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Publication Detail
Abnormal Regional and Global Connectivity Measures in Subjective Cognitive Decline Depending on Cerebral Amyloid Status
  • Publication Type:
    Working discussion paper
  • Authors:
    Li S, Daamen M, Scheef L, Gaertner F, Buchert R, Buchmann M, Buerger K, Catak C, Dobisch L, Drzezga A, Ertl-Wagner B, Essler M, Fliessbach K, Haynes JD, Incesoy EI, Kilimann I, Krause B, Lange C, Laske C, Priller J, Ramirez A, Reimold M, Rominger A, Roy N, Scheffler K, Schmitt A, Schneider A, Spottke A, Spruth EJ, Teipel S, Tscheuschler M, Wagner M, Wolfsgruber S, Düzel E, Jessen F, Peters O, Boecker H
  • Publication date:
    13/02/2020
  • Status:
    Published
Abstract

Background:

While cerebral beta-amyloid accumulation was found in many studies to alter precuneus-based functional connectivity (FC) in mild cognitive impairment and demented Alzheimer’s disease (AD) patients, its impact is less well understood in subjective cognitive decline (SCD), which in the presence of underlying AD pathologic change corresponds to a progression to stage 2 of the clinical Alzheimer’s continuum in the 2018 National Institute on Aging and Alzheimer’s Association research framework, and represents the earliest clinical manifestation of AD.

Methods:

From the DELCODE (DZNE – Longitudinal Cognitive Impairment and Dementia Study) cohort, two groups of 24 age- and gender-matched amyloid-positive SCD (SCD Aβ+ ) and amyloid-negative SCD (SCD Aβ- ) patients were selected according to visual [18F]-Florbetaben PET readings, and studied with resting-state BOLD fMRI. Local (regional homogeneity (ReHo), amplitude of low-frequency fluctuation (ALFF) and fractional ALFF (fALFF)) and global (degree centrality (DC), precuneus seed-based FC maps) measures were calculated and compared between both groups. Furthermore, follow-up correlation analyses probed linear relationships of observed group differences with global as well as precuneal amyloid load measured by Florbetaben standard uptake value ratios (SUVR FBB ).

Results:

For the local measures, ReHo was significantly higher in the bilateral precuneus for the SCD Aβ+ group, whereas ALFF and fALFF measures were not altered between groups. For the global measures, relatively higher precuneus-based FC with occipital areas (but no altered DC) was observed in the SCD Aβ+ group. Moreover, the FC differences between precuneus and occipital areas were positively correlated with global (SCD Aβ+ ) and local precuneus SUVR FBB (both groups).

Conclusions:

While confounding influences due to a higher ratio of APOE e4 carriers in the SCD Aβ+ group cannot be excluded, results indicate functional alterations in the precuneus hub region that were linearly related to beta-amyloid load, highlighting incipient pathology and possible compensatory mechanisms in stage 2 of the AD continuum.
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