ApoE4 is not associated with depression when mild cognitive impairment is considered.

OBJECTIVE: The aim of the study was to examine the relationship between apolipoprotein E4 allele (ApoE4) and depression among an older Japanese population. Mild cognitive impairment (MCI) was taken into consideration. METHODS: This is a community-based cross-sectional study. We assessed the mood and cognitive function of Japanese community-dwelling individuals aged 65 years or older. In the first phase of the study, we evaluated the mood and cognitive function. In the second phase, face-to-face structured interviews were conducted. Individuals with dementia and other mental diseases were excluded on the basis of a consensus meeting of psychiatrists and neuropsychologists; 738 subjects with full data were included in the analyses. We subdivided depression into major depressive episode (MDE) and depressive symptoms cases (DSCs). DSC was defined as a score of 6 or more on the Geriatric Depression Scale but not having a diagnosis of MDE. The relationship between depression (MDE and DSC) and ApoE4 was examined by multivariate logistic regression. RESULTS: The adjusted odds ratio (OR) of ApoE4 on DSC was not significant (OR = 0.82, 95%CI = 0.48-1.39, p < 0.46). Sex (OR = 2.53, 95%CI = 1.33-4.79, p < 0.01), MCI (1.95, 1.21-3.14, p < 0.01), years of education (0.87, 0.79-0.95, p < 0.01), and Nishimura's activities of daily living scores (0.75, 0.63-0.89, p < 0.01) significantly correlated with prevalence of DSC. There were no significant risk factors for MDE. CONCLUSION: Apolipoprotein E4 allele contributed to neither DSC nor MDE. The association of MCI with ApoE4 and DSC suggested that MCI is a confounder for the association between ApoE4 and DSC.

Combination of antioxidant supplements improved cognitive function in the elderly.

Although nutrients or agents with antioxidant properties were reported to show a preventive effect on cognitive decline in animal studies, epidemiologic data on select antioxidants have shown conflicting results. We investigated whether a combination of antioxidants from supplements is effective for the improvement of cognitive function of elderly. Forty-one subjects from a community dwelling aged 65 years and older took supplements containing n-3 polyunsaturated fatty acids (n-3 PUFA), lycopene, and Ginkgo biloba extracts (GE) daily for 3 years. The data of 622 subjects without supplement intake were used as control. We investigated the changes in cognitive function during a 3-year follow-up. We also investigated the influence of apolipoprotein E (APOE) genotype on the effect of antioxidants. We found that a combination of antioxidants improved cognitive function of aged persons after 3 years. Our present study also indicated this improvement in cognitive function with supplement intake in both APOE4 non-carrier (E4-) and APOE4 carrier (E4+) groups. Especially, in E4+, we found a large effect size of the improvement of cognition. When multiple antioxidants are used in combination, they protect against vulnerability to other agents and synergistically potentiate their antioxidant properties. These synergistically potentiated antioxidant effects of agents contribute to the improvement of cognitive function.

Effect of plasma lipids, hypertension and APOE genotype on cognitive decline.

We examined the combined effect of plasma lipids/hypertension and apolipoprotein E (APOE) genotype on cognitive function in elderly individuals. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC), APOE, and history of hypertension were evaluated in 622 community-dwelling individuals aged 65 years and older. We investigated the associations between plasma lipids/hypertension and cognitive function in apolipoprotein E4 allele (APOE4) carrier (E4+) and APOE4 noncarrier (E4-) groups using 3-year longitudinal data. At baseline and 3 years later, cognitive scores were correlated with plasma APOE levels in both E4- and E4+, and HDL level in E4-. The combination of hypertension and E4+, but not E4-, was associated with a significant deterioration in cognitive function during the 3-year follow-up. Our findings suggest that an interaction between APOE and HDL is facilitated by APOE4, and is possibly linked with a protective effect on cognitive decline in later life. The findings also indicate a synergistic effect of an APOE4 allele and hypertension on the acceleration of cognitive decline.

Association between cognitive function and plasma lipids of the elderly after controlling for apolipoprotein E genotype.

OBJECTIVE: Although the relationship between cognitive function and plasma lipids has attracted attention, previous studies have shown conflicting results. One possible confounding factor is due to the influence of gene-related modulator. We investigated the relationship between cognitive function and lipid plasma levels of old age after controlling for apolipoprotein E (APOE) genotype. METHODS: One thousand three hundred ninety-five subjects without dementia age 65 and older participated in this study. They were divided into two groups, with and without APOE4 [E4 (+) and E4 (-)]. Plasma concentrations of high-density lipoprotein (HDL), low-density lipoprotein (LDL), triglyceride (TG), total cholesterol (TC) and apolipoprotein E (apoE) were measured. Associations between plasma concentrations of lipids and cognitive function were investigated for each group. RESULTS: We found a positive association between cognitive scores and plasma apoE level in both E4 (-) and E4 (+) groups. A positive relationship was also observed between cognitive score and HDL level in the E4 (-) group, but not in the E4 (+) group. No substantial association between cognitive score and LDL, TG, and TC levels was found in either of the groups. CONCLUSIONS: Our findings suggest that plasma apoE have a positive influence on cognitive function in both E4 (-) and E4 (+) groups, whereas the positive influence of plasma HDL was shown only in E4 (-) group. The identification of the influences of (APOE) genotype and the intracellular linkage among apoE and HDL metabolism is hoped for new preventive and therapeutic strategies for cognitive change of elderly.

Prevalence of depression and depressive symptoms among older Japanese people: comorbidity of mild cognitive impairment and depression.

BACKGROUND: The aim of the study was to estimate the prevalence of DSM-III-R major depressive episodes (MDEs), depressive symptoms cases (DSCs) (defined as a score of ≥6 on the Geriatric Depression Scale but falling short of MDE), and coexisting mild cognitive impairment (MCI) among Japanese community-dwelling older people. METHODS: Prevalence was estimated based on screening evaluation, individual interviews, and door-to-door visits. MDE and DSC were diagnosed, and the cognitive status of the participants was determined to be dementia, MCI, or normal. RESULTS: A total of 1888 subjects of 2698 candidates (70.0%) participated. The prevalence of MDE and DSC were estimated to be 4.5% (95% CI, 3.4-6.0) and 11.5% (95% CI, 4.2-28.0), respectively. MCI was more prevalent in subjects with depression (26.2%) than those with normal mood (17.9%). Although no prototypical profile of cognitive dysfunction was revealed, multiple MCI was more prevalent in subjects with depression (12.2%) than subjects with normal mood (3.8%). Conversely, subjects with MCI (26.3%) were more likely to develop depression compared with those with normal cognitive function (18.0%). CONCLUSIONS: The prevalence of depression in our subjects seems to be similar with that of previous studies. MCI was more prevalent in subjects with depression than those with normal mood. Individuals with depression showed no particular association with any of the four MCIs. Given that depression and MCI are often associated with each other and that MCI is a predictor for development of dementia, the risk of developing dementia in the depressed older people with coexisting MCI should be acknowledged.

Prevalence of four subtypes of mild cognitive impairment and APOE in a Japanese community.

BACKGROUND: The results of previous reports estimating the prevalence of mild cognitive impairment (MCI) have varied widely according to the criteria used to define MCI. METHODS: We assessed the cognitive function of Japanese community-dwelling individuals >or=65 years old and attempted to estimate the prevalence of four MCI subtypes (amnestic single, amnestic multiple, nonamnestic single, and nonamnestic multiple) using two cutoffs (1 and 1.5 SD) below normative standard. Presence of apolipoprotein E4 allele (APOE4), which is known as a strong risk factor for AD, is reportedly associated with high risk of conversion from MCI to AD. We therefore calculated the frequency of APOE4 carriers for each MCI subtype. RESULTS: Initially 1888 (70%) of 2698 baseline samples participated, and 1433 (53%) subjects who had complete clinical data including APOE typing remained for the final analysis. The prevalence of MCI subtypes varied within the range of 1.7-16.6%, depending on the criteria applied. Prevalence of MCI was higher using a cutoff at -1.0 SD than at -1.5 SD, and prevalence of amnestic MCI single at -1.5 SD was lowest among all subtypes of MCI. Frequency of APOE4 was higher for amnestic MCI than for non-amnestic MCI or the cognitively normal group. CONCLUSION: The prevalence of MCI was highly dependent on the diagnostic criteria applied. A higher frequency of APOE4 in participants with amnestic MCI subtype suggested a greater risk of future AD. For future interventions to delay the onset of dementia, targeting individuals with amnestic MCI multiple at -1 SD might be desirable.

Dementia and mild cognitive impairment among non-responders to a community survey.

We aimed to estimate the prevalence of mild cognitive impairment (MCI) among elderly non-responders to a community-based survey. We conducted a two-phase, population-based cross-sectional study of community-dwelling individuals aged 65 years or older in Tone, located in central Japan. The first phase of the study consisted of physical and cognitive examinations of individuals who responded to the first recruitment (quick-responders), whereas the second phase included individuals who did not respond in the first phase (delayed-responders). We compared the prevalence of MCI and dementia between delayed-responders and quick-responders. Of the 2,698 potential candidates, 1,888 (1,619 quick-responders, 225 delayed-responders, and 44 nursing home residents) were enrolled (70.0%). The prevalence of MCI was 2.3-fold increased in delayed-responders compared to the quick-responders (OR=2.27, 95% CI: 1.37-3.77, p=0.002, aged< or =74). In order to develop a method for the early detection of dementia, we must pay more attention to delayed-or non-responders.

Relationship between delusions and regional cerebral blood flow in Alzheimer's disease.

UNLABELLED: To investigate the association between delusions and cerebral functional deficits in Alzheimer's disease (AD), we evaluated probable AD patients with and without delusions. METHODS: Functional brain imaging was performed by single photon emission computed tomography with technetium-99m-labeled ethyl cysteinate dimer (99mTc-ECD) in 64 AD patients and 76 age-matched normal healthy volunteers. SPECT data were analyzed by statistical parametric mapping. RESULTS: In AD patients, no differences were found in age and cognitive activities between those with (n = 25) and without (n = 39) delusions. Compared with normal healthy volunteers, AD patients had significantly decreased perfusion in the posterior cingulate gyri, precunei, and parietal association cortex. Moreover, in the patients with delusions, perfusion was significantly decreased in the frontal lobe with right side dominance. In the comparison between the patients with and without delusions, the patients with delusions had significantly decreased perfusion in the prefrontal cortex, anterior cingulate gyri, inferior to middle temporal cortices, and parietal cortex of the right hemisphere (p < 0.01). CONCLUSION: The functional deficits in the right hemisphere may be the cause of delusions in AD.