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.
Highlights
IntroductionThe incidence and prevalence of anosognosia of memory deficits has a large variability across dementia populations
The conceptualization of Bunawareness dysfunction^ by Gabriel Anton and Arnold Pick in 1882 focused on the awareness of illness in the mentally sick, thereby marking the start of the contemporary era of the neuropsychological study of Electronic supplementary material The online version of this article contains supplementary material, which is available to authorized users.The cognitive decline continuum in Alzheimer’s disease can be divided into three stages, a preclinical, a prodromal and a clinical (Sperling et al, 2011)
While brain perfusion Single photon emission computed tomography (SPECT) studies primarily identify anosognosia in Alzheimer’s disease (AD) and amnestic mild cognitive impairment (MCI) as a frontal lobe dysfunction, the18F fluorodeoxyglucose positron emission tomography (PET) studies reviewed above show involvement of the cortical midline structures (Gerretsen et al, 2017; Nobili et al, 2010; Salmon et al, 2006; Therriault et al, 2018; Vannini et al, 2017) in the first stages of AD and dysfunction of the frontal lobe in later stages (Harwood et al, 2005; Jedidi et al, 2014; Sultzer et al, 2014)
Summary
The incidence and prevalence of anosognosia of memory deficits has a large variability across dementia populations. The lack of a consensus in the diagnosis of anosognosia for memory deficits, as reflected by a large number of anosognosia screening instruments, contributes to the lack of specificity in the diagnosis and to the wide range in the prevalence of anosognosia in dementia. Patients with mild or moderate AD have a reported incidence between 21.0 and 38.3% and a prevalence between 24.2 and 71.0% for anosognosia (Starkstein, Brockman, Bruce, & Petracca, 2010; Castrillo-Sanz et al, 2016; Turró-Garriga et al, 2016). Cross-cultural assessment of the differences in unawareness of memory deficits in a large community-based study reports regional differences in the frequency of anosognosia, from 81.2% in India to 72.0% in Latin America and 63.5% in China (Mograbi et al, 2012). Clinical data associate anosognosia to diverse dementias, and vice versa, clinical pathological studies suggest that dementia-related pathologies account for most cases of late-life anosognosia (Wilson et al, 2016)
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