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Retrograde memory for public events in mild cognitive impairment and its relationship to anterograde memory and neuroanatomy.

ABSTRACT: The study characterized the status of retrograde amnesia (RA) in amnestic mild cognitive impairment (MCI).We measured RA, anterograde amnesia (AA), brain measures, apolipoprotein-E status (ApoE), and conversion to probable Alzheimer's disease (AD) across 3 years in 15 individuals with MCI. We compared the severity of amnesia and brain atrophy in MCI to a group of patients with limited damage to the hippocampus (H) or more extensive damage to the medial temporal lobe (MTL).The MCI group exhibited modest AA, together with severe RA, covering nearly 4 decades before their diagnosis. Compared with H-MTL patients, the temporal extent of RA was disproportionate to the severity of AA. The MCI group exhibited more modest AA and MTL atrophy than H-MTL patients, together with more severe RA and neocortical atrophy than H-MTL patients. The severity of AA corresponded to the integrity of MTL structures, whereas the severity of RA corresponded to the integrity of both MTL and neocortical structures. RA (but not AA, nor measures of cognitive status) was related to ApoE status and subsequent diagnosis of probable AD. RA was predicted by heritable risk for AD, in addition to the integrity of MTL and neocortical structures.Compared with H-MTL patients, the MCI group exhibited RA that was disproportionate to their AA and that was more severe than would be expected if their atrophy were limited primarily to the MTL. Heritable risk for AD, as well as the integrity of brain regions within and beyond the MTL, are important for understanding RA in MCI.

SUBMITTER: Smith CN

PROVIDER: S-EPMC4227913 | biostudies-literature | 2014 Nov

REPOSITORIES: biostudies-literature

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Retrograde memory for public events in mild cognitive impairment and its relationship to anterograde memory and neuroanatomy.

Smith Christine N CN

Neuropsychology 20140728 6

<h4>Objective</h4>The study characterized the status of retrograde amnesia (RA) in amnestic mild cognitive impairment (MCI).<h4>Method</h4>We measured RA, anterograde amnesia (AA), brain measures, apolipoprotein-E status (ApoE), and conversion to probable Alzheimer's disease (AD) across 3 years in 15 individuals with MCI. We compared the severity of amnesia and brain atrophy in MCI to a group of patients with limited damage to the hippocampus (H) or more extensive damage to the medial temporal l ...[more]

PMID: 25068664

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Project description: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).

Project description:The increased understanding that neuropathology begins decades before symptom onset, has led to the conceptualization and widespread utilization of Mild Cognitive Impairment (MCI) as an important transitional state between healthy aging and dementia. Further subcategorization to MCI subtype has led to more distinct prognoses and it is widely considered that amnestic and non-amnestic MCI (aMCI, naMCI) likely have distinct pathophysiologies. Yet, accurately classification remains contentious. Here, we differentiate hippocampal subfield volume between subtypes, diagnosed according to stringent clinical consensus criteria, where aMCI is characterized based on deficits in delayed recall (rather than encoding). We then identify memory performance correlates to subfield volume and associations with long-term cognitive performance and outcome. 3D T1-weighted structural MRI was acquired in 142 participants recruited from the Healthy Brain Aging (HBA) Clinic and diagnosed with aMCI (n = 38), naMCI (n = 84) or subjective memory complaints (SMC; n = 20). T1-weighted datasets were processed with the cortical and hippocampal subfield processing streams in FreeSurfer (v6.0). Subfield volumes, and associations with baseline and longitudinal objective memory scores were then examined. Subfield volumes were found to differentiate clinical profiles: subiculum, CA1, CA4 and dentate gyrus volumes were significantly reduced in aMCI compared to both naMCI and SMC. CA1 subfield volume was shown to predict concurrent memory performance in aMCI, while dentate gyrus volume significantly predicted longitudinal verbal learning and memory decline in the entire cohort. Our findings demonstrate that using a more stringent diagnostic approach to characterizing aMCI is well justified, as delayed recall deficits are strongly linked to underlying volumetric subfield reductions in CA1, CA4 and the dentate gyrus, subfields known to be associated with mnemonic processes. Further research is now warranted to replicate these findings in other MCI samples.

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Retrograde memory for public events in mild cognitive impairment and its relationship to anterograde memory and neuroanatomy.

Publications

Retrograde memory for public events in mild cognitive impairment and its relationship to anterograde memory and neuroanatomy.

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