Alzheimer Disease: Cutler D

Archer HA, McFarlane F, Frost C, Cutler D, Fox NC, Rossor MN. · Institute of Neurology, Dementia Research Centre, London School of Hygiene and Tropical Medicine, Keppel St, London, UK. · Alzheimer Dis Assoc Disord. · Pubmed #17545734 No free full text.

Abstract: BACKGROUND: Symptoms of memory loss are very common with estimated prevalence between 22% and 50% in those older than 65 years of age. Those with symptoms of memory loss and impaired performance on memory tests are at high risk of progression to Alzheimer disease. The relative importance of different aspects of the clinical history in predicting cognitive impairment is uncertain. METHODS: Fifty-six patients with symptoms of memory loss were recruited from the National Hospital for Neurology and Neurosurgery. A clinician recorded type and duration of memory symptoms as perceived by the patient and their informant, and use of memory aids. All patients subsequently underwent magnetic resonance imaging (MRI) and neuropsychologic testing. FINDINGS: (i) Informant, but not patient, ratings of memory were associated with performance on tests of memory function and with hippocampal size on MRI. (ii) Decreased use of memory aids and shorter duration of memory symptoms were more common in those with memory impairment. INTERPRETATION: In a clinical setting, information gathered from the history was associated with cognitive impairment on memory testing and brain appearances on MRI. The history from a close informant is particularly important being more strongly predictive of cognitive impairment (P=0.0002) than subjective symptoms, use of memory aids or duration of symptoms.

Edison P, Archer HA, Hinz R, Hammers A, Pavese N, Tai YF, Hotton G, Cutler D, Fox N, Kennedy A, Rossor M, Brooks DJ. · MRC Clinical Sciences Centre and Division of Neuroscience, Hammersmith Hospital, Imperial College London, London, UK. · Neurology. · Pubmed #17065593 No free full text.

Abstract: OBJECTIVE: To investigate the association between brain amyloid load in Alzheimer disease (AD) measured by [11C]PIB-PET, regional cerebral glucose metabolism (rCMRGlc) measured by [18F]FDG-PET, and cognition. METHODS: Nineteen subjects with AD and 14 controls had [11C]PIB-PET and underwent a battery of psychometric tests. Twelve of those subjects with AD and eight controls had [18F]FDG-PET. Parametric images of [11C]PIB binding and rCMRGlc were interrogated with a region-of-interest atlas and statistical parametric mapping. [11C]PIB binding and rCMRGlc were correlated with scores on psychometric tests. RESULTS: AD subjects showed twofold increases in mean [11C]PIB binding in cingulate, frontal, temporal, parietal, and occipital cortical areas. Higher cortical amyloid load correlated with lower scores on facial and word recognition tests. Two patients fulfilling the clinical criteria for AD had normal [11C]PIB at baseline. Over 20 months this remained normal in one but increased in the cingulate of the other. Mean levels of temporal and parietal rCMRGlc were reduced by 20% in AD and these correlated with mini mental scores, immediate recall, and recognition memory test for words. Higher [11C]PIB uptake correlated with lower rCMRGlc in temporal and parietal cortices. CONCLUSION: [11C]PIB-PET detected an increased amyloid plaque load in 89% of patients with clinically probable Alzheimer disease (AD). The high frontal amyloid load detected by [11C]PIB-PET in AD in the face of spared glucose metabolism is of interest and suggests that amyloid plaque formation may not be directly responsible for neuronal dysfunction in this disorder.

Archer HA, Macfarlane F, Price S, Moore EK, Pepple T, Cutler D, Frost C, Fox NC, Rossor MN. · Institute of Neurology, Dementia Research Centre, London, WC1N 3BG. · Int J Geriatr Psychiatry. · Pubmed #16977678 No free full text.

Abstract: BACKGROUND: Symptoms of memory loss are a common complaint within the general population and a frequent reason for seeking medical advice. However, the clinical relevance of these symptoms to future development of neurodegenerative disease is uncertain. The aim of this study is to characterise a cohort of individuals with symptoms of memory loss and varying memory impairment, who will be followed longitudinally with serial neuropsychology and neuroimaging to evaluate the clinical relevance of symptoms of memory loss. METHOD: Fifty-eight subjects with symptoms of memory loss were recruited from the National Hospital for Neurology and Neurosurgery. All subjects underwent clinical assessment, APOE4 genotyping, neuroimaging and neuropsychological tests. RESULTS: Those with mild cognitive impairment (MCI) had an increased prevalence of the APOE4 allele, impaired performance on tests of memory, measures of IQ and naming compared to controls. Baseline brain volumes were decreased and ventricular size increased. Those with symptoms of memory loss but no cognitive impairment (SNCI) performed significantly worse on tests of memory than the control group. CONCLUSIONS: The MCI represent a group with multiple risk factors for progression to AD. The SNCI group may represent a heterogeneous group with some individuals in the early stages of AD whilst others' memory complaints are more likely linked to anxiety or personality traits.