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Cognition and morphological brain changes in Charles Bonnet syndrome

Russell, Gregor

[Thesis]. Manchester, UK: The University of Manchester; 2014.

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Abstract

This thesis is entitled ‘Cognition and morphological brain changes in Charles Bonnet syndrome’. It has been prepared by Dr Gregor Russell, and has been submitted in pursuance of the degree of Doctor of Medicine at The University of Manchester.Charles Bonnet syndrome (CBS) is defined as complex persistent visual hallucinations in the absence of mental disorder. It is associated with advanced age and poor vision. It is common, with prevalence estimates of up to 63% among older people with significant visual impairment. CBS would not be diagnosed in the presence of dementia, but its relationship to milder cognitive impairment is unclear. The few studies that have examined this are underpowered and provide contradictory results. There are 16 case reports of dementia emerging in people with a diagnosis of CBS. These cases raise the possibility of an association between impaired insight at diagnosis of CBS and the subsequent development of dementia. This thesis reports the findings of a prospective cohort study which describes changes in cognitive functioning over one year in patients with CBS and age-matched controls. Participants were recruited from low vision and glaucoma assessment clinics. A clinical assessment was carried out by an old age psychiatrist, and participants had a detailed assessment of visual functioning. This thesis also describes the findings of the first study to use voxel-based morphometry (VBM) to investigate changes in volume of grey and white matter in CBS. Participants were recruited from the same clinics as the cohort study, and underwent MRI scanning on a 1.5T scanner, to a protocol designed to produce 1mm3 voxels. Twelve participants with CBS and ten controls were followed up. Two people in the CBS group developed dementia, while none did in the control group. The CBS group showed a mean change in the score on the Addenbrooke’s cognitive examination (ACE-R) of -3.7 points, compared to a change of +1.4 in the control group. This difference was not statistically significant. The CBS participants performed worse on the verbal fluency item of the ACE-R, a difference which was statistically significant. The VBM analysis was conducted on 11 CBS participants and 11 controls. The CBS group showed an increase in grey matter volume in the right cerebellar hemisphere. This difference retained significance after family-wise error correction, non-stationary correction, and ANCOVA to control for the effects of possible confounders.As far as the author is aware, these are the most methodologically robust studies to date to have investigated cognition and morphological brain changes in CBS. The findings of the cohort study were inconclusive. However, the two cases of dementia in CBS patients add weight to the suspicion that this is a clinically important outcome in the condition, and the finding of abnormalities in frontal lobe testing in participants with CBS fits with a theoretical model of visual hallucination generation. Moreover, this type of research appears to be acceptable to a frail and visually disabled population, and studies powered to investigate this issue more fully would be feasible. The VBM findings report the presence of underlying structural brain abnormalities in CBS, in a region not usually associated with visual hallucinations. Possible links with Lewy body dementia, and implications for theories of visual hallucinations, are discussed.

Layman's Abstract

This thesis is entitled ‘Cognition and morphological brain changes in Charles Bonnet syndrome’. It has been prepared by Dr Gregor Russell, and has been submitted in pursuance of the degree of Doctor of Medicine at The University of Manchester.Charles Bonnet syndrome (CBS) is a common condition among older people with poor eyesight. People with this condition experience visions of people and objects which are not actually there. In CBS these visions are not caused by mental health problems. People with dementia can also experience visions, and the relationship between these conditions is uncertain. A diagnosis of dementia would exclude CBS, but milder problems with memory would probably not be picked up by eye specialists who see most cases of CBS. This thesis reports the findings of two linked studies. In the first, a group of patients with CBS, and a group of people of similar age and visual functioning, had their memory tested by a psychiatrist and their vision measured by an optometrist. They were then followed up for a year and the tests were repeated. The number of people who developed dementia in each group was counted. In the second study, a group of people with CBS, and a comparison group, underwent MRI scans of their brain. The scans of each group were combined and then the two groups were compared to see if any regions of the brain were different in people with CBS.The first study found that two patients with CBS did develop dementia, while none of the comparison group did. The CBS group also did worse on memory tests after a year, while the comparison group did a little better. However, because the study was small, these results could have happened by chance. The people with CBS did worse on the part of the test that examines the frontal lobe of the brain; this difference was unlikely to have happened by chance. The MRI scans showed the brains for patients with CBS were different, with more grey matter in a part of the brain called the cerebellum. It is unlikely that this difference was just chance.The most important finding of the first study is that this sort of research is acceptable to the participants, despite their age and health problems. It is therefore feasible to consider a larger, more powerful study that could determine the nature of the relationship between CBS and dementia. As this would be important in the planning of services for the timely diagnosis of dementia, this would be a worthwhile study to conduct. It also suggested that the frontal lobe may be abnormal in CBS, and this may be partly responsible for why some people with poor eyesight get CBS while others do not; this is a very tentative finding but worth looking at further. The MRI study reports that the brains of people with CBS are different from those without it. The area of the brain affected is not usually thought of as related to visual hallucinations, but it is involved in the control of rapid eye movements and has been shown to be abnormal in a form of dementia where visions commonly occur. This finding could have implications for theories of how visual hallucinations develop, and which parts of the brain are involved in producing them.

Keyword(s)

Alzheimer's disease; Charles Bonnet syndrome; Lewy body dementia; cognitive impairment; magnetic resonance imaging; visual hallucinations; voxel-based morphometry

Bibliographic metadata

Type of resource:

text

Content type:

Administered thesis

Form of thesis:

Traditional

Type of submission:

Doctoral level ETD - final

Thesis title:

Cognition and morphological brain changes in Charles Bonnet syndrome

Degree programme:

MD Medicine (BBMH) 48

Publication date:

2014-09-19T20:37:39

Institution:

The University of Manchester

Location:

Manchester, UK

Total pages:

454

Abstract:

Layman's abstract:

This thesis is entitled ‘Cognition and morphological brain changes in Charles Bonnet syndrome’. It has been prepared by Dr Gregor Russell, and has been submitted in pursuance of the degree of Doctor of Medicine at The University of Manchester.Charles Bonnet syndrome (CBS) is a common condition among older people with poor eyesight. People with this condition experience visions of people and objects which are not actually there. In CBS these visions are not caused by mental health problems. People with dementia can also experience visions, and the relationship between these conditions is uncertain. A diagnosis of dementia would exclude CBS, but milder problems with memory would probably not be picked up by eye specialists who see most cases of CBS. This thesis reports the findings of two linked studies. In the first, a group of patients with CBS, and a group of people of similar age and visual functioning, had their memory tested by a psychiatrist and their vision measured by an optometrist. They were then followed up for a year and the tests were repeated. The number of people who developed dementia in each group was counted. In the second study, a group of people with CBS, and a comparison group, underwent MRI scans of their brain. The scans of each group were combined and then the two groups were compared to see if any regions of the brain were different in people with CBS.The first study found that two patients with CBS did develop dementia, while none of the comparison group did. The CBS group also did worse on memory tests after a year, while the comparison group did a little better. However, because the study was small, these results could have happened by chance. The people with CBS did worse on the part of the test that examines the frontal lobe of the brain; this difference was unlikely to have happened by chance. The MRI scans showed the brains for patients with CBS were different, with more grey matter in a part of the brain called the cerebellum. It is unlikely that this difference was just chance.The most important finding of the first study is that this sort of research is acceptable to the participants, despite their age and health problems. It is therefore feasible to consider a larger, more powerful study that could determine the nature of the relationship between CBS and dementia. As this would be important in the planning of services for the timely diagnosis of dementia, this would be a worthwhile study to conduct. It also suggested that the frontal lobe may be abnormal in CBS, and this may be partly responsible for why some people with poor eyesight get CBS while others do not; this is a very tentative finding but worth looking at further. The MRI study reports that the brains of people with CBS are different from those without it. The area of the brain affected is not usually thought of as related to visual hallucinations, but it is involved in the control of rapid eye movements and has been shown to be abnormal in a form of dementia where visions commonly occur. This finding could have implications for theories of how visual hallucinations develop, and which parts of the brain are involved in producing them.

Keyword(s):