in FA, increase in MD/RD and atrophy of the fusiform gyrus over time (Figure 2). Interaction analyses revealed that APOE‐ε4+ carriers showed significant longitudinal atrophy of the hippocampal subfields with shorter EYOD. In contrast, cortical perfusion increased before plateauing ∼10 years before estimated onset. There were no associations of EYOD with mean cortical thickness or WMHs (See Figure 3 for a summary of main findings). Conclusion: Our findings represent an extensive characterisation of longitudinal brain changes associated with proximity to dementia in FH+. Individuals who are approaching their parental age of dementia onset may be showing incipient brain abnormalities, particularly amongst APOE‐ε4 carriers. The involvement of early‐AD regions also confer support to the biological validity of EYOD as a stage marker of preclinical progression. Further clinical follow‐up of our sample would provide critical validation of these findings.