Krebs, Christine; Brill, Esther; Minkova, Lora; Federspiel, Andrea; Kellner-Weldon, Frauke; Wyss, Patric; Teunissen, Charlotte E; van Harten, Argonde C; Seydell-Greenwald, Anna; Klink, Katharina; Züst, Marc A; Brem, Anna-Katharine; Klöppel, Stefan (2023). Investigating Compensatory Brain Activity in Older Adults with Subjective Cognitive Decline. Journal of Alzheimer's disease, 93(1), pp. 107-124. IOS Press 10.3233/JAD-221001
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BACKGROUND
Preclinical Alzheimer's disease (AD) is one possible cause of subjective cognitive decline (SCD). Normal task performance despite ongoing neurodegeneration is typically considered as neuronal compensation, which is reflected by greater neuronal activity. Compensatory brain activity has been observed in frontal as well as parietal regions in SCD, but data are scarce, especially outside the memory domain.
OBJECTIVE
To investigate potential compensatory activity in SCD. Such compensatory activity is particularly expected in participants where blood-based biomarkers indicated amyloid positivity as this implies preclinical AD.
METHODS
52 participants with SCD (mean age: 71.00±5.70) underwent structural and functional neuroimaging (fMRI), targeting episodic memory and spatial abilities, and a neuropsychological assessment. The estimation of amyloid positivity was based on plasma amyloid-β and phosphorylated tau (pTau181) measures.
RESULTS
Our fMRI analyses of the spatial abilities task did not indicate compensation, with only three voxels exceeding an uncorrected threshold at p < 0.001. This finding was not replicated in a subset of 23 biomarker positive individuals.
CONCLUSION
Our results do not provide conclusive evidence for compensatory brain activity in SCD. It is possible that neuronal compensation does not manifest at such an early stage as SCD. Alternatively, it is possible that our sample size was too small or that compensatory activity may be too heterogeneous to be detected by group-level statistics. Interventions based on the individual fMRI signal should therefore be explored.