Investigating Compensatory Brain Activity in Older Adults with Subjective Cognitive Decline

Christine Krebs, Esther Brill, Lora Minkova, Andrea Federspiel, Frauke Kellner-Weldon, Patric Wyss, Charlotte E. Teunissen, Argonde C. van Harten, Anna Seydell-Greenwald, Katharina Klink, Marc A. Züst, Anna-Katharine Brem, Stefan Klöppel

Research output: Contribution to journalArticleAcademicpeer-review


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.

Original languageEnglish
Pages (from-to)107-124
Number of pages18
JournalJournal of Alzheimer's disease : JAD
Issue number1
Publication statusPublished - 2 May 2023


  • Blood-based biomarkers
  • episodic memory
  • functional MRI
  • neuronal compensation
  • spatial abilities
  • subjective cognitive decline

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