P4-587: REGIONAL BRAIN VOLUMES RELATION TO ALZHEIMER'S DISEASE PATHOLOGY AND NEUROPSYCHOLOGICAL EXAMINATION

Abstract Posterior cortical atrophy is a clinico-radiological syndrome characterized by progressive decline in visual processing and atrophy of posterior brain regions. With the majority of cases attributable to Alzheimer’s disease and recent evidence for genetic risk factors specifically related to posterior cortical atrophy, the syndrome can provide important insights into selective vulnerability and phenotypic diversity. The present study describes the first major longitudinal investigation of posterior cortical atrophy disease progression. Three hundred and sixty-one individuals (117 posterior cortical atrophy, 106 typical Alzheimer’s disease, 138 controls) fulfilling consensus criteria for posterior cortical atrophy-pure and typical Alzheimer’s disease were recruited from three centres in the UK, Spain and USA. Participants underwent up to six annual assessments involving MRI scans and neuropsychological testing. We constructed longitudinal trajectories of regional brain volumes within posterior cortical atrophy and typical Alzheimer’s disease using differential equation models. We compared and contrasted the order in which regional brain volumes become abnormal within posterior cortical atrophy and typical Alzheimer’s disease using event-based models. We also examined trajectories of cognitive decline and the order in which different cognitive tests show abnormality using the same models. Temporally aligned trajectories for eight regions of interest revealed distinct (P < 0.002) patterns of progression in posterior cortical atrophy and typical Alzheimer’s disease. Patients with posterior cortical atrophy showed early occipital and parietal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion leading to tissue loss of comparable extent later. Hippocampal, entorhinal and frontal regions underwent a lower rate of change and never approached the extent of posterior cortical involvement. Patients with typical Alzheimer’s disease showed early hippocampal atrophy, with subsequent higher rates of temporal atrophy and ventricular expansion. Cognitive models showed tests sensitive to visuospatial dysfunction declined earlier in posterior cortical atrophy than typical Alzheimer’s disease whilst tests sensitive to working memory impairment declined earlier in typical Alzheimer’s disease than posterior cortical atrophy. These findings indicate that posterior cortical atrophy and typical Alzheimer’s disease have distinct sites of onset and different profiles of spatial and temporal progression. The ordering of disease events both motivates investigation of biological factors underpinning phenotypic heterogeneity, and informs the selection of measures for clinical trials in posterior cortical atrophy.

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P3-402: Validated Dementia Risk Measure is Associated with Regional Brain Volumes: The ANU Alzheimer's Disease Risk Index (ANU-ADRI)

Alzheimer s & Dementia ◽

10.1016/j.jalz.2016.06.2068 ◽

2016 ◽

Vol 12 ◽

pp. P1005-P1005

Author(s):

Nicolas Cherbuin ◽

Marnie Shaw ◽

Perminder S. Sachdev ◽

Kaarin J. Anstey

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Risk ◽

Risk Measure ◽

Risk Index ◽

Brain Volumes ◽

Regional Brain ◽

Dementia Risk

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Executive deficits and regional brain metabolism in Alzheimer's disease

International Journal of Geriatric Psychiatry ◽

10.1002/gps.2452 ◽

2010 ◽

Vol 25 (11) ◽

pp. 1150-1158 ◽

Cited By ~ 28

Author(s):

Benjamin K. P. Woo ◽

Dylan G. Harwood ◽

Rebecca J. Melrose ◽

Mark A. Mandelkern ◽

Olivia M. Campa ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Metabolism ◽

Regional Brain ◽

Executive Deficits

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O2-04-05: Relationships between hippocampal microstructural alterations and regional brain metabolism in early Alzheimer's disease: A combined DTI-PET study

Alzheimer s & Dementia ◽

10.1016/j.jalz.2010.05.326 ◽

2010 ◽

Vol 6 ◽

pp. S104-S105

Author(s):

Andreas Fellgiebel ◽

Matthias Schreckenberger ◽

Matthias J. Müller ◽

Ingrid Schermuly ◽

Peter Stoeter ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Brain Metabolism ◽

Microstructural Alterations ◽

Regional Brain ◽

Early Alzheimer’S Disease

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Reported Hearing Loss in Alzheimer’s Disease Is Associated With Loss of Brainstem and Cerebellar Volume

Frontiers in Human Neuroscience ◽

10.3389/fnhum.2021.739754 ◽

2021 ◽

Vol 15 ◽

Author(s):

Daniel A. Llano ◽

Susanna S. Kwok ◽

Viswanath Devanarayan ◽

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Hearing Loss ◽

Normal Subjects ◽

Neural Substrates ◽

Epidemiological Studies ◽

Brain Regions ◽

Pathological State ◽

Brain Volumes ◽

The Relationship

Multiple epidemiological studies have revealed an association between presbycusis and Alzheimer’s Disease (AD). Unfortunately, the neurobiological underpinnings of this relationship are not clear. It is possible that the two disorders share a common, as yet unidentified, risk factor, or that hearing loss may independently accelerate AD pathology. Here, we examined the relationship between reported hearing loss and brain volumes in normal, mild cognitive impairment (MCI) and AD subjects using a publicly available database. We found that among subjects with AD, individuals that reported hearing loss had smaller brainstem and cerebellar volumes in both hemispheres than individuals without hearing loss. In addition, we found that these brain volumes diminish in size more rapidly among normal subjects with reported hearing loss and that there was a significant interaction between cognitive diagnosis and the relationship between reported hearing loss and these brain volumes. These data suggest that hearing loss is linked to brainstem and cerebellar pathology, but only in the context of the pathological state of AD. We hypothesize that the presence of AD-related pathology in both the brainstem and cerebellum creates vulnerabilities in these brain regions to auditory deafferentation-related atrophy. These data have implications for our understanding of the potential neural substrates for interactions between hearing loss and AD.

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