Alzheimer Disease: Høgh P

Høgh P, Teller AS, Hasselbalch S, Waldemar G. · Memory Disorders Research Group, Department of Neurology, Copenhagen University Hospital, Rigshospitalet, Neuroscience Centre, Copenhagen, Denmark. · Dement Geriatr Cogn Disord. · Pubmed #17952007 No free full text.

Abstract: BACKGROUND: The aim of this study was to assess the accuracy of visual image rating as compared to parametric analysis of regional cerebral blood flow (rCBF) measured with SPECT in patients referred to a memory clinic for diagnostic evaluation of cognitive symptoms. METHODS: SPECT with (99m)Tc-HMPAO was used to determine rCBF in 47 patients and 26 healthy control subjects. The 47 patients (30 F/17 M) had a mean age of 74.6 years (range = 62-88) and mild or questionable dementia with an MMSE score of 24.8 (range = 20-30). Two experienced image readers blinded to the classifications and identity of subjects performed visual rating in consensus and the global and regional CBF patterns were evaluated and graded according to severity of hypoperfusion. Correlation coefficients were calculated using results from the parametric analyses as gold standard. RESULTS: The sensitivity and specificity of global visual rating (normal vs. abnormal SPECT) was 92 and 86%, respectively, yielding an overall accuracy of 89% for visual rating compared to parametric analysis. The correlation between visual rating and parametric analysis was highly significant (p < 0.001). CONCLUSION: Visual rating is a valid method for analyzing SPECT images in patients with mild or questionable dementia.

Bech-Azeddine R, Høgh P, Juhler M, Gjerris F, Waldemar G. · The University Clinic of Neurosurgery, Rigshospitalet, Copenhagen, Denmark. · J Neurol Neurosurg Psychiatry. · Pubmed #17012342 No free full text.

Abstract: OBJECTIVES: To elucidate the importance of clinically diagnosed cerebral comorbidity in idiopathic normal-pressure hydrocephalus (INPH) and its effect on improvement after shunt surgery as well as concordance with parenchymal pathological changes described in frontal cerebral biopsy specimens. METHODS: In 28 consecutive patients diagnosed with INPH and shunted according to clinical, radiological and cerebrospinal fluid dynamic criteria, concomitant disorders were carefully registered, with special emphasis on cerebrovascular disease (CVD) and possible Alzheimer's disease. During shunt surgery, a frontal cerebral biopsy specimen was obtained and subsequently analysed for pathological changes. RESULTS: One or several concurrent disorders were present in 89% of the patients, most often CVD (n = 17) and possible Alzheimer's disease (n = 12), of which eight patients presented both, diagnosed according to the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association. The shunt success rate was 33%. A clear tendency towards increasing prevalence of CVD or Alzheimer's disease was found in the subgroups with no improvement or clinical deterioration compared with the patients improving after shunt surgery. The presence of CVD tended towards an unfavourable shunt outcome. The pathological parenchymal changes reflected the clinical diagnoses of comorbidity, and were described in about half of the biopsy specimens, with Alzheimer's disease (n = 7) and vascular changes (n = 7) being the most common findings. However, no significant correlation was found with the clinical diagnoses of Alzheimer's disease and CVD. The presence of cerebral comorbidity, whether diagnosed clinically or by brain biopsy, did not preclude clinical improvement after shunt operation. CONCLUSIONS: A high prevalence of CVD and Alzheimer's disease was found in patients shunted for INPH, which was reflected, although less commonly, by similar neuropathological biopsy findings. No significant correlation was found between the presence of comorbidity and shunt outcome. The findings support the perception of INPH as a multiaetiological clinical entity, possibly overlapping pathophysiologically with CVD and Alzheimer's disease.

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.

Høgh P, Knudsen GM, Kjaer KH, Jørgensen OS, Paulson OB, Waldemar G. · Memory Disorders Research Unit, The Neuroscience Center, Copenhagen University Hospital, Rigshospitalet, Denmark. · J Geriatr Psychiatry Neurol. · Pubmed #11281316 No free full text.

Abstract: The aim of this study was to examine the impact of the apolipoprotein E (APOE) epsilon4 allele on semiquantitative regional cerebral blood flow (rCBF) in Alzheimer's disease. Single photon emission computed tomography technetium (SPECT) with (99m)Tc d,l-hexamethyl propylenamine oxine was used to determine rCBF in 41 consecutive patients (18 males/23 females) with probable Alzheimer's disease according to the National Institute of Neurological and Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association criteria (mean age 71.0 years; range 54-85). The mean Mini-Mental State Examination (MMSE) score was 20.4 (range 10-30). After normalization of CBF to mean blood flow in the cerebellum, values for rCBF in several cortical regions of interest, side-to-side asymmetry indices, and anterior-posterior ratios were calculated. Determination of the APOE genotype from blood samples was performed using restriction enzyme polymerase chain reaction technique. Multivariate regression analyses and the Wilcoxon rank-sum test for unpaired data (Mann-Whitney) were used for statistical analysis. The patients comprised 27APOE epsilon4-positive and 14APOE epsilon4-negative individuals. Five patients were APOE epsilon4 homozygotes. APOE epsilon4-positive patients had significantly reduced rCBF in the right frontal and left occipital lobes. On nonparametric analysis, the most prominent differences between epsilon4-negative and epsilon4-positive patients were demonstrated in subregions representing the frontal association cortex (Mann-Whitney, P < .01). Age-stratified analysis suggested that these findings could be demonstrated predominantly in the elderly patients. The results of this study suggest that the APOE genotype in itself may have an impact on the pattern of rCBF deficits in Alzheimer's disease. The more pronounced reduction of rCBF in frontal association cortex observed in elderly APOE epsilon4-positive patients might predict clinical progression.