| 1. |
- Georgakis, Marios K., et al.
(författare)
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Age at menopause and duration of reproductive period in association with dementia and cognitive function : A systematic review and meta-analysis
- 2016
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 73, s. 224-243
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Forskningsöversikt (refereegranskat)abstract
- Introduction: The preponderance of dementia among postmenopausal women compared with same-age men and the female sex hormones neuroprotective properties support a tentative role of their deficiency in the dementia pathogenesis. Methods: Pairs of independent reviewers screened 12,323 publications derived from a search strategy for MEDLINE to identify articles investigating the association of age at menopause/reproductive period with (i) dementia and (ii) cognitive function; a snowball of eligible articles and reviews was conducted and authors were contacted for additional information. Random-effect models were used for the meta analysis. Results: Age at menopause (13 studies; 19,449 participants) and reproductive period (4 studies; 9916 participants) in the highest categories were not associated with odds of dementia (effect size [ES]: 0.97 [0.78-1.21]) and Alzheimer's disease (ES: 1.06 [0.71-1.58]). Significant heterogeneity was however noted in both analyses (12: 63.3%, p = 0.003 and 12: 72.6%, p = 0.01, respectively). Subgroup analyses by outcome assessment, study design, level of adjustment and study quality did not materially change the findings. In 9/13 studies assessing cognitive function, advanced age at menopause/longer reproductive period was significantly associated with better cognitive performance/lower decline. Due to statistical differences, no meta-analysis was possible for cognitive function. Conclusions: Existing evidence does not support an association between indices of prolonged exposure to female hormones and lower dementia risk. There are indications, however, for better cognitive performance and delayed cognitive decline, supporting a link between female hormone deficiency and cognitive aging. Current literature limitations, indicated by the heterogeneous study-set, point towards research priorities in this clinically relevant area.
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| 2. |
- Georgakis, Marios K, et al.
(författare)
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Association of Age at Menopause and Duration of Reproductive Period With Depression After Menopause : A Systematic Review and Meta-analysis
- 2016
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Ingår i: JAMA psychiatry. - : American Medical Association (AMA). - 2168-6238 .- 2168-622X. ; 73:2, s. 139-149
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Forskningsöversikt (refereegranskat)abstract
- Importance: Estrogens have neuroprotective and antidepressive effects; however, associations between indices of reduced endogenous estrogens and risk for postmenopausal depression have not been systematically explored.Objective: To investigate the association of age at menopause and the duration of the reproductive period with the risk for depression among postmenopausal women with naturally occurring menopause.Data Sources: A search strategy for use of MEDLINE was developed (through January 1, 2015) using the key terms menopause, climacteric, reproductive period, depression, and mood disorders. References of included studies and reviews were also screened; authors were contacted to maximize synthesized evidence.Study Selection: A total of 12 323 articles, without language restriction, were screened by pairs of reviewers to identify observational studies related to the study hypothesis; 14 studies were eligible for meta-analysis.Data Extraction and Synthesis: Pairs of reviewers independently extracted information on study design and type of analysis by participants' characteristics and methods of depression ascertainment. Study quality was assessed using the Newcastle-Ottawa Scale, and fixed- or random-effects models were implemented.Main Outcomes and Measures: Pooled-effect estimates for depression, defined by psychiatric evaluation or validated instruments, by age at menopause and duration of the reproductive period.Results: The 14 studies included in the meta-analysis represented 67 714 women. An inverse association (reported as odds ratio [OR]; 95% CI of 2-year increments) with depression in postmenopausal women was shown for increasing age at menopause (0.98; 0.96-0.99 [67 434 unique participants; 13 studies]) and duration of the reproductive period (0.98; 0.96-0.99 [54 715 unique participants; 5 studies]). Menopause at age 40 or more years compared with premature menopause was associated with a 50% decreased risk for depression (3033 unique participants; 4 studies). Pooling of studies examining severe depression showed a 5% decrease in risk of severe depression with increasing (2-year increment) age at menopause (52 736 unique participants; 3 studies); sensitivity analysis of studies controlling for past depression revealed similar results for age at menopause (0.98; 0.96-1.00 [48 894 unique participants; 3 studies). No heterogeneity or publication bias was evident in the main analyses.Conclusions and Relevance: Longer exposure to endogenous estrogens, expressed as older age at menopause and longer reproductive period, is associated with a lower risk of depression in later life. Identifying women at higher risk for depression due to early menopause who could benefit from psychiatric intervention or estrogen-based therapies could be useful in the clinical setting.
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| 3. |
- Georgakis, Marios K, et al.
(författare)
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Comorbidity of Cognitive Impairment and Late-Life Depression Increase Mortality : Results From a Cohort of Community-Dwelling Elderly Individuals in Rural Greece
- 2016
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Ingår i: Journal of Geriatric Psychiatry and Neurology. - : SAGE Publications. - 0891-9887 .- 1552-5708. ; 29:4, s. 195-204
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Tidskriftsartikel (refereegranskat)abstract
- OBJECTIVE: To investigate the association of cognitive impairment (COGI) and depression with all-cause mortality and cardiovascular-specific mortality among community-dwelling elderly individuals in rural Greece.METHODS: Cognition and depressive symptomatology of 676 Velestino town residents aged ≥60 years were assessed using Mini-Mental State Examination (MMSE) and Geriatric Depression Scale (GDS), respectively. Eight-year all-cause mortality and cardiovascular mortality were explored by multivariate Cox regression models controlling for major confounders.RESULTS: Two hundred and one patients died during follow-up. Cognitive impairment (MMSE ≤ 23) was independently associated with all-cause mortality (hazard ratio [HR]: 1.57, 95% confidence interval [CI]: 1.13-2.18) and cardiovascular mortality (HR: 1.57, 95%CI: 1.03-2.41). Moderate to severe depression (GDS > 10) was significantly associated only with a 51% increase in all-cause mortality. A male-specific association was noted for moderate to severe depression, whereas the effect of COGI was limited to females. Noteworthy, COGI and depression comorbidity, rather than their sole presence, increased all-cause mortality and cardiovascular mortality by 66% and 72%, respectively. The mortality effect of COGI was augmented among patients with depression and of depression among patients with COGI.CONCLUSION: COGI and depression, 2 entities often coexisting among elderly individuals, appear to increase all-cause mortality and cardiovascular mortality. Gender-specific modes may prevail but their comorbidity should be carefully assessed, as it seems to represent an independent index of increased frailty, which eventually shortens life expectancy.
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| 4. |
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| 5. |
- Georgakis, Marios K., et al.
(författare)
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Surgical menopause in association with cognitive function and risk of dementia : A systematic review and meta-analysis
- 2019
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Ingår i: Psychoneuroendocrinology. - : PERGAMON-ELSEVIER SCIENCE LTD. - 0306-4530 .- 1873-3360. ; 106, s. 9-19
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Forskningsöversikt (refereegranskat)abstract
- Introduction: Experimental and epidemiological studies suggest female sex hormones to have long-lasting neuroprotective and anti-ageing properties. Surgically-induced menopause leads to a premature cessation of exposure to female sex hormones and could thus impact late-life cognitive function. Yet, evidence remains controversial. Methods: We systematically reviewed literature for articles investigating the association of surgical menopause (defined as bilateral oophorectomy before the onset of menopause) with risk of dementia, cognitive performance, cognitive decline, and Alzheimer's disease neuropathological indices later in life. We evaluated study quality with the Newcastle-Ottawa scale and performed random-effects meta-analyses. Results: We identified 11 eligible studies (N = 18,867). Although surgical menopause at any age was not associated with risk of dementia (4 studies; HR: 1.16, 95%CI: 0.96-1.43), early surgical menopause (<= 45 years of age) was associated with a statistically significantly higher risk (2 studies; HR: 1.70, 95%CI: 1.07-2.69). Surgical menopause at any age was associated with faster decline in verbal memory, semantic memory, and processing speed, whereas early surgical menopause was further associated with faster global cognitive decline. No heterogeneity was noted. Among women undergoing surgical menopause, a younger age at surgery was associated with faster decline in global cognition, semantic and episodic memory, worse performance in verbal fluency and executive function, and accumulation of Alzheimer's neuropathology. Conclusions: Current evidence is limited, but suggests surgical menopause induced by bilateral oophorectomy at <= 45 years of age to be associated with higher risk of dementia and cognitive decline. Additional large-scale cohort studies are necessary to replicate these findings.
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| 6. |
- Georgakis, Marios K., et al.
(författare)
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Validation of TICS for detection of dementia and mild cognitive impairment among individuals characterized by low levels of education or illiteracy : a population-based study in rural Greece
- 2017
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Ingår i: Clinical Neuropsychologist (Neuropsychology, Development and Cognition. - : Informa UK Limited. - 1385-4046 .- 1744-4144. ; 31, s. 61-71
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Tidskriftsartikel (refereegranskat)abstract
- Objective: The efficacy of the most widely used tests for dementia screening is limited in populations characterized by low levels of education. This study aimed to validate the face-to-face administered Telephone Interview for Cognitive Status (TICS) for detection of dementia and mild cognitive impairment (MCI) in a population-based sample of community dwelling individuals characterized by low levels of education or illiteracy in rural Greece. Methods: The translated Greek version of TICS was administered through face-to-face interview in 133 elderly residents of Velestino of low educational level (<12years). We assessed its internal consistency and test-retest reliability, its correlation with sociodemographic parameters, and its discriminant ability for cognitive impairment and dementia, as defined by a brief neurological evaluation, including assessment of cognitive status and level of independence. Results: TICS was characterized by adequate internal consistency (Cronbach's : .72) and very high test-retest reliability (intra-class correlation coefficient: .93); it was positively correlated with age and educational years. MCI and dementia were diagnosed in 18 and 10.5% of the population, respectively. Its discriminant ability for detection of dementia was high (Area under the curve, AUC: .85), with a sensitivity and specificity of 86 and 82%, respectively, at a cut-off point of 24/25. TICS did not perform well in differentiating MCI from cognitively normal individuals though (AUC: .67). Conclusion: The directly administered TICS questionnaire provides an easily applicable and brief option for detection of dementia in populations of low educational level and might be useful in the context of both clinical and research purposes.
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| 7. |
- Karalexi, Maria A., et al.
(författare)
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Gender-affirming hormone treatment and cognitive function in transgender young adults : a systematic review and meta-analysis
- 2020
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Ingår i: Psychoneuroendocrinology. - : Elsevier BV. - 0306-4530 .- 1873-3360. ; 119
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Forskningsöversikt (refereegranskat)abstract
- Background: Previous studies have examined whether steroid hormone treatment in transgender individuals may affect cognitive function; yet, their limited power does not allow firm conclusions to be drawn. We leveraged data from to-date literature aiming to explore the effect of gender-affirming hormone administration on cognitive function in transgender individuals.Methods: A search strategy of MEDLINE was developed (through June 1, 2019) using the key terms transgender, hormone therapy and cognitive function. Eligible were (i) cohort studies examining the longitudinal effect of hormone therapy on cognition, and (ii) cross-sectional studies comparing the cognitive function between treated and non-treated individuals. Standardized mean differences (Hedges' g) were pooled using random-effects models. Study quality was evaluated using the Newcastle-Ottawa Scale.Outcomes: Ten studies (seven cohort and three cross-sectional) were eligible representing 234 birth-assigned males (aM) and 150 birth-assigned females (aF). The synthesis of cohort studies (n = 5) for visuospatial ability following hormone treatment showed a statistically significant enhancement among aF (g = 0.55, 95% confidence intervals [CI]: 0.29, 0.82) and an improvement with a trend towards statistical significance among aM (g = 0.28, 95%CI: -0.01, 0.58). By contrast, no adverse effects of hormone administration were shown. No heterogeneity was evident in most meta-analyses.Interpretation: Current evidence does not support an adverse impact of hormone therapy on cognitive function, whereas a statistically significant enhancing effect on visuospatial ability was shown in aF. New longitudinal studies with longer follow-up should explore the long-term effects of hormone therapy, especially the effects on younger individuals, where there is greater scarcity of data.
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| 8. |
- Petridou, Eleni Th., et al.
(författare)
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Advanced parental age as risk factor for childhood acute lymphoblastic leukemia : results from studies of the Childhood Leukemia International Consortium
- 2018
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Ingår i: European Journal of Epidemiology. - : SPRINGER. - 0393-2990 .- 1573-7284. ; 33:10, s. 965-976
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Tidskriftsartikel (refereegranskat)abstract
- Advanced parental age has been associated with adverse health effects in the offspring including childhood (0-14 years) acute lymphoblastic leukemia (ALL), as reported in our meta-analysis of published studies. We aimed to further explore the association using primary data from 16 studies participating in the Childhood Leukemia International Consortium. Data were contributed by 11 case-control (CC) studies (7919 cases and 12,942 controls recruited via interviews) and five nested case-control (NCC) studies (8801 cases and 29,690 controls identified through record linkage of population-based health registries) with variable enrollment periods (1968-2015). Five-year paternal and maternal age increments were introduced in two meta-analyses by study design using adjusted odds ratios (OR) derived from each study. Increased paternal age was associated with greater ALL risk in the offspring (ORCC 1.05, 95% CI 1.00-1.11; ORNCC 1.04, 95% CI 1.01-1.07). A similar positive association with advanced maternal age was observed only in the NCC results (ORCC 0.99, 95% CI 0.91-1.07, heterogeneity I (2) = 58%, p = 0.002; ORNCC 1.05, 95% CI 1.01-1.08). The positive association between parental age and risk of ALL was most marked among children aged 1-5 years and remained unchanged following mutual adjustment for the collinear effect of the paternal and maternal age variables; analyses of the relatively small numbers of discordant paternal-maternal age pairs were not fully enlightening. Our results strengthen the evidence that advanced parental age is associated with increased childhood ALL risk; collinearity of maternal with paternal age complicates causal interpretation. Employing datasets with cytogenetic information may further elucidate involvement of each parental component and clarify underlying mechanisms.
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