Association between the catechol-O-methyltransferase polymorphism Val158Met and Alzheimer's disease in a Japanese population.

OBJECTIVE: Catechol-O-methyltransferase (COMT) plays an important role in dopamine degradation, which is associated with the pathophysiology of Alzheimer's disease (AD) and alcoholism. A functional COMT polymorphism, Val158Met (rs4680 G > A), affects the onset of AD and is associated with alcohol dependence through dopamine receptor sensitivity in the prefrontal cortex. METHODS: The aim of this case-control study (398 cases and 149 controls) was to investigate whether Val158Met polymorphism influences the onset of AD stratified according to alcohol consumption and apolipoprotein E (APOE) status. We also used single photon-emission computed tomography (SPECT) to analyse 26 patients with AD with the polymorphism. RESULTS: As a function of APOE status, the genotypic frequencies of rs4680 in patients with AD did not differ from those in controls. We detected a significant association between high alcohol consumption in patients with AD (HAC-AD group) and the polymorphism in genotypic and allelic frequencies. Logistic regression analyses demonstrated that the presence of the APOE genotype with rs4680 increased the risk for HAC-AD synergistically. Hyperperfusion in the right sub-lobar insula of patients with the G/G genotype was found compared with that of patients with the G/A genotype. SPECT studies showed a relationship between the polymorphism and compensatory reactions for dysfunctions of dopaminergic neurotransmission in AD pathophysiology. CONCLUSION: Although genetic association between the polymorphism and the onset of AD in a Japanese population were not observed, the polymorphism affected the risk for HAC-AD.

Polymorphisms in the aldehyde dehydrogenase 2 and dopamine ß hydroxylase genes are not associated with Alzheimer's disease.

Since ethanol and its metabolite, acetaldehyde, are directly neurotoxic, alcohol intake could affect the development of Alzheimer's disease (AD). Mitochondrial aldehyde dehydrogenase 2 (ALDH2) metabolizes acetaldehyde into acetate and also protects against oxidative stress, playing an important role in the development of AD. The activity of dopamine ß hydroxylase (DBH) is reduced in the hippocampus and neocortex in the AD brain. DBH is also involved in the pathophysiology of alcoholism. The aim of this study was to investigate whether polymorphisms of both ALDH2 and DBH genes were associated with AD. ALDH2*2 and two functional single nucleotide polymorphisms (SNPs) of the DBH gene were analyzed using a case-control study design. Our case-control data set consisted of 201 AD patients and 130 age-matched controls. We also analyzed stratifying by alcohol consumption and apolipoprotein E (APOE) genotypes. There were no associations between the SNPs studied here and the onset of AD. No synergetic associations were found among the SNPs, APOE and the risk for AD. Although high alcohol consumption AD (HAC-AD) patients were analyzed in detail, the current three SNPs were not related with HAC-AD. ALDH2*2 and functional SNPs of the DBH gene did not modify the risk for AD. Since our data set was constructed only with AD in a Japanese population, further detailed genetic analyses with other ethnic groups would be needed.

Changes in Mini-Mental State Examination score in Alzheimer's disease patients after stopping habitual drinking.

BACKGROUND: Globally, Alzheimer's disease (AD) is becoming an increasing problem as the population ages, and the effects of lifestyle factors on cognitive decline need to be better understood. This study examined the effects of alcohol abstinence on cognitive decline in AD. METHODS: Cognitive function after alcohol abstinence was retrospectively reviewed in AD patients (high and low alcohol consumption groups) and then compared with an alcohol-naïve AD group. The alcohol-naïve AD group included 18 outpatients with no history of habitual drinking. The alcohol-abstinence AD group included 20 outpatients who stopped drinking after their diagnoses. The latter group was classified into high and low groups depending on the amount of they drank before abstinence. Cognitive function was evaluated with the Mini-Mental State Examination at baseline, 6 months, and 12 months. For statistical analyses, a repeated measures, two-factor anova and post-hoc multiple comparisons were performed using the Bonferroni method. RESULTS: There was a significant effect of time on Mini-Mental State Examination score, but there was no difference in the baseline scores of the alcohol-naïve and alcohol-abstinence AD groups. The score was significantly lower at 6 and 12 months than at baseline in the alcohol-naïve group, but no significant difference was seen in the alcohol-abstinence group. There was a significant interaction between time and alcohol consumption subgroup on the score, with no difference in baseline score between the low and high consumption groups. The score was significantly lower only in the high consumption group at 12 months. CONCLUSIONS : In AD patients with a history of habitual drinking, abstinence was effective for reducing cognitive decline during the clinical course. However, such an effect was not seen in patients who had consumed high amounts of alcohol before diagnosis of AD.

Benefits of use, and tolerance of, medium-chain triglyceride medical food in the management of Japanese patients with Alzheimer's disease: a prospective, open-label pilot study.

OBJECTIVES: This is the first clinical trial of this type in Japan, designed to analyze two important aspects of Alzheimer's disease (AD) management using medium-chain triglycerides. Axona was administered for 3 months (40 g of powder containing 20 g of caprylic triglycerides). We used an indurating, four-step dose-titration method (from 10 to 40 g per day) for 7 days before the trial, and examined the tolerance and adverse effects of this intervention. We also investigated its effect on cognitive function in mild-to-moderate AD patients. PATIENTS AND METHODS: This was a clinical intervention in 22 Japanese patients with sporadic AD at a mild-to-moderate stage (ten females, 12 males), mean age (± standard deviation) 63.9 (±8.5) years, Mini-Mental State Examination (MMSE) score, 10-25, seven patients were ApoE4-positive. During Axona administration, we examined changes in cognitive function by obtaining MMSE and AD assessment-scale scores. Intolerance and serum ketone concentrations were also examined. RESULTS: The tolerance of Axona was good, without severe gastrointestinal adverse effects. Axona did not improve cognitive function in our sample of AD patients, even in those patients without the ApoE4 allele. However, some ApoE4-negative patients with baseline MMSE score ≥14 showed improvement in their cognitive functions. CONCLUSION: The modified dose-titration method, starting with a low dose of Axona, decreased gastrointestinal adverse effects in Japanese patients. Axona might be effective for some relatively mildly affected patients with AD (with cognitive function MMSE score of ≥14 and lacking the ApoE4 allele).