Alzheimer Disease: Chan D

Good CD, Scahill RI, Fox NC, Ashburner J, Friston KJ, Chan D, Crum WR, Rossor MN, Frackowiak RS. · Wellcome Department of Cognitive Neurology, Institute of Neurology, University College London, 12 Queen Square, London WC1N 3BG, United Kingdom. · Neuroimage. · Pubmed #12482066 No free full text.

Abstract: We compared voxel-based morphometry (VBM) with independent accurate region-of-interest (ROI) measurements of temporal lobe structures in order to validate the usefulness of this fully automated and unbiased technique in Alzheimer's disease (AD) and semantic dementia (SD). In AD, ROI analyses appear more sensitive to volume loss in the amygdalae, whereas VBM analyses appear more sensitive to right middle temporal gyrus and regional hippocampal volume loss. In SD, ROI analyses appear more sensitive to left middle and inferior temporal gyrus volume loss, whereas VBM appears more sensitive to regional hippocampal volume loss. In addition the significance of volume reductions was generally less in VBM owing to more stringent corrections for multiple comparisons. In conclusion, the automated technique detects a general trend of atrophy similar to that of expertly labeled ROI measurements in AD and SD, although there are discrepancies in the ranking of severity and in the significance of volume reductions that are more marked in AD.

Chan D, Walters RJ, Sampson EL, Schott JM, Smith SJ, Rossor MN. · Dementia Research Group, National Hospital for Neurology, London, UK. · Neurology. · Pubmed #15136699 No free full text.

Abstract: The EEG appearances in patients with frontotemporal lobar degeneration (FTLD) were compared with those in patients with Alzheimer disease (AD). EEG abnormalities were found in 61% of FTLD patients, with the degree of EEG abnormality increasing with dementia severity. There was no significant difference in the severity of EEG abnormality between the FTLD and AD patient groups. These data suggest a need for reappraisal of the role of the EEG in the diagnostic differentiation of FTLD from AD.

Chan D, Janssen JC, Whitwell JL, Watt HC, Jenkins R, Frost C, Rossor MN, Fox NC. · Dementia Research Group, Department of Clinical Neurology, Institute of Neurology, University College London, London, UK. · Lancet. · Pubmed #14550701 No free full text.

Abstract: The extent to which cerebral atrophy in Alzheimer's disease changes with time is unknown. We used multiple MRI scans to measure progression of cerebral atrophy in 12 patients with Alzheimer's disease who were followed up from a presymptomatic stage through to moderately severe dementia. Analysis with hierarchical regression models with quadratic terms in time provided evidence of increasing yearly percentage losses in brain volume. At the time when patients were judged to have mild dementia (mini-mental state examination score MMSE=23), mean yearly loss of brain volume was 2.8% (95% CI 2.3-3.3), which rose by 0.32% per year (0.15-0.50). Our findings reinforce the need for early diagnosis and therapeutic intervention in Alzheimer's disease.

Schott JM, Fox NC, Frost C, Scahill RI, Janssen JC, Chan D, Jenkins R, Rossor MN. · Dementia Research Group, Institute of Neurology, University College London, Queen Square, United Kingdom. · Ann Neurol. · Pubmed #12557284 No free full text.

Abstract: Regional and global cerebral atrophy are inevitable features of Alzheimer's disease (AD). We assessed volumes and atrophy rates of brain structures in patients with familial AD during the period that they developed symptoms. Five patients with presymptomatic AD and 20 controls had two or more annual volumetric MRI brain scans. Volumes of brain, ventricles, temporal lobes, hippocampi, and entorhinal cortices (ECs) were measured. Rates of volume change were calculated from serial scans. There were no significant differences in baseline measures of whole brain, temporal lobe, or ventricular volume between patients and controls; averaged volumes of medial temporal lobe structures (both hippocampi and ECs) were 16.6% (95% confidence interval [CI], 3.3-28.0%) lower in patients. Atrophy rates for brain, temporal lobe, hippocampus, and EC were significantly increased in patients compared with controls (p < 0.05). Averaged atrophy rates from both hippocampi and ECs were 5.1% (95% CI, 3.0-7.1%) greater in patients than controls. Linear extrapolation backward suggested medial temporal lobe atrophy commenced 3.5 years (95% CI, 0.7-7.5 years) before onset, when all patients were asymptomatic. We conclude that increased medial temporal lobe atrophy rates are an early and distinguishing feature of AD and that pathological atrophy probably is occurring several years before the onset of symptoms.

Høgh P, Smith SJ, Scahill RI, Chan D, Harvey RJ, Fox NC, Rossor MN. · Dementia Research Group, Department of Clinical Neurology, Institute of Neurology, Queen Square, London, UK. · Neurology. · Pubmed #11805262 No free full text.

Abstract: Three patients with progressive memory impairment initially attributed to AD underwent serial neuropsychometry, MRI, and EEG. Registered serial MRI volumetric analysis showed no loss of whole or regional brain volume. EEG revealed temporal lobe spike activity and antiepileptic treatment was optimized. Memory functions improved with antiepileptic medication in all three patients. The demonstration of temporal lobe spike activity in patients with progressive memory impairment is an indication for a trial of antiepileptic medication.

Chan D, Fox NC, Jenkins R, Scahill RI, Crum WR, Rossor MN. · Dementia Research Group, Department of Clinical Neurology, Institute of Neurology, London, UK. · Neurology. · Pubmed #11723259 No free full text.

Abstract: OBJECTIVE: Serial registered MRI provides a reproducible technique for detecting progressive cerebral atrophy in vivo and was used to determine if there were differences between the rates of cerebral atrophy in AD and frontotemporal dementia (FTD). METHODS: Eighty-four patients with dementia (54 AD and 30 FTD) and 27 age-matched control subjects each had at least two volumetric MR scans. Serial scans were positionally matched (registered), and brain volume loss was determined by calculation of the brain boundary shift integral. RESULTS: There was a difference between the rates of whole-brain atrophy in patients (mean annual volume loss 2.7% of total brain volume) and in control subjects (mean annual volume loss 0.5%). AD and FTD were associated with different rates of atrophy (mean annual losses 2.4 and 3.2%). The range of atrophy rates in the FTD group (0.3 to 8.0%) greatly exceeded that in the AD group (0.5 to 4.7%). Frontal-variant FTD was associated with a wider range of atrophy rates than temporal-variant FTD. Analysis of regional brain atrophy rates revealed that there was widespread symmetrically distributed cerebral volume loss in AD, whereas in frontal FTD there was greater atrophy anteriorly and in temporal FTD the atrophy rate was greatest in the left anterior cerebral cortex. CONCLUSIONS: Both AD and FTD patients had increased rates of brain atrophy. Whereas the patients with AD were associated with a relatively restricted spread of atrophy rates, the greater spread of rates observed in the patients with FTD may reflect the heterogeneity of disease in FTD, with differences observed between frontal and temporal FTD. Increased rates of whole-brain atrophy did not discriminate AD from FTD, but analysis of regional atrophy rates revealed marked differences between patient groups.

Chan D, Crutch SJ, Warrington EK. · Dementia Research Group, Department of Clinical Neurology, Institute of Neurology, Queen Square, London WC1N 3BG, UK. · J Neurol Neurosurg Psychiatry. · Pubmed #11561036 links to  free full text

Abstract: A 64 year old woman with posterior cortical atrophy secondary to probable Alzheimer's disease is described. Her presenting symptom was of seeing objects as abnormally coloured after prior exposure to a coloured stimulus. Formal testing disclosed that the patient experienced colour after-images of abnormal latency, duration, and amplitude.The demonstration of prolonged colour after-images in a patient with a cortical disease process provides strong evidence that the generation of colour after-images is mediated at least in part by the visual cortex. A mechanism for the generation of colour after-images is proposed in which abnormal prolongation of the images results from excessive rebound inhibition of previously excited wavelength selective neurons in V1. This may occur as a consequence of the relative sparing of inhibitory interneurons in V1 in the context of the degeneration of excitatory neurons that occurs in Alzheimer's disease.

Chan D, Fox NC, Scahill RI, Crum WR, Whitwell JL, Leschziner G, Rossor AM, Stevens JM, Cipolotti L, Rossor MN. · Department of Clinical Neurology, Institute of Neurology, The National Hospital for Neurology and Neurosurgery, London, UK. · Ann Neurol. · Pubmed #11310620 No free full text.

Abstract: Volumetric magnetic resonance imaging analyses of 30 subjects were undertaken to quantify the global and temporal lobe atrophy in semantic dementia and Alzheimer's disease. Three groups of 10 subjects were studied: semantic dementia patients, Alzheimer's disease patients, and control subjects. The temporal lobe structures measured were the amygdala, hippocampus, entorhinal cortex, parahippocampal gyrus, fusiform gyrus, and superior, middle, and inferior temporal gyri. Semantic dementia and Alzheimer's disease groups did not differ significantly on global atrophy measures. In semantic dementia, there was asymmetrical temporal lobe atrophy, with greater left-sided damage. There was an anteroposterior gradient in the distribution of temporal lobe atrophy, with more marked atrophy anteriorly. All left anterior temporal lobe structures were affected in semantic dementia, with the entorhinal cortex, amygdala, middle and inferior temporal gyri, and fusiform gyrus the most severely damaged. Asymmetrical, predominantly anterior hippocampal atrophy was also present. In Alzheimer's disease, there was symmetrical atrophy of the entorhinal cortex, hippocampus, and amygdala, with no evidence of an anteroposterior gradient in the distribution of temporal lobe or hippocampal atrophy. These data demonstrate that there is a marked difference in the distribution of temporal lobe atrophy in semantic dementia and Alzheimer's disease. In addition, the pattern of atrophy in semantic dementia suggests that semantic memory is subserved by anterior temporal lobe structures, within which the middle and inferior temporal gyri may play a key role.

Chan D, Fox N, Rossor M. · No affiliation provided · Neurology. · Pubmed #11889267 No free full text.

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