Neuroanatomical Correlates of Unawareness of Memory Deficits in Early Alzheimer’s Disease

Department of Geriatric Medicine, Tokyo Medical University, Tokyo, Japan.
Dementia and Geriatric Cognitive Disorders (Impact Factor: 3.55). 02/2008; 25(4):347-53. DOI: 10.1159/000119594
Source: PubMed


To investigate neuroanatomical substrates of unawareness of memory deficits in patients with early Alzheimer's disease (AD).
We compared regional perfusion deficits between AD patients with awareness (n = 19) and unawareness (n = 19). SPECT data were analyzed by statistical brain imaging method.
Statistical maps demonstrated a more extensive and severe reduction in perfusion in the unaware group than in the aware group. Quantitative analysis demonstrated a significant difference between the groups in the right subcallosal, anterior cingulate and cingulate gyri and left orbital, subcallosal, and anterior cingulate gyri.
Functional damage to the inferior, medial and orbital frontal lobes as well as the anterior cingulate gyri may be associated with the lack of awareness in patients with early AD.

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    • "In fact, a number of studies have investigated the neuroanatomical underpinnings of anosognosia in AD, mostly stressing a relationship with hypometabolism or hypoperfusion in orbital, lateral and medial frontal cortex (Derousn e et al., 1999; Hanyu et al., 2008; Harwood et al., 2005; Reed et al., 1993; Salmon et al., 2006; Sedaghat et al., 2010), and temporal cortical regions (Ott, Noto, & Fogel, 1996; Salmon et al., 2006; Sedaghat et al., 2010). On the contrary, very few data are available for MCI. "
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    ABSTRACT: Background: Awareness of cognitive deficits may be reduced in mild cognitive impairment (MCI). This may have a detrimental effect on illness course and may be a predictor of subsequent conversion to AD. Although neuropsychological correlates have been widely investigated, no evidence of a neuroanatomical basis of the phenomenon has been reported yet. This study was aimed at investigating the neuroanatomical correlates of deficit awareness in amnestic MCI to determine whether they constitute risk factors for conversion to AD. Method: A sample of 36 first-diagnosis amnestic MCI patients were followed for five years. At the first diagnostic visit they were administered an extensive diagnostic and clinical procedure and the Memory Insight Questionnaire (MIQ), measuring a total index and four sub-indices, to investigate awareness of deficits in dementia; they also underwent a high resolution T1-weighted Magnetic Resonance Imaging (MRI) investigation. Grey matter brain volumes were analysed on a voxel-by-voxel basis using Statistical Parametric Mapping 8. Data of 10 converter patients (CONV) and those of 26 non converter patients (NOCONV) were analysed using multiple regression models. Results: At baseline, self-awareness of memory deficits was poorer in CONV compared to NOCONV. Furthermore, reduced awareness of cognitive deficits in CONV correlated with reduced grey matter volume of the anterior cingulate (memory deficit awareness), right pars triangularis of the inferior frontal cortex (memory deficit awareness) and cerebellar vermis (total awareness), whereas in NOCONV it correlated with reduced grey matter volume of left superior (total awareness) and middle (language deficit awareness) temporal areas. Further, at baseline self-awareness of memory deficits were poorer in CONV than in NOCONV. Conclusions: Defective awareness of cognitive deficits is underpinned by different mechanisms in CONV and NOCONV amnestic MCI patients. Our data support the hypothesis that poor awareness of cognitive deficit is a predictor of subsequent conversion to AD.
    Cortex 12/2014; 61:183-95. DOI:10.1016/j.cortex.2014.10.010 · 5.13 Impact Factor
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    • "These processes are crucial for cognitive control, that is, when competition takes place between stereotyped or random responses and efficient and context-suitable behaviors; in fact, the former tend to be inhibited, whereas the latter tend to be encouraged [47] [48]. Interestingly, the involvement of frontal areas in poor awareness in AD, particularly PFC [49], OFC [9], and ACC [50] is widely documented. Thus, our data suggest that anosognosia in mild AD could be considered an expression of the inability to suppress habitual or irrelevant behaviors, regardless of external feedback or actual situational context. "

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    • "Some studies demonstrate strong relationships between awareness and executive functioning [12] [19] [20] [27], with others reporting nonsignificant and trivial associations [19] [29]. Although clearly composite measures that rely on more basic cognitive functions, many summary scores from traditional tests of executive function are associated with the dorsolateral prefrontal circuit [37], and awareness has been associated with more midline [34] [35] [36] or orbitofrontal aspects of the prefrontal cortex [33]. Contradictory data on the clinical correlates of awareness is also due to the assumption that awareness is a unitary construct (see reviews by [4] [8]). "
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    ABSTRACT: Awareness in dementia is increasingly recognized not only as multifactorial, but also as domain specific. We demonstrate differential clinical correlates for awareness of daily function, awareness of memory, and the novel exploration of awareness of balance. Awareness of function was higher for participants with mild cognitive impairment (aMCI and non-aMCI) than for those with dementia (due to Alzheimer disease; AD and non-AD), whereas awareness of memory was higher for both non-aMCI and non-AD dementia patients than for those with aMCI or AD. Balance awareness did not differ based on diagnostic subgroup. Awareness of function was associated with instrumental activities of daily living and caregiver burden. In contrast, awareness of balance was associated with fall history, balance confidence, and instrumental activities of daily living. Clinical correlates of awareness of memory depended on diagnostic group: associations held with neuropsychological variables for non-AD dementia, but for patients with AD dementia, depression and instrumental activities of daily living were clinical correlates of memory awareness. Together, these data provide support for the hypothesis that awareness and dementia are not unitary and are, instead, modality specific.
    Journal of aging research 01/2014; 2014(1):674716. DOI:10.1155/2014/674716
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