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What are the neural correlates of meta-cognition and anosognosia in Alzheimer's disease? A systematic review.

ABSTRACT: Awareness of one's own cognitive processes (metacognition) or of one's own illness or deficits (anosognosia) can be impaired in people with Alzheimer's disease (AD). The neural correlates of anosognosia within AD remain inconclusive. Understanding anosognosia is of importance because of its impact on carer burden and increased institutionalization. A systematic review of structural and functional neuroimaging studies was conducted to identify specific brain regions associated with anosognosia within AD. Thirty-two studies were included in the systematic review. Reduced gray matter density, cerebral blood flow, and hypometabolism in 8 key regions were significantly associated with increased anosognosia scores in people with AD. The most frequently associated regions were the inferior frontal gyrus, anterior cingulate cortex, and medial temporal lobe. Other key regions include the superior frontal gyrus, medial frontal gyrus, orbitofrontal cortex, posterior cingulate cortex, and the insula. Identifying brain regions associated with anosognosia can aid understanding and identification of anosognosia in people with AD and potentially facilitate improvements in care.

SUBMITTER: Hallam B

PROVIDER: S-EPMC7903321 | biostudies-literature | 2020 Oct

REPOSITORIES: biostudies-literature

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What are the neural correlates of meta-cognition and anosognosia in Alzheimer's disease? A systematic review.

Hallam Brendan B Chan Justin J Gonzalez Costafreda Sergi S Bhome Rohan R Huntley Jonathan J

Neurobiology of aging 20200618

Awareness of one's own cognitive processes (metacognition) or of one's own illness or deficits (anosognosia) can be impaired in people with Alzheimer's disease (AD). The neural correlates of anosognosia within AD remain inconclusive. Understanding anosognosia is of importance because of its impact on carer burden and increased institutionalization. A systematic review of structural and functional neuroimaging studies was conducted to identify specific brain regions associated with anosognosia wi ...[more]

PMID: 32679396

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Project description:Alzheimer's disease is the most common form of dementia. Its prodromal stage amnestic mild cognitive impairment is characterized by deficits of anterograde episodic memory. The development of standardized imaging inclusion criteria has to be regarded as a prerequisite for future diagnostic systems. Moreover, successful treatment requires isolating imaging markers predicting the disease. Accordingly, we conducted a systematic and quantitative meta-analysis to reveal the prototypical neural correlates of Alzheimer's disease and its prodromal stage. To prevent any a priori assumptions and enable a data-driven approach only studies applying quantitative automated whole brain analysis were included. Finally, 40 studies were identified involving 1351 patients and 1097 healthy control subjects reporting either atrophy or decreases in glucose utilization and perfusion. The currently most sophisticated and best-validated of coordinate-based voxel-wise meta-analyses was applied (anatomical likelihood estimates). The meta-analysis reveals that early Alzheimer's disease affects structurally the (trans-)entorhinal and hippocampal regions, functionally the inferior parietal lobules and precuneus. Results further may suggest that atrophy in the (trans-)entorhinal area/hippocampus and hypometabolism/hypoperfusion in the inferior parietal lobules predicts most reliably the progression from amnestic mild cognitive impairment to Alzheimer's disease, whereas changes in the posterior cingulate cortex and precuneus are unspecific. Fully developed Alzheimer's disease involved additionally a frontomedian-thalamic network. In conclusion, the meta-analysis characterizes the prototypical neural substrates of Alzheimer's disease and its prodromal stage amnestic mild cognitive impairment. By isolating predictive markers it enables successful treatment strategies in the future and contributes to standardized imaging inclusion criteria for Alzheimer's disease as suggested for future diagnostic systems.

Project description:BackgroundWe performed an updated meta-analysis of randomized placebo-controlled trials testing memantine monotherapy for patients with Alzheimer's disease (AD).MethodsThe meta-analysis included randomized controlled trials of memantine monotherapy for AD, omitting those in which patients were also administered a cholinesterase inhibitor. Cognitive function, activities of daily living, behavioral disturbances, global function, stage of dementia, drug discontinuation rate, and individual side effects were compared between memantine monotherapy and placebo groups. The primary outcomes were cognitive function and behavioral disturbances; the others were secondary outcomes.ResultsNine studies including 2433 patients that met the study's inclusion criteria were identified. Memantine monotherapy significantly improved cognitive function [standardized mean difference (SMD)=-0.27, 95% confidence interval (CI)=-0.39 to -0.14, p=0.0001], behavioral disturbances (SMD=-0.12, 95% CI=-0.22 to -0.01, p=0.03), activities of daily living (SMD=-0.09, 95% CI=-0.19 to -0.00, p=0.05), global function assessment (SMD=-0.18, 95% CI=-0.27 to -0.09, p=0.0001), and stage of dementia (SMD=-0.23, 95% CI=-0.33 to -0.12, p=0.0001) scores. Memantine was superior to placebo in terms of discontinuation because of inefficacy [risk ratio (RR)=0.36, 95% CI=0.17¬ to 0.74, p=0.006, number needed to harm (NNH)=non significant]. Moreover, memantine was associated with less agitation compared with placebo (RR=0.68, 95% CI=0.49 to 0.94, p=0.02, NNH=non significant). There were no significant differences in the rate of discontinuation because of all causes, all adverse events, and individual side effects other than agitation between the memantine monotherapy and placebo groups.ConclusionsMemantine monotherapy improved cognition, behavior, activities of daily living, global function, and stage of dementia and was well-tolerated by AD patients. However, the effect size in terms of efficacy outcomes was small and thus there is limited evidence of clinical benefit.

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Dataset Information

What are the neural correlates of meta-cognition and anosognosia in Alzheimer's disease? A systematic review.

Publications

What are the neural correlates of meta-cognition and anosognosia in Alzheimer's disease? A systematic review.

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