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Meta-analysis finds distinct fMRI activation patterns in MCI and Alzheimer's disease during cognitive tasks

Meta-analysis finds distinct fMRI activation patterns in MCI and Alzheimer's disease during cognitiv…
Photo by Dmytro Vynohradov / Unsplash
Key Takeaway
Note distinct fMRI activation patterns in MCI and AD, but findings are associative from observational data.

This coordinate-based meta-analysis (activation likelihood estimation, ALE) synthesized data from 90 task-based functional MRI (fMRI) studies involving 2824 participants, including patients with mild cognitive impairment (MCI), Alzheimer's disease (AD), and healthy controls (HC). The analysis examined brain activation patterns during cognitive tasks across four domains, comparing patients to HC to identify spatially convergent regions of aberrant activation or hypoactivation.

In patients with MCI, significant activation clusters across memory tasks and all tasks combined were observed. Meta-analytic functional decoding suggested these clusters were linked to spatial and phonological processing, overlapping with dorsal attention and frontoparietal networks. In patients with AD, significant activation convergence was found specifically in the superior temporal gyrus, a region the analysis linked to auditory functions and overlapping with the somatomotor network.

No safety, tolerability, or adverse event data were reported for the fMRI procedures. The study's key limitations include its observational nature, the inferential process of functional decoding, and the lack of reported effect sizes or absolute participant numbers for specific findings. The analysis used cluster-level family-wise error correction to control for false positives.

For clinical practice, this meta-analysis provides a synthesized map of task-related brain activation differences in MCI and AD. The findings highlight distinct neural signatures but represent spatial associations from cross-sectional data. They do not establish causation, predict disease progression, or demonstrate utility for individual diagnosis or treatment monitoring.

Study Details

Study typeMeta analysis
EvidenceLevel 1
PublishedApr 2026
View Original Abstract ↓
Two decades of task-based fMRI studies have revealed atypical task-related activation and hypoactivation patterns in Alzheimer's disease (AD) and mild cognitive impairment (MCI), implicating the impaired cognitive processing observed in these neurocognitive disorders. The current coordinate-based meta-analysis provides an updated picture of the pathophysiological neurocognitive mechanisms implicated in MCI and AD, which better controls for false positive findings. To pool and summarise these findings, we conducted activation likelihood estimation (ALE) meta-analyses on 90 eligible studies (N = 2824) with cluster-level family-wise error correction to compare AD/MCI and healthy controls (HC) on fMRI activity during cognitive tasks across four different domains. ALE assesses whether there is a spatial convergence of activation among experiments. We then conducted meta-analytic functional decoding on the ALE meta-analysis results to infer the functional relevance of the significant clusters. Significant activation clusters, mostly overlapping with the dorsal attention and frontoparietal networks, were observed in MCI and HC when comparing them across memory tasks and all tasks, regardless of cognitive domain. Functional decoding analyses suggest these clusters are linked to spatial and phonological processing. Significant activation converged in the superior temporal gyrus in AD and overlapped with the somatomotor network. Functional decoding indicates it is related to auditory functions. Our findings illustrated the spatial convergence of aberrant task-related activation and hypoactivation in AD and MCI, highlighting the atypical neurocognitive processing across a broad range of tasks.
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