Kazumasa Kume

Effects of telmisartan on cognition and regional cerebral blood flow in hypertensive patients with Alzheimer's disease

Aim:  Recent studies have shown that some antihypertensive medications are associated with a significant reduction in the incidence of Alzheimers disease (AD). However, it remains uncertain whether antihypertensive drugs may have a preventive effect on cognitive decline in patients with AD. We investigated the effects of telmisartan, an angiotensin II type 1 receptor blocker with peroxisome proliferator‐activated receptor γ‐stimulating activity, on cognition and regional cerebral blood flow (rCBF) in elderly hypertensive patients with AD.

Effects of cilostazol on cognition and regional cerebral blood flow in patients with Alzheimer's disease and cerebrovascular disease: a pilot study.

Aim:  It remains unknown whether antiplatelet agents have a preventive effect on cognitive decline in patients with Alzheimers disease (AD). We investigated the effects of cilostazol, an antiplatelet agent and cyclic adenosine monophosphate phosphodiesterase 3 inhibitor, on cognition and regional cerebral blood flow (rCBF) in elderly patients with AD and cerebrovascular disease (CVD).

Japanese version of the Test Your Memory as a screening test in a Japanese memory clinic

A self-administered cognitive test (Test Your Memory, TYM) is designed as a screening test for the detection of Alzheimer disease (AD). We compared the diagnostic utility of the Japanese version of the TYM (TYM-J) in AD and mild cognitive impairment (MCI) with that of the Mini-Mental State Examination (MMSE) and Alzheimers Disease Assessment Scale-Cognitive Subscale Japanese version (ADAS-Jcog). We studied 79 patients with mild AD, 46 with MCI and 34 normal controls. The sensitivity and specificity of each test in the diagnosis of AD and MCI were compared. The average total TYM-J scores were 45.7 in controls, 41.7 in MCI, and 35.7 in AD. The TYM-J scores showed good correlations with other neuropsychological tests. The receiver operating characteristic analysis demonstrated that the TYM-J could better discriminate AD from controls and MCI from controls than the other tests. With each optimal cut-off score of the TYM-J, the sensitivity and specificity were 96% and 91% for diagnosing AD, and 76% and 74% for diagnosing MCI, respectively. The TYM-J is useful for the diagnosis of AD and MCI, and can be applied as a screening test in a Japanese memory clinic.

Telomere length shortening in patients with dementia with Lewy bodies

Background and purpose:  Shortened telomere length has been considered to be associated with various age‐related diseases, especially in dementia such as Alzheimer’s disease and vascular dementia. However, changes in telomere length in dementia with Lewy bodies (DLB) remain unclear. To elucidate these changes, we set out to determine telomere length in peripheral leukocytes as well as the level of urinary 8‐hydroxy‐deoxyguanosine (8‐OHdG) as a marker of oxidative stress in DLB.

Frontal Assessment Battery and brain perfusion images in amnestic mild cognitive impairment

Aim:  Some patients with mild cognitive impairment (MCI) may have impaired frontal lobe function. To assess the frontal lobe functions of subjects with MCI using the Frontal Assessment Battery (FAB) and to identify the brain regions responsible for FAB performance.

THE 1‐MINUTE MENTAL STATUS EXAMINATION IN THE MEMORY CLINIC

nonagenarian patients following hip fracture surgery. Gerontology 2003;49: 414–415. 8. Inouye SK, Peduzzi PN, Robison JT et al. Importance of functional measures in predicting mortality among older hospitalized patients. JAMA 1998;279:1187– 1193. 9. Somme D, Maillet JM, Gisselbrecht M et al. Critically ill old and the oldest-old patients in intensive care: Short and long-term outcomes. Intens Care Med 2003;29:2137–2143.

Regional differences in cortical benzodiazepine receptors of Alzheimer, vascular, and mixed dementia patients

OBJECTIVE We examined regional benzodiazepine receptors (rBZR) using single photon emission CT (SPECT) in patients with Alzheimer disease (AD), vascular dementia (VaD), and mixed AD/VaD dementia (MD) and compared the changes in the availability of rBZR with those of regional cerebral blood flow (rCBF). METHODS A total of 7 patients with AD, 6 with MD, and 9 with VaD underwent SPECT studies with N-isopropyl-p-[(123)I] iodoamphetamine and (123)I-iomazenil to measure rCBF and rBZR. The ratios of rCBF and rBZR uptake in brain subregions to the average global activity were compared among these diseases. In addition, we acquired z-score maps using 3-dimensional stereotactic surface projections of SPECT data. RESULTS Compared with AD, VaD and MD showed rCBF and rBZR reduction predominantly in the frontal lobe, but rBZR images revealed more extensive and severe defects than rCBF images. In contrast, AD showed rCBF and rBZR reduction predominantly in the parietotemporal lobe compared with VaD and MD, but rCBF images revealed more extensive defects than rBZR images. CONCLUSION rCBF imaging can detect parietotemporal abnormalities in AD, while rBZR imaging may enable the demonstration of underlying pathophysiological differences in the frontal lobe between VaD, MD and AD, reflecting neuronal integrity in the cerebral cortex.

Differentiation of dementia with Lewy bodies from Alzheimer disease using the frontal assessment battery test.

The profiles of cognitive impairment in dementia with Lewy bodies (DLB) are different from those in Alzheimer disease (AD). In addition to prominent visuospatial dysfunction and less memory impairment, deficits in attention and executive functions are characteristic features of DLB. The established neuropsychological tests of frontal lobe functions, such as the Winsconsin Card Sorting Test and Stroop Test, are relatively time-consuming, and are both difficult and distressing for elderly patients with dementia. The Frontal Assessment Battery (FAB) was recently developed as a short bedside cognitive and behavioral battery to assess frontal lobe functions (Dubois et al., 2000). The FAB is reported to be a valid and reliable screening test for evaluating executive dysfunction in AD, frontotemporal dementia (Lipton et al., 2005), and vascular dementia (Oguro et al., 2006). In the present study, we compared the FAB scores in patients with DLB and AD to determine whether the FAB test could differentiate DLB from AD. We recruited 28 patients with probable DLB and 69 patients with probable AD from outpatients attending the Memory Clinic of our department. We established a diagnosis in each case using the Consortium on DLB International Workshop (CDLB) clinical criteria (McKieth et al., 2005) and the National Institute of Neurological and Communicative Disorders and Stroke and Alzheimer’s Disease and Related Disorders Association (NINCDSADRDA) criteria. The normal control (NC) group consisted of 29 elderly subjects without any history or symptoms of neurologic or psychiatric diseases. We administered the Mini-Mental State Examination (MMSE), Wechsler Memory Scale—revised (WMS-R) logicalmemory-I and -II,Alzheimer’sDiseaseAssessment

DIFFERENCE IN OLFACTORY DYSFUNCTION WITH DEMENTIA WITH LEWY BODIES AND ALZHEIMER'S DISEASE

To the Editor: Olfactory deficits have been well documented in Alzheimer’s disease (AD) and Parkinson’s disease (PD). Olfactory impairment occurs in the early and even presymptomatic stages of diseases. The neuropathological basis of olfactory dysfunction is considered to be partly due to accumulations of tau pathology in AD and a-synuclein pathology in PD in the entorhinal cortex and olfactory bulb. Recent clinicopathological studies showed that anosmia occurs more frequently in people with dementia with Lewy bodies (DLB) than in patients with AD, indicating that anosmia is associated with Lewy bodies rather than AD pathology. Another study also found olfactory impairment to be more marked in patients with DLB than in those with AD. In the present study, smell identification performance in people with DLB was compared with that in people with AD to determine whether it could be a useful method for differentiation. Forty-eight people with probable AD and 38 with probable DLB were recruited from among outpatients attending the memory clinic of the Department of Geriatric Medicine, Tokyo Medical University (Tokyo, Japan). A diagnosis was established in each case using the criteria of the National Institute of Neurological and Communicative Disorders and StrokeFAlzheimer’s Disease and Related Disorders Association and the Consortium on DLB International Workshop clinical criteria. All patients had mild to moderate dementia and a Mini-Mental State Examination (MMSE) score of 18 or greater. The control group consisted of 31 older adults without any history or symptoms of neurological or psychiatric diseases. People with a history of sinus diseases or smoking within the past 5 years were excluded. The ethics committee of Tokyo Medical University approved this study. The Open Essence Smell Identification test, recently developed specifically for Japanese people and with confirmed utility in clinical olfactory dysfunction evaluation, was used. The test consists of 12 odorants, including Indian ink, wood, perfume, menthol, orange, curry, cooking gas, rose, hinoki (Japanese cypress wood), socks that smell of sweat, condensed milk, and roasted garlic. For each odorant, the subject is presented with a card showing four odor names and two alternative answers (unknown and not detected) and is asked to select one. The total number of correct answers for the 12 odorants presented is the smell identification score. Values are expressed as means standard deviations. Statistical analysis was performed using the Student t-test and chi-square test. MMSE scores and smell identification test results were analyzed using a nonparametric Kruskal-Wallis test and the Mann-Whitney U test (posthoc analysis). Po.05 was considered to represent a statistically significant difference. The sensitivity and specificity for differentiating DLB from AD were assessed using receiver operating characteristic (ROC) analysis. Table 1 shows demographic data and smell identification scores for the study groups. No significant differences in age, sex, or education were found between the three groups. MMSE scores were significantly lower in the AD and DLB groups than in the control group. Duration of symptoms and MMSE scores in the AD and DLB groups were comparable. Smell identification scores were significantly lower in the AD and DLB groups than in the control group and significantly lower in the DLB group than in the AD group. ROC analysis demonstrated that the smell identification score area under the ROC curve was 0.713 in the differentiation of DLB from AD. The smell identification test achieved the highest level of differentiation between DLB and AD, with a sensitivity of 47% and a specificity of 81% and an optimal cutoff score of 2. This study found that smell identification was more markedly impaired in the AD and DLB groups than in the control group. In addition, patients with DLB performed significantly worse than those with AD on the smell identification test, similar to previous studies. Moreextensive neuropathology in the central olfactory regions in DLB than in AD or nigrostriatal dopaminergic denervation in DLB may explain these results. The sensitivity for differentiating DLB from AD using the smell identification test was low, but the specificity was high. Therefore, this test may emerge as potential means of supporting the clinical diagnosis of DLB when core features, such as extrapy-

Rate of progression of Alzheimer's disease in younger versus older patients: A longitudinal single photon emission computed tomography study

Aim:  Although several researchers have examined the effect of age on disease progression in patients with Alzheimers disease (AD), the results are controversial. We investigated the effect of age on the rate of progression of cognitive impairment and on regional cerebral blood flow (rCBF) deficits using longitudinal single photon emission computed tomography (SPECT) studies.