Gray matter atrophy in patients with mild cognitive impairment/Alzheimer's disease over the course of developing delusions

Fischer, Corinne E.; Ting, Windsor Kwan-Chun; Millikin, Colleen; Ismail, Zahinoor; Schweizer, Tom A.

doi:10.1002/gps.4291

Cited by 35 publications

(29 citation statements)

References 26 publications

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“…Few longitudinal neuroimaging studies have investigated neural correlates of psychosis in AD. A voxel‐based morphometry (VBM) study, which investigated alterations in the grey matter volume in mild cognitive impairment (MCI) and AD patients both before and after the onset of delusions, detected significant reductions in grey matter volumes in the left posterior hemisphere (including cuneus and precuneus) and the cerebellum . Recently, Qian et al have reported a greater rate of atrophy in fronto temporal regions in AD patients with delusions .…”

Section: Introductionmentioning

confidence: 99%

Psychosis of Alzheimer's disease: Neuropsychological and neuroimaging longitudinal study

D'Antonio

Vita

Zazzaro

et al. 2019

Int J Geriat Psychiatry

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Objectives Psychosis of Alzheimer's disease (AD) may represent a distinct disease phenotype; however, neuropsychological profile and neural basis linked to this phenotype have not yet been clarified. In this study, we aimed at detecting whether impairment in specific cognitive domains predicts the onset of psychosis in AD patients and what grey matter alterations, their location, and the rate of atrophy are associated with psychosis of AD. Methods Longitudinal neuropsychological data from AD patients with and without psychosis were analysed to determine whether the neuropsychological profile can predict the onset of psychosis. A voxel‐based morphometry (VBM) on longitudinal T1‐weighted images was used to explore differences in grey matter volume and in the rate of atrophy between groups. Results Noncognitive domain predicted the psychosis onset. However, AD patients with psychosis exhibited greater atrophy in the right anterior‐inferior temporal lobe, including the fusiform gyrus (cluster‐p‐family‐wise error [pfwe] < 0.05; peak‐p uncorrected [pUNC] < 0.001) as well as greater rate of atrophy in the right insula than nonpsychotic patients (cluster‐pFWE = 0.075; peak‐pUNC < 0.001). The anterior‐inferior temporal lobe is part of the ventral visual stream, and the insula plays a key role in the salience network. Conclusions This finding suggests that damage in these areas underpins an impairment in the visual processing of the objects and an impairment in the attribution of salience to the misperceived stimuli, which in turn leads to the onset of psychosis. These findings tie in well with the neuropsychological model of psychosis, according to which the simultaneous presence of two factors, namely misperception and misattribution, underlies psychosis in dementia.

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Section: Introductionmentioning

confidence: 99%

Psychosis of Alzheimer's disease: Neuropsychological and neuroimaging longitudinal study

D'Antonio

Vita

Zazzaro

et al. 2019

Int J Geriat Psychiatry

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“…Our group also looked at this question with respect to delusions and found cross-sectionally grey matter volume loss increased in the right-frontal-temporal region [22]. We also examined patients longitudinally and found atrophy more pronounced in regions corresponding to the default mode network and cerebellum [23]. As none of the regions identified to date correspond to areas of atrophy in AD, combined they suggest a different mechanism may underlie the development of delusions in AD.…”

Section: Introductionmentioning

confidence: 99%

Lewy Bodies, Vascular Risk Factors, and Subcortical Arteriosclerotic Leukoencephalopathy, but not Alzheimer Pathology, are Associated with Development of Psychosis in Alzheimer’s Disease

Fischer

Qian

Schweizer

et al. 2016

JAD

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Background The neuropathological correlates of psychosis in Alzheimer’s disease (AD) is unclear, with some studies reporting a correlation between psychosis and increased AD pathology while others have found no association. Objective To determine the demographic, clinical, and neuropathological features associated with psychotic symptoms in clinically attributed and neuropathologically proven AD. Method We separately reviewed two overlapping groups of clinically diagnosed (cAD) AD patients with neuropathology data and neuropathologically definite (npAD) cases (regardless of clinical diagnosis) from the NACC database, and explored the relationships between psychosis and clinical variables, neuropathologic correlates, and vascular risk factors. Delusions and hallucinations, defined according to the NPI-Q, were analyzed separately. Results 1,073 subjects in the database fulfilled our criteria (890 cAD and 728 npAD patients). 34% of cAD and 37% of npAD had psychotic symptoms during their illness. Hallucinations were associated with greater cognitive and functional impairments on the MMSE and CDR, while delusional patients showed less impairment on CDR, consistent across cAD and npAD groups. Burden of AD pathology appears to relate to presence of psychotic symptoms in the clinical AD group, but this result is not confirmed in the neuropathologically confirmed group suggesting the findings in the clinical group were due to misdiagnosis of AD. Lewy body pathology, subcortical arteriosclerotic leukoencephalopathy, and vascular risk factors, including a history of hypertension and diabetes, were associated with the development of psychosis. Conclusions Vascular and Lewy body pathologies and vascular risk factors are important modifiers of the risk of psychosis in AD.

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“…Analysing patients more than one year (and up to three years) before conversion, 2 VBM studies found no changes in the frontal lobe. 43 , 46 The findings for GM loss in MCI and AD patients are shown in Table 1 .…”

Section: Resultsmentioning

confidence: 99%

Voxel-based morphometry in Alzheimers disease and mild cognitive impairment: Systematic review of studies addressing the frontal lobe

Ribeiro

Filho

2016

Dement. neuropsychol.

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Voxel-based morphometry (VBM) is a useful approach for investigating neurostructural brain changes in dementia. We systematically reviewed VBM studies of Alzheimer's disease (AD) and mild cognitive impairment (MCI), specifically focusing on grey matter (GM) atrophy in the frontal lobe. Methods: Two searches were performed on the Pubmed database. A set of exclusion criteria was applied to ensure the selection of only VBM studies that directly investigated GM volume abnormalities in AD and/or MCI patients compared to cognitively normal controls. Results: From a total of 46 selected articles, 35 VBM studies reported GM volume reductions in the frontal lobe. The frontal subregions, where most of the volume reductions were reported, included the inferior, superior and middle frontal gyri, as well as the anterior cingulate gyrus. We also found studies in which reduced frontal GM was detected in MCI patients who converted to AD. In a minority of studies, correlations between frontal GM volumes and behavioural changes or cognitive deficits in AD patients were investigated, with variable findings. Conclusion: Results of VBM studies indicate that the frontal lobe should be regarded as an important brain area when investigating GM volume deficits in association with AD. Frontal GM loss might not be a feature specific to late AD only. Future VBM studies involving large AD samples are warranted to further investigate correlations between frontal volume deficits and both cognitive impairment and neuropsychiatric symptoms.

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Gray matter atrophy in patients with mild cognitive impairment/Alzheimer's disease over the course of developing delusions

Cited by 35 publications

References 26 publications

Psychosis of Alzheimer's disease: Neuropsychological and neuroimaging longitudinal study

Psychosis of Alzheimer's disease: Neuropsychological and neuroimaging longitudinal study

Lewy Bodies, Vascular Risk Factors, and Subcortical Arteriosclerotic Leukoencephalopathy, but not Alzheimer Pathology, are Associated with Development of Psychosis in Alzheimer’s Disease

Voxel-based morphometry in Alzheimers disease and mild cognitive impairment: Systematic review of studies addressing the frontal lobe

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