Ren-Shyan Liu

Effects of estrogen on cognition, mood, and cerebral blood flow in AD A controlled study

Objective: To examine the effects of estrogen therapy on cognition, mood, and cerebral blood flow in patients with AD. Background: Some studies have suggested estrogen may be effective in the treatment of AD. However, most of these studies were not controlled adequately. Methods: Fifty female AD patients were recruited in a randomized, double-blind, placebo-controlled 12-week trial. Each member of the estrogen-treated group received conjugated estrogen (Premarin) 1.25 mg/day. The primary outcome measures were the Cognitive Ability Screening Instrument (CASI), Clinical Dementia Rating (CDR), and Clinician Interview-Based Impression of Change (CIBIC-plus). The secondary outcome measures were Behavioral Pathology in Alzheimer’s Disease (BEHAVE-AD), Hamilton Anxiety Rating Scale (HARS), Hamilton Depression Rating Scale (HDRS), and 99mTc hexamethylpropylene amine oxime SPECT of the brain. Results: No meaningful differences were found between the outcome measures (CASI, CDR, CIBIC-plus, BEHAVE-AD, HARS, HDRS, and cerebral blood flow) taken from the estrogen-treated group and those from the control group. Conclusion: A 1.25-mg/day dose of Premarin administered for 12 consecutive weeks does not produce a meaningful effect on cognitive performance, dementia severity, behavior, mood, and cerebral perfusion in female AD patients. Because estrogen therapy has been suspected of yielding adverse effects, and its therapeutic effectiveness is in doubt, additional evaluation of its role in AD treatment ought to be conducted.

Posterior ischemia during an attack of transient global amnesia.

Background The popular concept that cerebral ischemia causes transient global amnesia has been difficult to prove by cerebral blood flow studies during attacks because the transient global amnesia attacks are so short. Case Description We performed single-photon emission computed tomography (SPECT) of the brain and neuropsychological assessment in a 37-year-old woman during a 10-hour attack and twice thereafter. A neuropsychological evaluation 3 hours after the onset of transient global amnesia revealed severe impairment of recent memory and verbal fluency, both of which returned to normal 2 and 28 days later, respectively. A 99mTc-labeled hexamethylpropyleneamine oxime SPECT of the brain performed 6 hours after the onset showed multiple perfusion defects in both occipital lobes, the medial left temporal lobe, and the left thalamus. A second brain SPECT performed 3 days later showed perfusion defects in only the occipital regions. A third brain SPECT performed 28 days later was normal. The patients brain computed tomographic scan, electroencephalogram, duplex ultrasound of the carotid artery, and echocardiogram were normal Conclusions The perfusion defects revealed by the brain SPECT during the transient global amnesia attack indicated ischemia in the territory of the posterior cerebral arteries, which partially resolved in 3 days and completely resolved by 28 days.

Cognitive Reserve: A SPECT Study of 132 Alzheimer’s Disease Patients with an Education Range of 0–19 Years

This study examines the associations between education, cerebral perfusion, and cognitive test performance among 132 patients with Alzheimer’s disease. The participants had had between 0 and 19 years of formal schooling, and had either mild or moderate dementia according to the Clinical Dementia Rating Scale. Cerebral perfusion was evaluated by the 99mTc-hexamethylpropylene amine oxime single photon emission computed tomography. The Mini-Mental State Examination and the Cognitive Abilities Screening Instrument were used to assess cognitive performance. For patients at each clinical dementia severity level, statistical parametric mapping was used to examine voxel by voxel the association between education and cerebral perfusion, and Pearson’s correlation coefficients were calculated between education and cognitive test scores. Years of formal schooling had negative associations with cerebral perfusion and positive associations with cognitive test scores. The brain regions showing a significant education effect on perfusion involved bilateral posterior association areas in mild dementia, and bilateral parieto-temporo-frontal areas in moderate dementia. The present findings indicate that the cognitive reserve effect starts at the low end of the education range. They also suggest that the main effect of more education is a more facile use of alternative brain circuits instead of locally increased synaptic connections.

Selective Hypoperfusion of Anterior Cingulate Gyrus in Depressed AD Patients: A Brain SPECT Finding by Statistical Parametric Mapping

This study tests the hypothesis that depression in patients with Alzheimer’s disease (AD) is due to a specific pathogenesis rather than a reactive phenomenon. Forty-three AD patients received a psychiatrist’s interview, neuropsychological assessments, and a 99mTc-hexamethyl propyleneamine oxime single photon emission computed tomography (HMPAO-SPECT). Analysis by statistical parametric mapping (SPM) showed that the depressed group had selective hypoperfusion in the bilateral anterior and posterior cingulate gyri and precuneus. Using the Hamilton Depression Rating Scale as a parameter, an inverse correlation was found between cerebral perfusion and the severity of depression. The right anterior cingulate gyrus demonstrated a most significant reduction in perfusion. These locations are akin to the imaging findings in patients with primary depression, indicating a specific pathogenesis for depression in AD.

Cognition and 99Tcm-HMPAO SPECT in Parkinson's disease

99Tcm-hexamethylpropyleneamine oxime (HMPAO) single photon emission computed tomography (SPECT) of brain was performed in 43 unselected patients with Parkinsons disease to evaluate whether low cerebral perfusion on SPECT correlated with cognitive impairment in the patients. All patients received neurological, Mini-Mental State Examination and a neuropsychological assessment. Eighteen (41.9%) of the 43 patients were demented. Thirty patients (69.8%) had abnormal SPECT: 17 had perfusion defects in cortical regions, eight in basal ganglia and five in both regions. Of the 22 patients with abnormal cortical perfusion, 15 (68.2%) were demented; only three (14.3%) of the 21 patients without cortical defect were demented (P < 0.01). Twelve of the 15 demented patients had low perfusion in the parietal region alone or in parietal and occipital regions. The cortical perfusion defects, present in 22 (51.2%) Parkinsons patients, are highly correlated with cognitive impairment. The pattern of SPECT abnormality in most demented patients with Parkinsons disease is similar to that seen in Alzheimers disease, suggesting that the underlying pathophysiology for dementia in patients with Parkinsons disease may be similar to that in Alzheimers disease.

Statistical Parametric Mapping of Brain SPECT Perfusion Abnormalities in Patients with Alzheimer’s Disease

Brain perfusion in 20 patients with mild Alzheimer’s disease (AD), 20 patients with moderate AD and 20 control subjects (matched for age, gender and education) were assessed by single photon emission computed tomography (SPECT) using technetium-99m hexamethylpropylene amine oxime (99mTc-HMPAO). SPECT images were transformed to a standard size and shape for group comparisons by the voxel-based t test of the statistical parametric mapping techniques. Cerebral hypoperfusion in the left lower parietal area was found in mild AD patients. In moderate AD patients, significant cerebral hypoperfusion was located in bilateral posterior parietotemporal cortices, contiguous anterior occipital lobes, posterior cingulate gyri and, to a lesser extent, in frontal areas.

Technetium-99m hexamethylpropylene amine oxime single photon emission tomography of the brain in early Parkinson's disease: correlation with dementia and lateralization

Regional cerebral blood flow was assessed in 19 patients with early idiopathic Parkinsons disease (PD) and 12 control subjects of similar age by single-photon emission tomography using technetium-99m hexamethylpropylene amine oxime (HMPAO). Of the patients with PD, seven were mildly demented and 15 presented with hemiparkinsonism. Mean HMPAO cortical or basal ganglia/cerebellum activity ratios were calculated. Mean cortical and regional uptake ratios in non-demented PD patients were not significantly different from values in the controls. In contrast, besides generalized cortical hypoperfusion, demented PD patients had significantly lower HMPAO uptake in the frontal and basal ganglia regions than non-demented patients. These observations support the hypothesis of impaired neuronal activity in both cortical and subcortical regions of the brain in demented PD patients. In hemiparkinsonian patients, the only asymmetrical finding was a relative hypoperfusion in the contralateral parietal region. This may be due to deafferentation of the thalamoparietal pathways. The lack of asymmetrical uptake in basal ganglia in our PD patients may be explained by their staging at the time of the investigation (stage I and II, Hoehn and Yahr scale).

Efficacy of quantitative cholescintigraphy in the diagnosis of sphincter of Oddi dysfunction

: The diagnostic efficacy of time-activity curves (TAC) and common bile duct dynamics (CBDD) derived from quantitative cholescintigraphy (QC) was assessed in patients with suspected sphincter of Oddi dysfunction (SOD). Quantitative cholescintigraphy was performed on 34 cholecystectomized individuals with suspected SOD and 26 asymptomatic controls. Each patient with suspected SOD underwent endoscopic retrograde cholangiography and sphincter of Oddi manometry (SOM). After exclusion of eight patients because of failure of manometry, the final diagnoses of the remaining 26 patients were taken as the gold standard by which to determine the detectability of TAC and CBDD. The sensitivity of TAC reached 68.8%. Common bile duct dynamics showed equal sensitivity but was more specific than TAC. The sensitivity improved to 87.5% when TAC and CBDD were combined. We conclude that non-invasive QC provides good sensitivity and specificity in evaluating cholecystectomized patients with suspected SOD.The diagnostic efficacy of time-activity curves (TAC) and common bile duct dynamics (CBDD) derived from quantitative cholescintigraphy (QC) was assessed in patients with suspected sphincter of Oddi dysfunction (SOD). Quantitative cholescintigraphy was performed on 34 cholecystectomized individuals with suspected SOD and 26 asymptomatic controls. Each patient with suspected SOD underwent endoscopie retrograde cholangiography and sphincter of Oddi manometry (SOM). After exclusion of eight patients because of failure of manometry, the final diagnoses of the remaining 26 patients were taken as the gold standard by which to determine the detectability of TAC and CBDD. The sensitivity of TAC reached 68.8%. Common bile duct dynamics showed equal sensitivity but was more specific than TAC. The sensitivity improved to 87.5% when TAC and CBDD were combined. We conclude that non-invasive QC provides good sensitivity and specificity in evaluating cholecystectomized patients with suspected SOD.

Single photon emission computed tomography using 99Tcm-HMPAO in Alzheimer's disease.

Brain single photon emission computed tomography (SPET) using 99mTcm-hexamethylpropyleneamine oxime (HMPAO) was performed in 37 patients satisfying the standard clinical criteria of Alzheimers disease (AD), correlating results with patients age of onset, duration of illness, severity of dementia, neuropsychological impairment, computed tomography (CT) and EEG findings. All patients had abnormal SPET: 23 were bilaterally symmetric, 10 were bilaterally asymmetric and four showed unilateral low regional cerebral perfusion. Low perfusion in bilateral parietal regions was the most consistent finding and was present alone or with other abnormal regions in 31 patients (84%). The only significant clinical correlation was found between asymmetric SPET changes and onset of disease before the age of 65 years. Fifty per cent of patients with presenile onset, but only 19% with senile onset had asymmetric low regional cerebral perfusion. Fifteen of the 36 patients had normal brain CT scans, and 9 of 31 patients receiving EEG examination had normal results. Although clinical evaluation is the most valuable diagnostic tool, brain SPET is a sensitive test for physiological investigation in AD.

Cerebral involvement in spinal and bulbar muscular atrophy (Kennedy's disease): A pilot study of PET

OBJECTIVEnTo investigate possible cerebral involvement in patients with spinal and bulbar muscular atrophy (SBMA) by (18)F-fluorodeoxyglucose-positron emission tomography (FDG-PET).nnnDESIGNnTen patients with molecularly-confirmed SBMA and 5 age- and gender-matched healthy controls were recruited for brain FDG-PET studies. The data were analyzed and compared using the statistical parametric mapping (SPM) method.nnnRESULTSnGlucose hypometabolism in frontal areas of the cerebrum was found in patients with SBMA. However, no significant correlation with clinical variables, such as CAG repeat length, age at onset, or serum testosterone levels, was noted.nnnCONCLUSIONSnThe perturbation of cerebral glucose metabolism in patients with SBMA argues against SBMA being a pure lower motor and sensory neuron syndrome. Mutations in the androgen receptor gene might have a more widespread effect in the cerebrum than previously recognized.