Hidekazu Kanetaka

Efficacy of PPAR-γ agonist pioglitazone in mild Alzheimer disease

To test the effects of the PPAR-γ agonist pioglitazone on cognition, regional cerebral blood flow (rCBF), and plasma levels of Aβ40 and Aβ42, we conducted a 6-month, randomized, open-controlled trial in patients with mild Alzheimer disease (AD) accompanied with type II diabetes mellitus. We randomly assigned 42 patients to either the group treated with 15-30 mg pioglitazone daily (n=21, pioglitazone group) or not (n=21, control group). The pioglitazone group improved cognition and rCBF in the parietal lobe, while the control group showed no such improvement. The plasma Aβ40/Aβ42 ratio increased in the control group, but showed no significant change in the pioglitazone group. Both groups showed good control of diabetes during the study. In addition, pioglitazone treatment resulted in a decrease in fasting plasma insulin levels, indicating enhanced insulin sensitivity. The results of this pilot study demonstrated that pioglitazone exhibited cognitive and functional improvements, and stabilization of the disease in diabetic patients with AD. Pioglitazone may offer a novel strategy for the treatment of AD.

Comparative value of brain perfusion SPECT and [123I]MIBG myocardial scintigraphy in distinguishing between dementia with Lewy bodies and Alzheimer’s disease

PurposeBoth decreased occipital perfusion on brain single-photon emission computed tomography (SPECT) and reduction in cardiac 123I-metaiodobenzylguanidine (MIBG) uptake are characteristic features of dementia with Lewy bodies (DLB), and potentially support the clinical diagnosis of DLB. The aim of this study was to compare the diagnostic value of these two methods for differentiation of DLB from Alzheimer’s disease (AD).MethodsThe study population comprised 19 patients with probable DLB and 39 patients with probable AD who underwent both SPECT with N-isopropyl-p-[123I]iodoamphetamine and MIBG myocardial scintigraphy. Objective and quantitative measurement of perfusion in the medial occipital lobe, including the cuneus and lingual gyrus, was performed by the use of three-dimensional stereotactic surface projections.ResultsMedial occipital perfusion was significantly decreased in the DLB group compared with the AD group. The mean heart/mediastinum ratios of MIBG uptake were significantly lower in the DLB group than in the AD group. Although SPECT failed to demonstrate significant hypoperfusion in the medial occipital lobe in five patients with DLB, marked reduction of MIBG uptake was found in all patients with DLB. Receiver operating characteristic analysis revealed that MIBG myocardial scintigraphy enabled more accurate discrimination between DLB and AD than was possible with perfusion SPECT.ConclusionMIBG myocardial scintigraphy may improve the sensitivity in the detection of DLB. In particular, this method may provide a powerful differential diagnostic tool when it is difficult to distinguish cases of DLB from AD using brain perfusion SPECT.

Effects of partial volume correction on discrimination between very early Alzheimer's dementia and controls using brain perfusion SPECT.

We assessed the accuracy of brain perfusion single-photon emission computed tomography (SPECT) in discriminating between patients with probable Alzheimer’s disease (AD) at the very early stage and age-matched controls before and after partial volume correction (PVC). Three-dimensional MRI was used for PVC. We randomly divided the subjects into two groups. The first group, comprising 30 patients and 30 healthy volunteers, was used to identify the brain area with the most significant decrease in regional cerebral blood flow (rCBF) in patients compared with normal controls based on the voxel-based analysis of a group comparison. The second group, comprising 31 patients and 31 healthy volunteers, was used to study the improvement in diagnostic accuracy provided by PVC. A Z score map for a SPECT image of a subject was obtained by comparison with mean and standard deviation SPECT images of the healthy volunteers for each voxel after anatomical standardization and voxel normalization to global mean or cerebellar values using the following equation: Z score = ([control mean]−[individual value] )/(control SD). Analysis of receiver operating characteristics curves for a Z score discriminating AD and controls in the posterior cingulate gyrus, where a significant decrease in rCBF was identified in the first group, showed that the PVC significantly enhanced the accuracy of the SPECT diagnosis of very early AD from 73.9% to 83.7% with global mean normalization. The PVC mildly enhanced the accuracy from 73.1% to 76.3% with cerebellar normalization. This result suggests that early diagnosis of AD requires PVC in a SPECT study.

Differentiation of Dementia with Lewy Bodies from Alzheimer’s Disease Using Brain SPECT

We compared regional cerebral blood flow (CBF) patterns in patients with dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD) using single photon emission computed tomography (SPECT) and investigated the diagnostic utility of SPECT study in differentiating between DLB and AD. SPECT data on 20 patients with DLB and 75 patients with AD were analyzed using three-dimensional stereotactic surface projections. Regional CBF reduction was determined by quantitative analysis using stereotactic extraction estimation method. The DLB group showed a significant CBF reduction in the temporoparietal, frontal lobe and posterior cingulate, similar to the CBF pattern in the AD group, but regional CBF in the medial and lateral occipital lobes decreased significantly in patients with DLB compared with patients with AD. Receiver operating characteristic analysis revealed that regional CBF measurement of the medial occipital lobe, including the cuneus and lingual gyrus, yielded a sensitivity of 85% and a specificity of 85% in discriminating DLB from AD. Objective and quantitative CBF measurement in the medial occipital lobe may be useful in the clinical differentiation of DLB and AD.

The progression of cognitive deterioration and regional cerebral blood flow patterns in Alzheimer's disease: A longitudinal SPECT study

BACKGROUND AND PURPOSE The progression of cognitive deterioration in patients with Alzheimers disease (AD) is considerably variable. The ability to predict the progression rate is important for clinicians to treat and manage patients with AD. We examined the possible relationship between the rate of cognitive deterioration and regional cerebral blood flow (rCBF) patterns in patients with AD. METHODS We followed 48 patients with AD for an average of 37 months. They were subsequently divided into the rapidly progressing group (n=24) and slowly progressing group (n=24) based on an annual Mini-Mental State Examination (MMSE) score change. Initial and follow-up rCBF were assessed using single photon emission CT (SPECT) and the SPECT data were analyzed by 3D-stereotactic surface projections. RESULTS At initial evaluation, the rapidly progressing group had greater rCBF deficits mainly in the parietotemporal and frontal regions, and left posterior cingulate than did the slowly progressing group. When compared with initial SPECT, follow-up SPECT showed a significant rCBF reduction in widespread regions, including parietotemporal and frontal lobes, of the rapidly progressing group, while showed in the scattered and small regions of hemispheres of the slowly progressing group. CONCLUSION Our longitudinal SPECT study suggests a significant association between rCBF deficits in the parietotemporal, posterior cingulate, and frontal regions and subsequent rapid cognitive and rCBF deterioration.

Differences in clinical course between dementia with Lewy bodies and Alzheimer’s disease

Background and purpose:  To investigate whether there may be differences in the clinical course and changes in cognitive progression between dementia with Lewy bodies (DLB) and Alzheimer’s disease (AD).

Brain SPET abnormalities in Alzheimer's disease before and after atrophy correction.

Abstract. The aim of this study was to determine which brain structures show the greatest influence of partial volume effects (PVE) in single-photon emission tomography (SPET) studies on Alzheimers disease (AD). Brain perfusion SPET was performed in 30 patients with probable AD and 62 age-matched healthy volunteers. SPET images were corrected for PVE using grey matter volume segmented from magnetic resonance images. The most prominent changes after PVE correction were observed in the medial temporal structures. The PVE correction revealed a selective decrease in regional cerebral blood flow (rCBF) in the parahippocampal gyrus of AD without rCBF decreases in the hippocampus, which had been observed before correction. This correction seems to be essential in order to achieve accurate measurements of rCBF in SPET, which has limited spatial resolution.

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).

Regional cerebral blood flow changes in patients with idiopathic REM sleep behavior disorder.

Background:  Recent studies have shown an association between rapid eye movement sleep behavior disorder (RBD) and neurodegenerative disorders, especially alpha‐synucleinopathies.

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.