Data‐driven analysis of most common neurodegenerative dementias reveals atrophy patterns associated with overlapping cognitive symptoms
Authors: Venkatraghavan Vikram , Bocancea Diana I. , den Braber Anouk , Dubbelman Mark A. , Jiang Chenyang , Coomans Emma M. , van Unnik Annemartijn A. J. M. , van Veen Julia M.L. , Ribberink Marieke , Reijner Niels , Saddal Shalina , Mastenbroek Sophie E , van Gils Aniek M. , Kluin Caro M. , de Leeuw Diederick Martijn , Vromen Eleonora M. , Bekkers Lotta , Georgallidou Margarita , van der Landen Sophie M. , Baumann Janna M. , Heuvelink Joost , Reus Lianne M. , Lorenzini Luigi , Kamps Suzie , Bouman Sophie P.H. , Singleton Ellen Hanna , de Boer Sterre C.M. , Rousset Rebecca Z. , Kuijper Bart , Verhagen Eline , Smit Dimas , Rikken Roos M. , Sikkes Sietske A.M. , Visser Pieter Jelle , Bouwman Femke H. , Barkhof Frederik , Lemstra Afina W. , Pijnenburg Yolande A.L. , van der Flier Wiesje M. , Tijms Betty M. 
Published: December 2023

Background

A precise understanding of the neuroanatomical basis of clinical manifestation of dementia is an important step for timely diagnosis. Dementia due to proteinopathies, such as Alzheimer’s disease (AD), dementia with Lewy bodies (DLB), and Frontotemporal dementia (FTD), have different yet overlapping atrophy patterns which could account for their overlapping clinical presentations. To disentangle these relationships and facilitate timely differential diagnosis, we estimated distinct and overlapping atrophy patterns and associated them with cognitive deficits.

Method

We included 1702 AD (age = 66.1±8.3), 319 FTD (age = 63.3±7.7), 213 DLB (age = 69.7±7.0), and 1330 subjective cognitive decline (SCD) (age = 59.8±9.0) participants from the Amsterdam Dementia Cohort. MRIs were processed with Freesurfer and outputs were manually checked. Scanner‐related bias in outputs was corrected using NeuroHarmony pipeline. Participants’ cognition was evaluated using standardized neuropsychological tests. Z‐scores for cognitive domains of memory, executive functioning, attention, language, and visuospatial functioning were derived using SCD group as reference. We estimated distinct and overlapping atrophy patterns in each disease by computing odds ratio in each region, using SCD group as reference. Furthermore, we computed group‐wise Pearson partial correlation between the (sub‐)cortical measures and cognition while correcting for confounding effects of age, sex, and education level.

Result

Atrophy in bilateral inferior temporal, and right hippocampus was more prevalent in AD and FTD patients than in DLB patients (Figures 1‐3). Temporal pole atrophy was more prevalent in FTD than in AD or DLB patients. Superior parietal and supra marginal atrophy was more prevalent in AD than in FTD or DLB patients. Bilateral hippocampus and amygdala atrophy associated with memory impairment in AD, whereas left hemisphere atrophy associated with memory impairment in FTD. Frontal atrophy associated with worse executive functioning and attention in FTD, but not in AD. Language deficit associated with left temporal lobe atrophy in both FTD and AD. Visuospatial dysfunction associated with parietal lobe atrophy in both AD and FTD. In DLB, we observed no significant correlation between atrophy and cognitive deficits.

Conclusion

We identified distinct and overlapping atrophy patterns and associations of atrophy patterns with cognitive deficits in AD, FTD, and DLB. These data‐driven insights are crucial for accurate diagnosis and prognosis.