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Self-reported cognitive decline seen on imaging despite unimpaired objective assessment

30 June, 2021  

Despite a normal objective assessment, MR imaging can detect reduced neural connectivity among those who self-report cognitive decline.

Subjective cognitive decline (SCD) has been defined as the presence of cognitive complaints in the absence of pathological neuropsychological testing. Furthermore, it has been suggested that the presence of SCD could be an early symptomatic manifestation of Alzheimer’s disease. Nevertheless, while studies have suggested that a decline in functional connectivity can be observed in patients with SCD compared to healthy controls, there is a lack of longitudinal imaging studies of functional connectivity. This led a team from the Department of Psychology, Wayne State University, Detroit, US, to examine the trajectories of functional connectivity over an 18-month period among cognitively unimpaired individuals with varying degrees of SCD. Baseline magnetic resonance imaging was performed on all participants and a subgroup were included in two subsequent scans approximately every one and a half years. The researchers used the memory functioning questionnaire frequency of forgetting (MFQ-FoF) sub-scale, which can be used to assess how frequently individuals they find remembering names, directions, dates etc. are problematic, with higher scores indicating greater difficulty. In addition, participants were assessed using the mini-mental state exam (MMSE) which is a practical method for grading the cognitive state of patients.

Baseline MR imaging was undertaken with a total of 69 adults with an average age of 68.3 years (81% female), of whom, 49 were enrolled in the longitudinal arm of the study. Interestingly, 49% of the original cohort reported a family history of Alzheimer’s disease. The mean score on the MFQ-FOF scale was 2.99 (out of a possible 6). Although 49 were included in the longitudinal arm, of these, only 34 returned for a second scan and 28 had a third measurement. Despite SCD, all participants score more than 25 on the MMSE which is considered within the normal range. The results from the MR imaging revealed reduced functional connectivity in several regions and these reductions were significantly associated with a higher MFQ-FoF, reflecting greater impairment. This reduced functional connectivity was found between the left hippocampus and dorsomedial prefrontal cortex, areas thought to be important for long-term memory processes. Additional reductions in FC were seen between the left hippocampus and lingual gyrus/calcarine sulcus, which, the authors suggested, might reflect disrupted flow of visual information to the hippocampus and thus affect visual memory processing. Finally, there was reduced functional connectivity observed between the right hippocampus and the dorsomedial prefrontal cortex, which suggested disruption in long-term memory processing and again, might account for the observed perception of declining cognitive ability.

The authors concluded that their results suggested that the observed brain changes in functional connectivity, without obvious concomitant objective changes in cognitive function, might serve as a sensitive marker for nascent dementia before it can be detected through independent assessment.

Viviano RP et al, Longitudinal change in hippocampal and dorsal anterior insulae functional connectivity in subjective cognitive decline. Alzheimer’s Res Ther 2021