Trajectory of Unawareness of Memory Decline in Individuals With Autosomal Dominant Alzheimer Disease

Vannini, Patrizia; Hanseeuw, Bernard; Gatchel, Jennifer R.; Sikkes, Sietske A.M.; Alzate, Diana; Zuluaga, Yesica; Moreno, Sonia; Méndez, Luis; Baena, Ana; Lopera, Paula Ospina; Tirado, Victoria; Henao, Eliana; Acosta‐Baena, Natalia; Giraldo, Margarita; Lopera, Francisco; Quiroz, Yakeel T.

doi:10.1001/jamanetworkopen.2020.27472

Cited by 26 publications

(37 citation statements)

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“…Both the participants with low amyloid load and their study-partners reported more difficulties over time, resulting in stable ACD. A second longitudinal study (Vannini et al, 2020 ) selected 396 presenilin (PSEN1 E280A) variant carriers from the Colombia Alzheimer's Prevention Initiative Registry (Tariot et al, 2018 ), 59 of which were cognitively-impaired. ACD was measured as the subject-informant discrepancy on a memory complaint scale (Gatchel et al, 2020 ).…”

Section: Resultsmentioning

confidence: 99%

Awareness of Cognitive Decline in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis

Cacciamani

Houot

Gagliardi

et al. 2021

Front. Aging Neurosci.

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Background: Identifying a poor degree of awareness of cognitive decline (ACD) could represent an early indicator of Alzheimer's disease (AD).Objectives: (1) to understand whether there is evidence of poor ACD in the pre-dementia stages of AD; (2) to summarize the main findings obtained investigating ACD in AD; (3) to propose a conceptual framework.Data Sources: We searched Scopus, Pubmed, and the reference lists for studies published up to August 2020. Original research articles must report a measure of ACD and included individuals with AD dementia, or prodromal AD (or MCI), or being at risk for AD.Data Synthesis: All studies covering preclinical, prodromal, and AD dementia were systematically reviewed. We intended to perform a meta-analysis of empirical studies on preclinical AD or prodromal AD (or MCI), to compare ACD between clinical groups. Due to the paucity of literature on preclinical AD, meta-analysis was only possible for prodromal AD (or MCI) studies.Results: We systematically reviewed 283 articles, and conducted a meta-analysis of 18 articles on prodromal AD (or MCI), showing that ACD was not significantly different between patients with amnestic and non-amnestic MCI (SMD = 0.09, p = 0.574); ACD was significantly poorer in amnestic MCI (SMD = −0.56, p = 0.001) and mild AD (SMD = −1.39, p < 0.001) than in controls; ACD was also significantly poorer in mild AD than in amnestic MCI (SMD = −0.75, p < 0.001), as well as poorer than in non-amnestic MCI (SMD = −1.00, p < 0.001). We also discuss key findings on ACD in AD, such as its neural and cognitive correlates.Conclusions and Implications: We propose that patients may be complaining of their initial subtle cognitive changes, but ACD would soon start to decrease. The individual would show mild anosognosia in the MCI stage, and severe anosognosia in dementia. The evaluation of ACD (comparing self-report to cognitive scores or to informant-report) could be useful to guide the clinician toward a timely diagnosis, and in trials targeting early-stage AD.

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Section: Resultsmentioning

confidence: 99%

Awareness of Cognitive Decline in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis

Cacciamani

Houot

Gagliardi

et al. 2021

Front. Aging Neurosci.

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“…Although anosognosia is very common at the clinical stage of AD, recent studies have shown that awareness starts to change even before the AD dementia stage (Folstein et al, 1975;Cacciamani et al, 2017Cacciamani et al, , 2020. Previous research has shown that some individuals may demonstrate heightened awareness of subtle cognitive changes at the preclinical stage, with a subsequent decline of awareness as the individual moves along the AD trajectory (Vannini et al, 2017a(Vannini et al, , 2020Hanseeuw et al, 2020). Additionally, recent studies have suggested that loss of awareness may be present in the predementia stages of AD, e.g., in the prodromal (Perrotin et al, 2015;Vannini et al, 2017c;Edmonds et al, 2018;Munro et al, 2018;Therriault et al, 2018) and even preclinical stages (Folstein et al, 1975;Cacciamani et al, 2017;Vannini et al, 2017b).…”

Section: Introductionmentioning

confidence: 99%

Episodic Memory Impairment Mediates the Loss of Awareness in Mild Cognitive Impairment

Gagliardi

Vannini

2022

Front. Aging Neurosci.

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IntroductionLoss of awareness is a common symptom in Alzheimer's Disease (AD) and responsible for a significant loss of functional abilities. The mechanisms underlying loss of awareness in AD is unknown, although previous findings have implicated dysfunction of primary executive functioning (EF) or episodic memory (EM) to be the cause. Therefore, our main study objective was to explore the involvement of EF and EM dysfunction in amyloid-related loss of awareness across the clinical spectrum of AD.MethodsA total of 895 participants (362 clinically normal [CN], 422 people with mild cognitive impairment [MCI] and 111 with dementia) from the Alzheimer's Disease Neuroimaging Initiative were used for the analyses. A sub-analysis was performed in 202 participants who progressed in their clinical diagnosis from CN to MCI or MCI to dementia as well as dementia patients. Mediation models were used in each clinical group with awareness (assessed with the Everyday Cognitive function questionnaire) as a dependent variable to determine whether EF and/or EM would mediate the effect of amyloid on awareness. We also ran these analyses with subjective and informant complaints as dependent variables. Direct correlations between all variables were also performed.ResultsWe found evidence for a decline in awareness across the groups, with increased awareness observed in the CN group and decreased awareness observed in the MCI and dementia groups. Our results showed that EM, and not EF, partially mediated the relationship between amyloid and awareness such that greater amyloid and lower EM performance was associated with lower awareness. When analyzing each group separately, this finding was only observed in the MCI group and in the group containing progressors and dementia patients. When repeating the analyses for subjective and informant complaints separately, the results were replicated only for the informant's complaints.DiscussionOur results demonstrate that decline in EM and, to a lesser degree, EF, mediate the effect of amyloid on awareness. In line with previous studies demonstrating the development of anosognosia in the prodromal stage, our findings suggest that decreased awareness is the result of an inability for the participant to update his/her insight into his/her cognitive performance (i.e., demonstrating a petrified self).

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“…In fact, to date, three longitudinal studies have demonstrated that lack of awareness of memory impairment appears approximately 2 to 3 years before the clinical progression to AD diagnosis [ 24 ]. Of these studies, Wilson and colleagues [ 24 ] used the participant-objective discrepancy method, while Hanseeuw et al [ 5 ] and Vannini et al [ 25 ] used the participant-informant discrepancy. Despite these consistent findings, what is less clear is the mechanism underlying altered self-awareness across the AD spectrum (i.e., from the preclinical to the dementia stage), and especially any relationship between self-awareness and AD pathology.…”

Section: Introductionmentioning

confidence: 99%

Pathological correlates of impaired self-awareness of memory function in Alzheimer’s disease

et al. 2021

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Introduction Impaired self-awareness of memory function, a.k.a. anosognosia, is a common symptom in Alzheimer’s disease (AD); however, its pathological correlates remain unclear. Here, we investigated the impact of amyloid and tau on memory self-awareness. Methods Two hundred thirty-six clinically normal (N) and 102 impaired (I) participants from the ADNI cohort were included. Amyloid (global) and tau burden (in entorhinal and inferior temporal cortices) were assessed using positron emission tomography (PET). Self-awareness of memory was assessed using discrepancy indexes of subjective participant-informant ratings, as well as participant-objective scores of memory performance. Subjective and objective values were derived from the Everyday Cognition memory questionnaire and Logical Memory (delayed recall). Results Lower awareness (both methods) of memory function was associated with higher levels of pathology in the I group as compared to N. There was a significant effect of tauopathy, but not amyloidosis, on individual complaint, such that higher levels of tau associated with lower awareness. Discussion Impaired self-awareness appears progressively in the evolution of the disease related to AD biomarkers. Discordant subjective and objective measures may be important for clinical consideration.

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Trajectory of Unawareness of Memory Decline in Individuals With Autosomal Dominant Alzheimer Disease

Cited by 26 publications

References 59 publications

Awareness of Cognitive Decline in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis

Awareness of Cognitive Decline in Patients With Alzheimer's Disease: A Systematic Review and Meta-Analysis

Episodic Memory Impairment Mediates the Loss of Awareness in Mild Cognitive Impairment

Pathological correlates of impaired self-awareness of memory function in Alzheimer’s disease

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