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Functional Neural Correlates of Anosognosia in Mild Cognitive Impairment and Alzheimer's Disease: a Systematic Review.

ABSTRACT: Functional neuroimaging techniques (i.e. single photon emission computed tomography, positron emission tomography, and functional magnetic resonance imaging) have been used to assess the neural correlates of anosognosia in mild cognitive impairment (MCI) and Alzheimer's disease (AD). A systematic review of this literature was performed, following the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement, on PubMed, EMBASE, and PsycINFO databases. Twenty-five articles met all inclusion criteria. Specifically, four brain connectivity and 21 brain perfusion, metabolism, and activation articles. Anosognosia is associated in MCI with frontal lobe and cortical midline regional dysfunction (reduced perfusion and activation), and with reduced parietotemporal metabolism. Reduced within and between network connectivity is observed in the default mode network regions of AD patients with anosognosia compared to AD patients without anosognosia and controls. During initial stages of cognitive decline in anosognosia, reduced indirect neural activity (i.e. perfusion, metabolism, and activation) is associated with the cortical midline regions, followed by the parietotemporal structures in later stages and culminating in frontotemporal dysfunction. Although the current evidence suggests differences in activation between AD or MCI patients with anosognosia and healthy controls, more evidence is needed exploring the differences between MCI and AD patients with and without anosognosia using resting state and task related paradigms.

SUBMITTER: Mondragon JD

PROVIDER: S-EPMC6560017 | biostudies-literature | 2019 Jun

REPOSITORIES: biostudies-literature

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Functional Neural Correlates of Anosognosia in Mild Cognitive Impairment and Alzheimer's Disease: a Systematic Review.

Mondragón Jaime D JD Maurits Natasha M NM De Deyn Peter P PP

Neuropsychology review 20190603 2

Functional neuroimaging techniques (i.e. single photon emission computed tomography, positron emission tomography, and functional magnetic resonance imaging) have been used to assess the neural correlates of anosognosia in mild cognitive impairment (MCI) and Alzheimer's disease (AD). A systematic review of this literature was performed, following the Preferred Reporting Items for Systematic Reviews and Meta Analyses statement, on PubMed, EMBASE, and PsycINFO databases. Twenty-five articles met a ...[more]

PMID: 31161466

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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:IntroductionThe incidence of Alzheimer's disease (AD) is increasing rapidly, causing a growing burden to health and economic worldwide. Several clinical trials in the past decade failed to find solutions, and there remains a lack of an effective treatment. The evidence suggests that early intervention for neurodegeneration would likely be effective in preventing cognitive decline. Cognitive decline in AD occurs continuously over a long period; however, there remains a lack of simple, rapid and accurate approach for diagnosis of amnestic mild cognitive impairment or subjective cognitive decline due to underlying Alzheimer's pathology. Resting-state functional MRI (rs-fMRI) determines the functional activities of the human brain non-invasively. The amplitude of low-frequency fluctuation (ALFF), fractional ALFF (fALFF) and regional homogeneity (ReHo) are rs-fMRI indicators with high repeatability. They have been studied as early diagnostic imaging markers for other diseases and may be promising markers also for AD.Methods and analysisThe following electronic literature databases will be searched from inception to December 2021: Medline-Ovid, Medline-PubMed, EMBase-Ovid, Cochrane Central and ClinicalTrials.gov. Two independent reviewers will select studies with eligible criteria, extract data and assess the quality of the original studies with our quality assessment tool individually. Missing data will be requested by sending emails to the corresponding authors. Brain regions will be presented for ALFF/fALFF and ReHo by performing activation likelihood estimation with the Seed-based d Mapping-Permutation of subject images V.6.21 software. Meta-regression will be performed to determine the potential brain regions that may strongly correlate with cognitive decline progression. Subgroup analysis, funnel plot, Egger's test and sensitivity analysis will be conducted to detect and explain potential heterogeneity.Ethics and disseminationThis study does not require formal ethical approval. The findings will be submitted to a peer-review journal.Prospero registration numberCRD42021229009.

Dataset Information

Functional Neural Correlates of Anosognosia in Mild Cognitive Impairment and Alzheimer's Disease: a Systematic Review.

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Functional Neural Correlates of Anosognosia in Mild Cognitive Impairment and Alzheimer's Disease: a Systematic Review.

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