A Systematic Review of Neuroimaging Studies Comparing Individuals with Subjective Cognitive Decline to Healthy Controls

Background: Individuals with subjective cognitive decline (SCD) are hypothesized to be the earliest along the cognitive continuum between healthy aging and Alzheimer's disease (AD), although more research is needed on this topic. Given that treatment approaches may be most effective pre-clinically, a primary objective of emerging research is to identify biological markers of SCD using neuroimaging methods. Objective: The current review aimed to comprehensively present the neuroimaging studies on SCD to date. Methods: PubMed and PsycINFO databases were searched for neuroimaging studies of individuals with SCD. Quality assessments were completed using the Appraisal tool for Cross-Sectional Studies. Results: In total, 62 neuroimaging studies investigating differences between participants with SCD and healthy controls were identified. Specifically, the number of studies were as follows: 36 MRI, 6 PET, 8 MRI/PET, 4 EEG, 7 MEG, and 1 SPECT. Across neuroimaging modalities, 48 of the 62 included studies revealed significant differences in brain structure and/or function between groups. Conclusion: Neuroimaging methods can identify differences between healthy controls and individuals with SCD. However, inconsistent results were found within and between neuroimaging modalities. Discrepancies across studies may be best accounted for by methodological differences, notably variable criteria for SCD, and differences in participant characteristics and risk factors for AD. Clinic based recruitment and cross-sectional study design were common and may bias the literature. Future neuroimaging investigations of SCD should consistently incorporate the standardized research criteria for SCD (as recommended by the SCD-Initiative), include more details of their SCD sample and their symptoms, and examine groups longitudinally.