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1.
J Alzheimers Dis ; 89(1): 51-66, 2022.
Article in English | MEDLINE | ID: mdl-35848020

ABSTRACT

BACKGROUND: Olfactory dysfunction is highly prevalent in dementia syndromes, including Alzheimer's disease (AD) and frontotemporal dementia (FTD). The structural integrity of the olfactory bulb (OB) is thought to play a critical role in odor detection and identification, but no MRI study has measured OB volume in FTD, or measured OB volume longitudinally in AD. OBJECTIVE: To measure OB volume in FTD and AD patients longitudinally using MRI. METHODS: This study measured OB volumes using MRI in patients diagnosed with behavioral-variant FTD (n = 55), semantic dementia (n = 34), progressive non-fluent aphasia (n = 30), AD (n = 50), and healthy age-matched controls (n = 55) at their first visit to a dementia research clinic ('baseline'). Imaging data in patients 12-months later were analyzed where available (n = 84) for longitudinal assessment. Volumes of subcortical and cortical olfactory regions ('olfactory network') were obtained via surface-based morphometry. RESULTS: Results revealed that in AD and FTD at baseline, OB volumes were similar to controls, whereas volumes of olfactory network regions were significantly reduced in all patient groups except in progressive non-fluent aphasia. Longitudinal data revealed that OB volume became significantly reduced (10-25% volume reduction) in all dementia groups with disease progression. CONCLUSION: Olfactory dysfunction is common in patients diagnosed with AD or FTD, but our results indicate that there is no detectable volume loss to the OBs upon first presentation to the clinic. Our findings indicate that the OBs become detectably atrophied later in the disease process. OB atrophy indicates the potential usefulness for OBs to be targeted in interventions to improve olfactory function.


Subject(s)
Alzheimer Disease , Aphasia , Frontotemporal Dementia , Olfaction Disorders , Alzheimer Disease/complications , Alzheimer Disease/diagnostic imaging , Alzheimer Disease/pathology , Atrophy/pathology , Frontotemporal Dementia/complications , Frontotemporal Dementia/diagnostic imaging , Frontotemporal Dementia/pathology , Humans , Magnetic Resonance Imaging , Olfaction Disorders/diagnostic imaging , Olfaction Disorders/etiology , Olfaction Disorders/pathology , Olfactory Bulb/diagnostic imaging , Olfactory Bulb/pathology
2.
Int J Geriatr Psychiatry ; 37(3)2022 Feb 08.
Article in English | MEDLINE | ID: mdl-35178786

ABSTRACT

OBJECTIVES: Abnormal beliefs and delusions have been reported in some people with dementia, however, the prevalence of delusions, and their neurocognitive basis has been underexplored. This study aimed to examine the presence, severity, content and neural correlates of delusions in a large, well-characterised cohort of dementia patients using a transdiagnostic, cross-sectional approach. METHODS: Four-hundred and eighty-seven people with dementia were recruited: 102 Alzheimer's disease, 136 behavioural-variant frontotemporal dementia, 154 primary progressive aphasia, 29 motor neurone disease, 46 corticobasal syndrome, 20 progressive supranuclear palsy. All patients underwent neuropsychological assessment and brain magnetic resonance imaging, and the Neuropsychiatric Inventory was conducted with an informant, by an experienced clinician. RESULTS: In our cohort, 48/487 patients (10.8%) had delusions. A diagnosis of behavioural-variant frontotemporal dementia (18.4%) and Alzheimer's disease (11.8%) were associated with increased risk of delusions. A positive gene mutation was observed in 11/27 people with delusions. Individuals with frequent delusions performed worse on the Addenbrooke's Cognitive Examination (p = 0.035), particularly on the orientation/attention (p = 0.022) and memory (p = 0.013) subtests. Voxel-based morphometry analyses found that increased delusional psychopathology was associated with reduced integrity of the right middle frontal gyrus, right planum temporale and left anterior temporal pole. CONCLUSION: Our results demonstrate that delusions are relatively common in dementia and uncover a unique cognitive and neural profile associated with the manifestation of delusions. Clinically, delusions may lead to delayed or misdiagnosis. Our results shed light on how to identify individuals at risk of neuropsychiatric features of dementia, a crucial first step to enable targeted symptom management.

3.
Cortex ; 120: 201-211, 2019 11.
Article in English | MEDLINE | ID: mdl-31325799

ABSTRACT

To track neural correlates of naming performance with disease progression, we estimated key areas affected in nonfluent/agrammatic (nfvPPA) and logopenic (lvPPA) primary progressive aphasia variants over time and changes in naming correlates over time. Twenty-nine non-semantic PPA participants (17 nfvPPA and 12 lvPPA) were selected based upon current diagnostic criteria and PiB-PET status and conducted a confrontation-naming task and a structural MRI. Linear mixed-effect models implemented in FreeSurfer were used for tracking cortical thickness and epicenters of atrophy over time. Using averaged cortical thickness of epicenters and naming performance as variables of interest, two sets of multivariate analyses were conducted to compare atrophy progression and naming correlates across groups. While all PPA participants demonstrated naming deterioration and progressive cortical thinning in the left temporal lobe and the left inferior frontal gyrus, the lvPPA cohort showed greater naming deterioration and thinning in the left posterior inferior parietal cortex over time than it did the nfvPPA cohort. The multivariate analyses confirmed a widespread cortical thinning in lvPPA over time, but a more rapid thinning in the right superior frontal gyrus of nfvPPA participants. Impaired naming correlated with common cortical regions in both groups. These regions included the left anterior superior temporal gyrus and the posterior middle temporal gyrus, which was primarily affected in lvPPA. Non-semantic PPA variants initially present with separate epicenters of atrophy and different spatial-temporal patterns of neurodegeneration over time, but the common involvement in key cortical regions of the left temporal lobe accounts for naming deterioration in both groups.


Subject(s)
Anomia/psychology , Aphasia, Primary Progressive/psychology , Aged , Anomia/diagnostic imaging , Aphasia, Primary Progressive/diagnostic imaging , Aphasia, Primary Progressive/pathology , Atrophy , Brain Mapping , Cerebral Cortex/diagnostic imaging , Cerebral Cortex/pathology , Cognition , Disease Progression , Female , Frontal Lobe/diagnostic imaging , Frontal Lobe/pathology , Humans , Linear Models , Magnetic Resonance Imaging , Male , Middle Aged , Neuropsychological Tests , Parietal Lobe/diagnostic imaging , Parietal Lobe/pathology , Semantics , Temporal Lobe/diagnostic imaging , Temporal Lobe/pathology
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