Chiine Kodama

Relationship between Delusions and Regional Cerebral Blood Flow in Alzheimer’s Disease

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.

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

The results of previous reports estimating the prevalence of mild cognitive impairment (MCI) have varied widely according to the criteria used to define MCI.

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.

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

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.

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.

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.

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

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.

Association among depression, apolipoprotein E4 allele, mild cognitive impairment and conversion to dementia in a Japanese community

Background: The metabolic syndrome is reported to have detrimental effects on cognition. However, this association may depend upon sex and age and may be modulated by inflammation in distinct populations. Therefore, we investigated the association between metabolic syndrome and cognitive functioning in a population of middle-aged and older men and the impact of inflammatory responses. Methods: This community-based, cross-sectional study included 3,369 men aged 40-79 years from eight centres enrolled in the European Male Ageing Study (EMAS). Cognitive function was assessed using the Rey-Osterrieth Complex Figure (ROCF) test, the Camden Topographical Recognition Memory (CTRM) test and the Digit Symbol Substitution Test (DSST). Metabolic syndrome was defined by the National Cholesterol Education Program’s ATP-III criteria. Serum high sensitivity C-reactive protein (hs-CRP) levels were determined by solid-phase, chemiluminescent immunoassay. Associations between cognitive performance and metabolic syndrome and the influence of hs-CRP were explored using linear regression models. Results: Complete cognitive and metabolic syndrome data from 3152 subjects were included in the analysis, of which 1007 (32%) fulfilled the criteria for metabolic syndrome. There was no significant associations between cognitive scores and metabolic syndrome after adjustment for putative health and lifestyle confounders. However, analysis of the individual factors revealed an inverse association between glucose levels and cognition. Hs-CRP levels did not modulate cognitive performance. Conclusions: We found no independent associations between the presence of the metabolic syndrome and cognitive function in a representative sample of community-dwelling, middle-aged and older European men. Hs-CRP levels were not associated with cognitive performance either, regardless of the presence or absence of the metabolic syndrome. Of the individual components of the metabolic syndrome, only hyperglycaemia was associated with poorer cognitive performance. These findings suggest that a dysregulated carbohydrate metabolism is associated with lower cognitive function but the nature of this relationship requires further investigation.

Longitudinal Regional Cerebral Blood Flow Change Due to Normal Aging: A Community-Based Study

Background: Although there are several studies which explore the aging effect on regional cerebral blood flow (rCBF) using single-photon emission computed tomography (SPECT), most of studies are cross-sectional study and they have not considered the partial volume effect. Partial volume effect correction (PVC) is necessary to evaluate the rCBF accurately. In this study, we evaluated the longitudinal rCBF change due to normal aging with and without PVC. Methods: Subject are 78 healthy cognitively normal subjects (34 males and 44 females, mean(SD): 72(4.3)). Their average MMSE score was 28.4 at baseline. With the hypothesis that different age range of the subjects might show different rate in volume reduction or cerebral perfusion, the subjects were divided into three groups (under 69, 70-74, and over 75 years old). All of the subjects underwent three-dimensional T1 weighted MRI and Tc-99m ECD SPECT twice, at baseline and 3-years follow-up. MR images were segmented into grey matter, white matter, and cerebral-spinal fluid using SPM5. Using the grey matter and white matter images, partial volume correction was performed on the SPECT images. Paired t-tests were performed on the grey matter images, the SPECT images with PVC, and the SPECT images without PVC to evaluate the aging effect on rCBF and how PVC will affect the result. Results: Subjects under 69 years old showed cortical volume reduction due to aging in prefrontal, orbital frontal, cingulate, medial temporal regions, and parietal lobules. The analysis with nonPVC SPECT revealed the similar reduced perfusion regions as cortical volume reduction. On the other hand, the analysis with PVC SPECT confined the reduced perfusion regions to the posterior cingulate and orbital frontal gyrus. Subjects over 70 years old did not show any significant volume or perfusion reduction due to normal aging. Conclusions: Our results suggest that normal aging cause the perfusion reduction in the limited regions, and posterior cingulate cortex is susceptible to the even normal aging effect. It is also speculated that the cortical reduction or cerebral perfusion reduction rate might get slower in the cognitively intact subjects over 70 years old.