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.

Keywords: Alzheimer; Anosognosia; Connectivity; Metabolism; Mild cognitive impairment; Perfusion.

Fig. 1

Preferred Reporting Items for Systematic Reviews and Meta-Analyses patient selection flowchart. FTD: frontotemporal demetia

Fig. 2

Graphical representation of the neural correlates of anosognosia, case-control studies, in mild cognitive impairment patients based on data from: Hanyu et al., , Nobili et al., , Therriault et al., , Vannini et al., . Hypoperfusion in the bilateral lateral (LFL) and medial frontal (MFL) lobes, the bilateral anterior cingulate cortex (ACC) and cingulate gyri (CG), and the left inferior parietal region (IPL). Hypometabolism of the posterior cingulate cortex, precuneus (Pre), right hippocampus (Hip), bilateral temporal cortex (MTC), left inferior parietal lobule (IPL), the left angular gyrus (AG), and the left superior temporal gyrus (STG). Reduced functional within-network connectivity between precuneus (Pre) and bilateral inferior parietal lobes (IPL), left posterior cingulate cortex, left orbitofrontal cortex (OFC). Reduced functional connectivity between right hippocampus (Hip) and left medial temporal cortex (MTC) and right fusiform gyrus (not shown). a lateral view, b axial view, c sagittal view, and d coronal view. Hypoperfusion in red, hypometabolism in orange, reduced within-network connectivity in blue, and reduced between network connectivity in purple

Fig. 3

Graphical representation of the neural correlates of unawareness of memory deficits in mild cognitive impairment based on data from: Nobili et al., , Ries et al., , Vogel et al., . Hypoperfusion in the right inferior frontal gyrus (IFG). Hypometabolism in the left precuneus (Pre), left inferior parietal lobe (IPL) and left superior occipital gyrus (SOG), right inferior parietal lobe (IPL), right angular gyrus (AG) and right middle temporal gyrus (MTG). Hypoactivation in the bilateral medial prefrontal (mPFC) and posterior cingulate cortices (PCC). a lateral view, b axial view, c sagittal view, and d coronal view. Hypoperfusion in red, hypometabolism in orange, and hypoactivation in green

Fig. 4

Graphical representation of the neural correlates of anosognosia, case-control studies, in mild to moderate AD patients based on data from: Amanzio et al., , Berlingeri et al., , Gerretsen et al., , Sedaghat et al., , Starkstein et al., , Tagai et al., . Hypoperfusion in the right frontal lobe (FL, frontal inferior, frontal superior and prefrontal cortex), the right inferior parietal (IPL), bilateral medial temporal cortex (MTC), and right prefrontal cortex. Hyperperfusion of left temporoparietal junction (TPJ). Hypometabolism in posterior cingulate cortex and right angular gyrus (AG). Hypoactivation in the right postcentral gyrus (PCG), right parietotemporal and parietooccipital junction (POJ) and the left temporal gyrus (TG), striatum (Str) and cerebellum (Cer). Reduced functional connectivity within the default mode network (comprised of the lateral temporal cortex, LTC, the hippocampus, Hip, and the insula, IC), and reduced connectivity between the hippocampus and insular cortex. a lateral view, b axial view, c sagittal view, and d coronal view. Hypoperfusion in red, hyperperfusion in pink, hypoactivation in green, reduced within-network connectivity in blue, and reduced between network connectivity in purple

Fig. 5

Graphical representation of the neural correlates of unawareness of memory deficits in mild to moderate AD based on data from: Derouesné et al., , Harwood et al., , Jedidi et al., , Mimura & Yano, , Perrotin et al., , Reed et al., , Ries et al., , Ruby et al., , Salmon et al., , Shibata et al., , Sultzer et al., , Zamboni et al., . Hypoperfusion of bilateral frontal regions (FL, medial frontal, medial prefrontal cortex, mPFC, and orbitofrontal cortex, OFC), the right dorsolateral frontal lobe (dLFL), the right precuneus (Pre) and right inferior frontal gyrus (IFG). Hypometabolism of the bilateral medial prefrontal cortex, bilateral orbitofrontal cortex and posterior cingulate cortices, the right lateral frontal cortex (LFC), the right parahippocampal cortex (PhC), the right gyrus rectus (GR), the right middle temporal cortex (MTC), left superior frontal sulcus (SFS), left dorsomedial prefrontal cortex. Hypoactivation of the bilateral dorsomedial prefrontal cortex, bilateral medial prefrontal cortex and bilateral anterior temporal cortices (ATC). Attenuated within-network functional connectivity in the medial prefrontal cortex and proximal areas [bilateral dorsolateral prefrontal cortex (dLFL), bilateral caudate (Cau), and left posterior hippocampus (Hip)]. Hyperactivation of intraparietal sulcus (IPS). Reduced between network connectivity among the orbitofrontal cortex and the middle temporal cortex, and between the posterior cingulate cortex and the middle temporal cortex. a lateral view, b axial view, c sagittal view, and d coronal view. Hypoperfusion in red, hypometabolism in orange, hypoactivation in green, hyperactivation in pink, reduced within-network connectivity in blue, and reduced between network connectivity in purple