Ghrelin improves cognition via activation of the cAMP- CREB signalling pathway in depressed male C57BL/6J mice.

BACKGROUND: Depression leads to a cognitive decline and decreases in ghrelin are observed in depression. Ghrelin affects the level of Brain-derived nerve growth factor (BDNF) through the cAMP-CREB signalling pathway, and lower BDNF levels lead to cognitive decline. Therefore, it is reasonable to assume that in depression, lower ghrelin causes a decrease in BDNF levels and cognitive decline though the cAMP- CREB signalling pathway. METHODS: A total of 120 C57BL/6J male mice were randomly divided into six groups of 20 mice: non-depression groups (sham group, ghrelin group, and ghrelin + (D-lys3)-GHRP-6 group) and depression groups (depression group, depression + ghrelin group and depression + ghrelin + (D-lys3)-GHRP group). A depression mouse model was established by injecting normal saline, ghrelin or ghrelin + (D-lys3) -GHRP-6 into the lateral ventricle of each group. Cognition, hippocampal long-term potentiation (LTP), ghrelin mRNA and protein level, BDNF level and CREB level in the hippocampus were detected. RESULTS: In the depression mouse model groups, all comparison indexes (cognition and hippocampal levels of LTP, ghrelin mRNA and proteins, and BDNF and CREB) had significant negative changes. In the mice with depression, ghrelin or ghrelin + (D-lys3)-GHRP-6 was injected, and all the comparison indicators showed significant positive changes. Supplementation of ghrelin+(D-lys3))-GHRP-6 resulted in more significant positive changes in all comparison indexes than those of ghrelin alone. CONCLUSIONS: In the depression model, lower ghrelin causes hippocampal BDNF to decrease and results in cognitive decline via the cAMP-CREB signalling pathway.

The polymorphism of ARNTL2 (BMAL2) gene rs2306074 C>T is associated with susceptibility of Alzheimer disease in Chinese population.

In the present study, we investigated whether polymorphism of ARNTL2 (BMAL2) gene rs2306074 T/C was associated with susceptibility of Alzheimer disease (AD) in Chinese population. A case-control method was employed in this study. 296 unrelated AD patients and 423 control subjects were recruited in current study. The prevalence of C carriers in BMAL2 gene rs2306074 T/C in AD patients was significantly higher than that of control subjects in both the whole sample and APOE ε 4 non-carriers (in the whole sample: χ (2) = 5.938, P = 0.012; in APOE ε 4 non-carriers: χ (2) = 9.048, P < 0.0001). In addition, both in the whole sample and APOE ε 4 non-carriers, prevalence of CC genotypes in BMAL2 gene rs2306074 of AD patients was also significantly higher than that in controls (in the whole sample: χ (2) = 5.126, P = 0.018; in APOE ε 4 non-carriers: χ (2) = 7.389, P = 0.023). However, there was no significant difference of prevalence of C carriers and CC genotypes in BMAL2 gene rs2306074 T/C between AD patients and control subjects among APOE ε 4 carriers (C carriers: χ (2) = 0.020, P = 0.900; CC genotypes: χ (2) = 0.017, P = 0.946). C carriers in BMAL2 gene rs2306074 T/C are associated with a high susceptibility of AD among APOE ε 4 non-carriers but not among APOE ε 4 carriers in Chinese population.

Cigarette smoking is associated with increased diastolic blood pressure among Chinese nonagenarians/centenarians.

OBJECTIVE: Cigarette smoking has been confirmed as a factor influencing arterial blood pressure. In the present study, we studied whether cigarette smoking habits were still associated with arterial blood pressure among Chinese nonagenarians/centenarians. METHODS: The present study analyzed data from a survey conducted on all residents aged 90 years or more in the DuJiangYan district (in total 2,311,709 inhabitants) in 2005. RESULTS: The individuals included in the statistical analysis were 216 men and 445 women. Individuals who were heavy smokers (76.62 ± 13.28 mmHg) had higher diastolic blood pressure, compared with medium and light smokers (72.33 ± 12.98 and 70.28 ± 10.31 mmHg) (F = 3.551, p = 0.030). There was a higher prevalence of diastolic hypertension (21.62% vs 5.75% and 7.14%, χ(2 =) 6.302, p = 0.043). Furthermore, there was a higher risk for diastolic hypertension in heavy smokers (OR = 3.886, 95% CI 1.241-12.161) (adjusted) compared with medium (OR = 1.475, 95% CI 0.599-3.360) and light smokers (1.00 reference). There was, however, no significant difference in systolic blood pressure or prevalence of systolic hypertension among the different smoking groups. CONCLUSIONS: In summary, we found that among Chinese nonagenarians/centenarians, heavy smoking (current or former) could increase diastolic blood pressure and prevalence of diastolic hypertension, but was not associated with changes in systolic blood pressure.

Hypothalamic-pituitary-thyroid axis in patients with Alzheimer disease (AD).

OBJECTIVE: We observed the function of hypothalamic-pituitary-thyroid axis in patients with Alzheimer disease (AD) using a case-control study. METHODS: The case was a cohort that included 50 patients with AD. For each case subject, 1 control who was of similar age, sex, daily activities (scale of Lawton), sleep quality (Pittsburgh Sleep Quality Index), and depression (15-item Geriatrics Depression Scale) was recruited. Thyrotropin-releasing hormone (TRH), thyroid-stimulating hormone (TSH), total triiodothyronine (TT3), total tetraiodothyronine (TT4), free triiodothyronine (FT3), and free tetraiodothyronine (FT4) were detected using radioimmunity. RESULTS: Compared with the healthy controls, the patients with AD had significantly lower levels of TRH (67.72 ± 18.44 vs 78.64 ± 14.31 pmol/L; t = 2.078; P = 0.036), TSH (3.89 ± 1.22 vs 4.31 ± 1.07 mIU/L; t = 2.331; P = 0.024), TT3 (1.44 ± 0.21 vs 1.63 ± 0.19 nmol/L; t = 3.761; P = 0.018), TT4 (119.71 ± 18.64 nmol/L vs 129.54 ± 23.17 nmol/L; t = 1.328; P = 0.044), FT3 (4.01 ± 1.27 vs 5.41 ± 0.99 pmol/L; t = 4.976; P = 0.008), and FT4 (9.84 ± 1.56 vs 12.96 ± 2.20 pmol/L; t = 5.381; P = 0.006). In the AD cases, none of the correlations between TRH and TSH, TT3, TT4, FT3, and FT4, and between TSH and TT3, TT4, FT3, FT4 was significant. However, in the healthy controls, TRH was significantly correlated with TSH (R = 0.020; P = 0.042) and FT4 (R = 0.015; P = 0.018), and TSH was significantly correlated with TT4 (R = 0.209; P = 0.017) and FT4 (R = 0.215; P = 0.009). CONCLUSION: Alzheimer disease was associated with abnormal function of the hypothalamic-pituitary-thyroid axis.

Association of serum lipid/lipoprotein with Pro12Ala polymorphism in PPAR-γ2 among Chinese nonagenarians/centenarians.

BACKGROUND AND AIMS: In previous studies, the Pro12Ala polymorphism in the peroxisome proliferator-activated receptor gamma 2 (PPAR-γ2) was shown to be associated with both lipid metabolism and longevity. We examined whether the polymorphism continued to be associated with abnormal levels of serum lipid/lipoprotein among elderly subjects (≥90 years). METHODS: The Pro12Ala variant was examined using polymerase chain reaction restriction fragment length polymorphism (PCR-RFLP). Abnormal levels of serum lipid/lipoprotein were defined according to the criteria provided by the Chinese Medical Association (2004). Abnormal criteria were triglyceride (TG) >5.18 mmol/l, total cholesterol (TC) >1.7 mmol/l, low-density lipoprotein cholesterol (LDL-C) >3.37 mmol/l and high-density lipoprotein cholesterol (HDL-C) <1.04 mmol/l). RESULTS: The sample included 673 unrelated Chinese individuals aged 90-108 years (mean age: 93.54 ± 3.54 years) and 67.3% females. Genotype frequencies of the Pro12Ala polymorphism were 0% Ala12Ala, 8.9% Pro12Ala, 91.1% Pro12Pro. Neither differences in the levels of serum lipid/lipoprotein nor the prevalence of their abnormal levels was significant between subjects who were or were not 12Ala carriers. Unadjusted and adjusted multiple logistic regressions showed that the odds ratios (OR) for abnormal levels of serum lipid/lipoprotein were not associated with the Pro12Ala polymorphism in PPAR-γ2. CONCLUSIONS: Levels of serum lipid/lipoprotein were not associated with the Pro12Ala polymorphism in PPAR-γ2 among Chinese nonagenarians and centenarians, which was different from the general population.

Education and risk for late life depression: a meta-analysis of published literature.

OBJECTIVE: Less education is commonly viewed as an important risk factor for late life depression. However, this has still not been confirmed. The goal of this study was to determine the relationship between education and risk for depression among the old. METHOD: MEDLINE, EMBASE, and The Cochrane Library database were used to identify potential studies. The studies were divided into cross-sectional and longitudinal subsets. The qualitative meta-analysis of cross-sectional studies and that of longitudinal studies were preformed, respectively. For prevalence and incidence rates of depression, odds risk (OR) and relative risk (RR) were calculated, respectively. RESULTS: Twenty-four cross-sectional and 12 prospective longitudinal studies were included in this review. In this meta-analysis, in the more and less education groups, there were 22,964 and 28,024 subjects and 3032 and 6462 cases of depression, respectively. The qualitative meta-analysis showed that, compared with old people with more education, those with less education had higher risk for depression (odds risk (OR): 1.58, 95% confidence intervals (95% CI): 1.38-1.82; Relative risk (RR): 1.49, 95% CI: 1.16-1.91). CONCLUSIONS: Despite the methodological limitations of this meta-analysis, less education is associated with increase risk of late life depression.

Cognitive impairment and depression among Chinese nonagenarians/centenarians.

PURPOSE: In this study, we explored the association between cognitive impairment and depression in the very elderly using a sample aged 90-108 years. METHODS: A cross-sectional study. RESULTS: The sample included 682 unrelated Chinese nonagenarians/centenarians (67.25% women, mean age of 93.49 years). The mean depression score (measured with the brief 23-item Geriatrics Depression Scale-Chinese Edition was 8.45 (standard deviation [SD] = 3.30). The mean of cognitive function scores (measured with the 30-item Mini-Mental State Examination) was 15.54 (SD = 5.38). There was no significant difference in cognitive function scores between subjects with and without depression, and there was also no significant difference in depression scores between subjects with and without cognitive impairment. There was also no significant difference in the frequency of depression between subjects with and without cognitive impairment or in the frequency of cognitive impairment between subjects with and without depression. Both the odds ratio (OR) of depression (as a function of increased cognitive impairment) and the OR of cognitive impairment (as a function of increased depression) were found to be insignificant. Pearson Correlation also showed no significant correlation between depression scores and cognitive function scores. CONCLUSIONS: In summary, we found that depression was not directly correlated with cognitive impairment in Chinese nonagenarians and centenarians.

Health status and risk for depression among the elderly: a meta-analysis of published literature.

OBJECTIVE: the goal of this study was to determine the relationship between health status, including self-rated health status and chronic disease, and risk for depression among the elderly. METHOD: MEDLINE, EMBASE and The Cochrane Library Database were used to identify potential studies. The studies were classified into cross-sectional and longitudinal subsets. For each study, the numbers of the total participants, cases (for cross-sectional study) or incident cases (for longitudinal study) of depression in each health status group were extracted and entered into Review Manager 4.2. The quantitative meta-analysis of cross-sectional studies and that of longitudinal studies were performed, respectively. For prevalence and incidence rates of depression, odds risk and relative risk (RR) were calculated, respectively. RESULTS: the quantitative meta-analysis showed that, compared with the elderly without chronic disease, those with chronic disease had higher risk for depression (RR: 1.53, 95% confidence intervals (CI): 1.20-1.97). Compared with the elderly with good self-rated health, those with poor self-rated health had higher risk for depression (RR: 2.40, 95% CI: 1.94-2.97). CONCLUSIONS: despite the methodological limitations of this meta-analysis, both poor self-rated health status and the presence of chronic disease are risk factors for depression among the elderly. In the elderly, poor self-reported health status appears to be more strongly associated with depression than the presence of chronic disease.

Collaborative care interventions for depression in the elderly: a systematic review of randomized controlled trials.

OBJECTIVE: To determine the effective components and the feasibility of collaborative care interventions (CCIs) in the treatment of depression in older patients. METHODS: Systematic review of randomized controlled trials, in which CCIs were used to manage depression in patients aged 60 or older. RESULTS: We identified 3 randomized controlled trials involving 3930 participants, 2757 of whom received CCIs and the others received usual care. Collaborative care interventions were more effective in improving depression symptoms than usual care during each follow-up period. Compared with baseline, thoughts of suicide in subjects receiving CCIs significantly decreased (odds Ratio [OR], 0.52; 95% confidence intervals [CI], 0.35-0.77), but not that in those receiving usual care (OR, 0.85; 95% CI, 0.50-1.43). Subjects receiving CCIs were significantly more likely to report depression treatment (including any antidepressant medication and psychotherapy) than those receiving usual care during each follow-up period. Collaborative care interventions significantly increased depression-free days, but did not significantly increase outpatient cost. At 6 and 12 months postintervention, compared with those receiving usual care, participants receiving CCIs had lower levels of depression symptoms and thoughts of suicide. Moreover, participants receiving CCIs were significantly more likely to report antidepressant medication treatment, but were not significantly more likely to report psychotherapy. Collaborative care interventions with communication between primary care providers and mental health providers were no more effective in improving depression symptoms than CCIs without such communication. CONCLUSIONS: Collaborative care interventions are more effective for depression in older people than usual care and are also of high value. Antidepressant medication is a definitely effective component of CCIs, but communication between primary care providers and mental health providers seems not to be an effective component of CCIs. The effect of psychotherapy in CCIs should be further explored.