Abstract
Alzheimer's continuum biological profiles (A+T−N−, A+T+N−, A+T−N+, and A+T+N+) were established in the 2018 National Institute on Aging and Alzheimer's Association research framework for Alzheimer's disease (AD). We aim to assess the relation between AT(N) biomarker profiles and brain functional connectivity (FC) and assess the neural correlates of anosognosia. We assessed local functional coupling and between-network connectivity through between-group intrinsic local correlation and independent component analyses. The neural correlates of anosognosia were assessed via voxel-wise linear regression analysis in prodromal AD. Statistical significance for the FC analysis was set at p ≤ 0.05 false discovery rate (FDR)-corrected for cluster size. One hundred and twenty-one and 73 participants were included in the FC and the anosognosia analysis, respectively. The FC in the default mode network is greater in prodromal AD than AD with dementia (i.e., local correlation: T = 8.26, p-FDR < 0.001, k = 1179; independent component analysis: cerebellar network, T = 4.01, p-FDR = 0.0012, k = 493). The default mode network is persistently affected in the early stages of Alzheimer's biological continuum. The anterior cingulate cortex (T = 2.52, p-FDR = 0.043, k = 704) is associated with anosognosia in prodromal AD.
Highlights
The Alzheimer's disease (AD) continuum is both clinical and biological
We report that using biological definitions, the default mode network (DMN) connectivity is persistently affected in the early stages of the Alzheimer's biological continuum, which is on par with findings from clinically defined groups in the AD continuum
We associate anosognosia to functional connectivity (FC) changes in the anterior cingulate cortex (ACC) in prodromal AD and between the ACC and different brain networks, pointing to the importance of the ACC in the perception of awareness of memory deficits and how brain FC changes in this region might precede changes found in the posterior cingulate cortex (PCC), a DMN region typically associated in AD with anosognosia
Summary
The Alzheimer's disease (AD) continuum is both clinical and biological. The cognitive decline continuum associated with AD is clinically divided into a preclinical, a prodromal, and a clinical stage (Sperling et al, 2011). The AD biological continuum has been recently defined. In 2018, the research framework for a Authors’ contributions: J.D.M. contributed to conceptualization; methodology; software; formal analysis; investigation; data curation; writing, reviewing, and editing the article; visualization; and funding acquisition. N.M.M. contributed to conceptualization; methodology; validation; formal analysis; data curation; writing, reviewing, and editing the article; visualization; project administration; and supervision. P.P.D. contributed to conceptualization; methodology; validation; formal analysis; data curation; writing, reviewing, and editing the article; project administration; and supervision
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
