Effects of vitamin D supplementation on cognitive function and blood Aß-related biomarkers in older adults with Alzheimer's disease: a randomised, double-blind, placebo-controlled trial.

OBJECTIVE: Our study aimed to assess the effect of a 12-month vitamin D supplementation on cognitive function and amyloid beta (Aß)-related biomarkers in subjects with Alzheimer's disease (AD). METHODS : This was a randomised, double-blind, placebo-controlled trial. 210 AD patients were randomly divided into intervention and control groups. Participants received 12-month 800 IU/day of vitamin D or starch granules as placebo. Tests of cognitive performance and Aß-related biomarkers were measured at baseline, 6 months and 12 months. RESULTS : Repeated-measures analysis of variance showed significant improvements in plasma Aß42, APP, BACE1, APPmRNA, BACE1mRNA (p<0.001) levels and information, arithmetic, digit span, vocabulary, block design and picture arrange scores (p<0.05) in the intervention group over the control group. According to mixed-model analysis, vitamin D group had significant increase in full scale IQ during follow-up period (p<0.001). CONCLUSIONS: Daily oral vitamin D supplementation (800 IU/day) for 12 months may improve cognitive function and decrease Aß-related biomarkers in elderly patients with AD. Larger scale longer term randomised trials of vitamin D are needed. TRIAL REGISTRATION NUMBER: ChiCTR-IIR-16009549.

DHA supplementation improves cognitive function via enhancing Aß-mediated autophagy in Chinese elderly with mild cognitive impairment: a randomised placebo-controlled trial.

BACKGROUND: Higher docosahexaenoic acid (DHA) intake is inversely correlated with relative risk of Alzheimer's disease. The potential benefits of DHA supplementation in people with mild cognitive impairment (MCI) have not been fully examined. OBJECTIVE: Our study aimed to assess the effect of a 24-month DHA supplementation on cognitive function and amyloid beta (Aß)-mediated autophagy in elderly subjects with MCI. METHODS: This was a randomised, double-blind, placebo-controlled trial in Tianjin, China. A total of 240 individuals with MCI were identified and randomly divided into intervention (DHA 2 g/day, n=120) and control (corn oil as placebo, n=120) groups. Cognitive function and blood Aß-related biomarkers were measured at baseline, 6, 12, 18 and 24 months. Data were analysed using generalised estimating equation. RESULTS: A total of 217 participants (DHA: 109, placebo: 108) completed the trial. During the follow-up, scores of full-scale IQ, verbal IQ and subdomains of information and digit span were significantly higher in the intervention group than the convention group (p<0.05). In the intervention group, blood Aß-42 level and expression of Aß protein precursor mRNA were decreased (p<0.05), while Beclin-1 and LC3-II levels and expression of LC3-II mRNA were increased (p<0.05). CONCLUSION: Daily oral DHA supplementation (2 g/day) for 24 months may improve cognitive function and change blood biomarker-related Aß-mediated autophagy in people with MCI. Larger longer-term confirmatory studies are warranted. TRIAL REGISTRATION NUMBER: ChiCTR-IOR-15006058.

Effects of DHA Supplementation on Hippocampal Volume and Cognitive Function in Older Adults with Mild Cognitive Impairment: A 12-Month Randomized, Double-Blind, Placebo-Controlled Trial.

Docosahexaenoic acid (DHA) is important for brain function, and higher DHA intake is inversely correlated with relative risk of Alzheimer's disease. The potential benefits of DHA supplementation in people with mild cognitive impairment (MCI) have not been fully examined. Our study aimed to determine the effect of DHA supplementation on cognitive function and hippocampal atrophy in elderly subjects with MCI. This was a randomized, double-blind, placebo-controlled trial in Tianjin, China. 240 individuals with MCI aged 65 years and over were recruited and equalized randomly allocated to the DHA or the placebo group. Participants received 12-month DHA supplementation (2 g/day) or corn oil as placebo. Both global and specific subdomains of cognitive function and hippocampal volume were measured at baseline, 6 months, and 12 months. Both changes were analyzed by repeated-measure analysis of variance (ANOVA). This trial has been registered: ChiCTR-IOR-15006058. A total of 219 participants (DHA: 110, Placebo: 109) completed the trial. The change in mean serum DHA levels was greater in the intervention group (+3.85%) compared to the control group (+1.06%). Repeated-measures analyses of covariance showed that, over 12 months, there was a significant difference in the Full-Scale Intelligence Quotient (ηp2 = 0.084; p = 0.039), Information (ηp2 = 0.439; p = 0.000), and Digit Span (ηp2 = 0.375; p = 0.000) between DHA-treated versus the placebo group. In addition, there were significant differences in volumes of left hippocampus (ηp2 = 0.121, p = 0.016), right hippocampus (ηp2 = 0.757, p = 0.008), total hippocampus (ηp2 = 0.124, p = 0.023), and global cerebrum (ηp2 = 0.145, p = 0.032) between the two groups. These findings suggest that DHA supplementation (2 g/day) for 12 months in MCI subjects can significantly improve cognitive function and slow the progression of hippocampal atrophy. Larger, longer-term confirmatory studies are warranted.

The prevalence of mild cognitive impairment with type 2 diabetes mellitus among elderly people in China: A cross-sectional study.

BACKGROUND: In absence of curative treatments for dementia with type 2 diabetes mellitus (T2DM), mild cognitive impairment (MCI) in T2DM, the preclinical transitional states of dementia with T2DM has attracted dramatic attention. Our study was to estimate the prevalence and distribution of MCI in T2DM subjects from China, and identify influencing factors of subjects in MCI with T2DM. METHODS: In the present study, we performed cluster random sampling of 8213 people aged 65 years and older in Tianjin, a metropolitan city, located in northern China. All participants were interviewed and screened for T2DM. 1109 subjects with T2DM were initially screened with American Diabetes Association criteria for diagnosis of diabetes mellitus and were diagnosed with MCI and dementia according to the criteria of DSM-IIIR. The prevalence of MCI and dementia in subjects with T2DM were compared with that in ordinary subjects. Logistic regression analyses were performed to evaluate risk of MCI with T2DM. RESULTS: Among all 8213 subjects, overall MCI and dementia with T2DM prevalence were 13.5% and 2.34%, respectively. Compared with ordinary subjects, the prevalence of MCI in the present study was more frequent than the prevalence of MCI for the general population in almost each age group. In the univariate analyses, among all diabetic subjects, compared with cognitive intactly subjects, MCI subjects had significantly higher levels of age, current smoking, mean waist circumference, duration from onset of diabetes, insulin intake, systolic BP, fasting plasma glucose (FPG), glycosylated hemoglobin (HbA1c) and immunoreactive insulin (IRI). In multivariate logistic regression analyses, variables including current smoking, duration from onset of diabetes, FPG, HbA1c and IRI were significantly associated with increased risk for MCI with T2DM, the ORs were 1.36,1.33,1.17,1.25 and 1.33, respectively (all P<0.05). CONCLUSIONS: The present study confirms the high prevalence of MCI with T2DM among the elderly population of China. T2DM is related to a higher risk of MCI in a population with a high prevalence of this disorder and may aggravate the clinical picture as a concomitant factor.

The characteristic of cognitive function in Type 2 diabetes mellitus.

AIM: To identify characteristics of neuropsychological function among elderly individuals with Type 2 diabetes mellitus with mild cognitive impairment (T2DM-MCI) and evaluate domain-specific effects of T2DM on cognition. METHODS: This was a cross-sectional study conducted in Tianjin, China. MCI subjects (n=246) and controls were identified in elderly individuals with diabetes, and groups were matched in a 1:1 ratio for sex, age and educational level. Cognitive function was assessed using WAIS-III (block design, digit span), Trail Making Test A, Trail Making Test B, WMS-III (word list learning, logical memory), verbal fluency and MMSE. We used multivariable logistic regression to find diabetic factors associated with MCI. RESULTS: The mean MMSE score was 22.73 ± 2.32 in subjects with T2DM-MCI, versus 26.71 ± 2.43 in subjects cognitive normal (P<0.001). Executive and visuospatial functions were more impaired in individuals with T2DM-MCI than in those without, as assessed using block design (P<0.001), digit span test (P<0.001), and Trails B (P<0.001). For memory, subjects with T2DM-MCI did worse than those cognitive normal on the word learning list delayed recall (P=0.015). Diabetic-related factors such as longer duration of T2DM, higher HbA1c, insulin treatment was associated with a lower level of cognitive functioning using MMSE, block design, delayed recall and Trails B test. CONCLUSIONS: T2DM should be considered a risk factor for MCI. This risk may be associated with duration of diabetes, use of glucose-lowering medications, degree of glucose control. To decrease risk of MCI, it is important to monitor glucose control and adjust medications appropriately in elderly patients.

Conversion of mild cognitive impairment to dementia among subjects with diabetes: a population-based study of incidence and risk factors with five years of follow-up.

Type 2 diabetes mellitus (T2DM) is associated with dementia. Mild cognitive impairment (MCI) is a key determinant in this association. It is not clear whether T2DM increases the risk of conversion from MCI to dementia. We plan to explore the relationship between T2DM-MCI and dementia and identify its potential risk factors. A prospective community-based cohort study was conducted from March 2010 to March 2014, including 634 participants with T2DM-MCI, 261 T2DM participants who were cognitively intact, and 585 MCI participants without diabetes. All cohort members received detailed annual evaluations to detect dementia onset during the 5 years of follow-up. The three cohorts were compared to assess differences in dementia onset. Furthermore, Cox proportional hazards regression was used to identify risk factors for dementia onset in the T2DM-MCI cohort. During follow-up, 152 and 49 subjects developed dementia in the MCI and cognitively-intact cohorts, amounting to an adjusted hazard ratio (HR) of 1.66 (95% CI 1.07-2.26). In a survival analysis of the cohorts, MCI accelerated the median progression to dementia by 2.74 years. In a multivariable analysis of the T2DM-MCI cohort, major risk factors for dementia were age >75 years and longer durations of diabetes, while significantly reduced risks of dementia were associated with oral hypoglycemic agents and HMG-CoA reductase inhibitors. Insulin was not associated with significantly changed risk. T2DM-MCI may aggravate the clinical picture as a concomitant factor. To minimize progression to dementia, it may be worthwhile to target several modifiable diabetes-specific features, such as the duration of disease, glycemic control, and antidiabetic agents.

Association between apolipoprotein E ε4 and longitudinal cognitive decline: nested case-control study among chinese community-dwelling elders.

BACKGROUND/AIMS: Cognitive decline in the elderly is an early predictor of dementia. The apolipoprotein E (APOE) ε4 allele is considered an important genetic determinant of Alzheimer's disease (AD), and strongly suspected to play a role in cognitive variation. However, its effects upon predicting the progression of cognitive decline more generally remain unclear. Our aim was to explore the role of APOE ε4 in longitudinal cognitive decline, considering sociodemographics, vascular disease, and lipid profile. METHODS: We chose a nested case-control design, and prospectively collected demographic and clinical data, determined APOE genotypes, and obtained follow-up information on cognitive variation (measured by a spectrum of cognitive tests) for 3 years. Cognitive decline was predefined as an increase in Clinical Dementia Rating Scale class, or at least a 4-point decrease (>1 SD) in MMSE, between baseline and follow-ups. RESULTS: Among 600 follow-up subjects with mild cognitive impairment and aged 65 years or older, 114 pairs of cognitive decline and stable subjects were identified and matched for sex, age, and educational level in a 1:1 ratio. The APOE ε4 frequency in the cognitive decline group was significantly higher than that in the stable group (p < 0.05), while the APOE ε2 and ε3 prevalence in the cognitive decline group did not differ significantly from that in controls (p > 0.05). At the first follow-up, modest but significant declines only in the memory domain were associated with APOE ε4. At the last follow-up, significant associations were noted between APOE ε4 and cognitive decline from 5 of the 6 cognitive outcomes, which included story recall, memory, spatial recognition, naming, and sustained attention. Conditional logistic regression showed that the presence of APOE ε4 was significantly associated with the cognitive decline group, as compared to the stable group, adjusting for vascular diseases and lipid profile. CONCLUSIONS: APOE ε4 offered information on the risk of cognitive decline in this longitudinal study, and may exert detectable effects early in a long prodromal AD trajectory.

Prenatal and perinatal risk factors for autism in China.

We conducted a case-control study using 190 Han children with and without autism to investigate prenatal and perinatal risk factors for autism in China. Cases were recruited through public special education schools and controls from regular public schools in the same region (Tianjin), with frequency matching on sex and birth year. Unadjusted analyses identified seven prenatal and seven perinatal risk factors significantly associated with autism. In the adjusted analysis, nine risk factors showed significant association with autism: maternal second-hand smoke exposure, maternal chronic or acute medical conditions unrelated to pregnancy, maternal unhappy emotional state, gestational complications, edema, abnormal gestational age (<35 or >42 weeks), nuchal cord, gravidity >1, and advanced paternal age at delivery (>30 year-old).