A Pilot Study on Cerebral Blood Flow and Mini-Mental State Examination to Predict Amyloid Deposition in Preclinical Alzheimer's Disease.

Background: Earlier differential diagnosis of dementia remains a major challenge. Although amyloid deposition by positron emission tomography is an emerging standard for the diagnosis of Alzheimer's disease, it is too expensive for routine use in clinical settings. We conducted a pilot study on the potential usefulness of single-photon emission computed tomography and the Mini-Mental State Examination to predict amyloid positron emission tomography positivity in preclinical Alzheimer's disease. Methods: Eighteen subjects, including 11 with mild cognitive impairment and 7 with subjective cognitive decline, underwent 18F-florbetapir positron emission tomography, 99mTc-ethylcysteinate dimer cerebral perfusion single-photon emission computed tomography, and the Mini-Mental State Examination. For the assessment of amyloid deposition, visual judgment as a qualitative method and a semiautomatic software analysis as a quantitative method were used. Results: Six subjects were judged as amyloid positive, including 4 mild cognitive impairment and 2 subjective cognitive decline subjects. Compared to the amyloid positron emission tomography-negative group, this group showed a statistically significant difference in the Mini-Mental State Examination recall score [2 (1 : 3) vs. 3 (2 : 3), P = .041] and single-photon emission computed tomography findings from the amyloid-negative group. In the mild cognitive impairment subgroup, correlations were found between amyloid deposition and single-photon emission computed tomography indicators, while in the subjective cognitive decline subgroup, only the Mini-Mental State Examination recall score correlated with amyloid deposition. Conclusion: The Mini-Mental State Examination recall score and single-photon emission computed tomography indicators may be worthwhile for further evaluation as predictors of amyloid deposition in the preclinical stage.

Clinical impact of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer's disease: a multicenter study.

OBJECTIVE: Amyloid positron emission tomography (PET) can reliably detect senile plaques and fluorinated ligands are approved for clinical use. However, the clinical impact of amyloid PET imaging is still under investigation. The aim of this study was to evaluate the diagnostic impact and clinical utility in patient management of amyloid PET using 18F-florbetapir in patients with cognitive impairment and suspected Alzheimer's disease (AD). We also aimed to determine the cutoffs for amyloid positivity for quantitative measures by investigating the agreement between quantitative and visual assessments. METHODS: Ninety-nine patients suspected of having AD underwent 18F-florbetapir PET at five institutions. Site-specialized physicians provided a diagnosis of AD or non-AD with a percentage estimate of their confidence and their plan for patient management in terms of medication, prescription dosage, additional diagnostic tests, and care planning both before and after receiving the amyloid imaging results. A PET image for each patient was visually assessed and dichotomously rated as either amyloid-positive or amyloid-negative by four board-certified nuclear medicine physicians. The PET images were also quantitatively analyzed using the standardized uptake value ratio (SUVR) and Centiloid (CL) scale. RESULTS: Visual interpretation obtained 48 positive and 51 negative PET scans. The amyloid PET results changed the AD and non-AD diagnosis in 39 of 99 patients (39.3%). The change rates of 26 of the 54 patients (48.1%) with a pre-scan AD diagnosis were significantly higher than those of 13 of the 45 patients with a pre-scan non-AD diagnosis (χ2 = 5.334, p = 0.0209). Amyloid PET results also resulted in at least one change to the patient management plan in 42 patients (42%), mainly medication (20 patients, 20%) and care planning (25 patients, 25%). Receiver-operating characteristic analysis determined the best agreement of the quantitative assessments and visual interpretation of PET scans to have an area under the curve of 0.993 at an SUVR of 1.19 and CL of 25.9. CONCLUSION: Amyloid PET using 18F-florbetapir PET had a substantial clinical impact on AD and non-AD diagnosis and on patient management by enhancing diagnostic confidence. In addition, the quantitative measures may improve the visual interpretation of amyloid positivity.

The Cingulate Island Sign is Useful for a Differential Diagnosis of Early-Onset Alzheimer's Disease and Dementia with Lewy Bodies: A 99mTc-ECD SPECT Study.

Introduction: Early-onset dementia is fast-progressing compared with late-onset dementia, with major clinical characteristics including prominent focal cerebral symptoms. Given its economic and psychological implications, proper diagnosis and treatment at an early stage is essential. In the present study, the authors conducted a retrospective study to evaluate the usefulness of various numerical indices (including CIScore calculated by eZIS, cerebral blood flow SPECT analysis software) in the differential diagnosis of early-onset dementia. Materials and Methods: This study involved patients with early-onset and mild dementia who were receiving ambulatory care at our outpatient department specializing in Alzheimer's disease (14 MCI patients, 16 AD patients, and 16 probable/possible DLB patients). ROC analysis was performed for each SVA numerical index calculated by eZIS to calculate AUC. For the AD and DLB groups, correlation between the CIScore and MMSE was assessed. Results: When SVA-A (severity) was used to differentiate AD from MCI and DLB from MCI, the respective AUC values were 0.960 and 0.911. When CIScore was used to differentiate AD from DLB (threshold value: 0.225), the obtained AUC value was 0.941, and the accuracy, sensitivity, and specificity were 90.6%, 87.5%, and 93.7%, respectively. No significant correlation was observed between the MMSE and CIScore scores in these disease groups. Conclusion: The results of this study have suggested that the SVA-A is a useful index for evaluating the conversion from MCI to either early-onset AD or DLB, and that the CIScore is useful for differentiating AD from DLB in both late-onset and early-onset dementia cases.

Genetic association between RAGE polymorphisms and Alzheimer's disease and Lewy body dementias in a Japanese cohort: a case-control study.

BACKGROUND/AIMS: Interaction of receptor for advanced glycation end products (RAGE) with amyloid-ß increases amplification of oxidative stress and plays pathological roles in Alzheimer's disease (AD). Oxidative stress leads to α-synuclein aggregation and is also a major contributing factor in the pathogenesis of Lewy body dementias (LBDs). Therefore, we aimed to investigate whether RAGE gene polymorphisms were associated with AD and LBDs. METHODS: Four single nucleotide polymorphisms (SNPs)-rs1800624, rs1800625, rs184003, and rs2070600-of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBDs patients, and 105 age-matched controls. RESULTS: Linkage disequilibrium (LD) examination showed strong LD from rs1800624 to rs2070600 on the gene (1.1 kb) in our cases in Japan. Rs184003 was associated with an increased risk of AD. Although there were no statistical associations for the other three SNPs, haplotypic analyses detected genetic associations between AD and the RAGE gene. Although relatively few cases were studied, results from the SNPs showed that they did not modify the risk of developing LBDs in the Japanese population. CONCLUSION: Our findings suggested that polymorphisms in the RAGE gene are involved in genetic susceptibility to AD. Copyright © 2016 John Wiley & Sons, Ltd.

Genetic Association between Presenilin 2 Polymorphisms and Alzheimer's Disease and Dementia of Lewy Body Type in a Japanese Population.

BACKGROUND/AIMS: Mutations in the presenilin 2 (PSEN2) gene cause familial Alzheimer's disease (AD). Common polymorphisms affect gene activity and increase the risk of AD. Nonsynonymous polymorphisms in the PSEN2 gene showed Lewy body dementia (LBD) phenotypes clinically. Therefore, we aimed to investigate whether PSEN2 gene polymorphisms were associated with AD or LBD. METHODS: Seven single nucleotide polymorphisms (SNPs) of the gene were analyzed using a case-control study design comprising 288 AD patients, 76 LBD patients, and 105 age-matched controls. RESULTS: Linkage disequilibrium (LD) examination showed strong LD from rs1295645 to rs8383 on the gene in our cases from Japan. There were no associations between the SNPs studied here and AD onset, and haplotypic analyses did not detect genetic associations between AD and the PSEN2 gene. Although the number of the cases was small, the SNPs studied did not modify the risk of developing LBD in a Japanese population. CONCLUSION: The common SNPs of the PSEN2 gene did not affect the risk of AD or LBD in a Japanese population. Because genetic variability of the PSEN2 gene is associated with behavioral and psychological symptoms of dementia (BPSD) in AD and LBD, further detailed analyses considering BPSD of both diseases would be required.

Genetic Association Between KIBRA Polymorphism and Alzheimer's Disease with in a Japanese Population.

KIBRA plays an important role in synaptic plasticity in human hippocampus related to cognitive function. Functional studies suggest that KIBRA is a potential candidate gene for memory and Alzheimer's disease (AD) risk. A single nucleotide polymorphism, Rs17070145 C allele affects the onset of AD in an age-dependent manner comparing with T/T genotypes and is also associated with risk of substance abuse and relapse. The aim of this case-control study was to investigate whether the rs17070145 polymorphism affected the onset of AD in an age-dependent manner in a Japanese population. We analysed KIBRA and APOE genotypes in 237 young AD cases, 154 age-matched control cases and 160 old AD cases. The analyses were performed by stratifying alcohol consumption and the APOE status. We used single photon emission computed tomography (SPECT) to analyse patients with AD with the rs17070145 polymorphism. The genotypic and allelic frequencies of the young AD group differed significantly from those of control and old AD groups. There was a significant association among high alcohol consumption (HAC-AD group) and the genotypic and allelic frequencies of the rs17070145 polymorphism. Logistic regression analyses demonstrate synergism between the APOE genotype and the rs17070145 C allele to increase the risk of AD in the young group; this was confirmed in the HAC-AD group. The SPECT study revealed hyperperfusion in the C allele carrier group was detected in the right inferior frontal gyrus compared with the T/T group. KIBRA rs17070145 affects specific phenotypes of patients with AD.