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Home , Precuneus, Uncus

Division of Clinical Neuroscience

NEUROIMAGING FINDINGS IN ALZHEIMER’S DISEASE: COORDINATE BASED RANDOM EFFECTS SIZE META-ANALYSES OF WHOLE BRAIN VOXEL-BASED MORPHOMETRY STUDIES RIGHT (3 -54 30)

Dr Christopher Tench, Research Fellow, Division of Clinical Neurosciences, University of Nottingham

Dr Ketan Jethwa, NIHR Academic Clinical Fellow, Department of Radiological Sciences, University of Nottingham ([email protected])

Introduction

Alzheimer’s disease (AD) is a neuropsychiatric disorder characterised by cognitive The precuneus is a structure in the which plays a central impairment and functional decline. Voxel-based morphometry studies have role in integrating multimodal sensory information, retrieval and identified a number of areas of loss in the temporal, parietal and self-processing function. The degree of glucose hypometabolism in the precuneus frontal lobes. Coordinate based random effects size meta-analyses were is associated with the degree of autobiographical memory impairment in AD. performed to identify patterns of cortical loss most characteristic of AD. RIGHT (26 -6 -36) Methods

A MEDLINE/PubMed and Google Scholar electronic search, handsearching of selected journals and personal communication with other researchers in the field were undertaken to gather whole brain VBM analyses assessing grey matter loss in studies comparing AD patients with controls. Only studies reporting coordinates in Montreal Neurological Institute (MNI) or Talaraich (Tal) space were included. Region of interest studies were excluded.

Demographic and clinical data were extracted. Coordinates and effect sizes (t or Z statistics) were extracted. Coordinate based random effects (CBRES) meta- analysis statistically identifies where reported coordinates from published studies The uncus forms the anterior extremity of the parahippocampal . The uncus are in better agreement (in both spatial location and effect size concordance) than is affected early in the course of AD. Tau tangle pathology ascends as AD expected by chance. CBRES avoids type 1 error. progresses, beginning in the base of the and then extending to Results limbic structures (including the ) and the wider neocortex.

The final selection list consisted of 36 publications comprising 2133 subjects (986 NUMBERS OF STUDIES CONTRIBUTING TO CLUSTERS AD patients). The mean age of patients was 71 years and the mean Mini Mental State Examination (MMSE) score of patients was 20. LEFT 25 RIGHT PARAHIPPOCAMPAL GYRUS 22 CBRES meta-analysis identified the following clusters of grey matter loss in AD LEFT HIPPOCAMPUS 13 (MNI coordinates). All clusters were statistically significant (p<0.05). RIGHT HIPPOCAMPUS 13 RIGHT INSULAR CORTEX 10 LEFT PARAHIPPOCAMPAL GYRUS (-24 -11 -14) RIGHT 6 RIGHT PARAHIPPOCAMPAL GYRUS (22 -4 -16) RIGHT PRECUNEUS 6 RIGHT UNCUS 6 LEFT 5

Limitations Small sample sizes and heterogenous handling of data within studies limits the findings of this analysis. This review has not addressed whether these changes are specific to AD and has not considered the effects of psychotropic medications.

Discussion Neurodegeneration isolates the hippocampus proper by preferentially affecting the This CBRES meta-analysis has identified statistically significant clusters of grey parahippocampal gyri in AD. Bilateral parahippocampal gyral atrophy is an matter loss characteristic of Alzheimer’s disease and these account for the core established finding in AD and correlates with declarative memory deficits and cognitive symptoms observed clinically. delayed .

Methods paper http://biorxiv.org/content/early/2016/11/25/089565 RIGHT (36 5 8) LEFT HIPPOCAMPUS (-25 -34 -2)

RIGHT MIDDLE TEMPORAL GYRUS (54 -28 -4) RIGHT HIPPOCAMPUS (31 -30 -5) https://www.nottingham.ac.uk/research/groups/clinicalneurology/neuroi.aspx

Atrophy of medial temporal structures, including the insular cortex, are characteristic of AD and are related to more severe cognitive deficits, neuropsychiatric symptoms, autonomic dysregulation and mortality. EP.1024