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1.
Artigo em Inglês | MEDLINE | ID: mdl-32396611

RESUMO

We aimed to examine the relationship between APOE*4 carriage on cognitive decline, and whether these associations were moderated by sex, baseline age, ethnicity, and vascular risk factors. Participants were 19,225 individuals aged 54-103 years from 15 longitudinal cohort studies with a mean follow up duration ranging between 1.2 and 10.7 years. Two-step individual participant data (IPD) meta-analysis was used to pool results of study-wise analyses predicting memory and general cognitive decline from carriage of one or two APOE*4 alleles, and moderation of these associations by age, sex, vascular risk factors and ethnicity. Separate pooled estimates were calculated in both men and women who were younger (i.e., 62 years) and older (i.e., 80 years) at baseline. Results showed that APOE*4 carriage was related to faster general cognitive decline in women, and faster memory decline in men. A stronger dose-dependent effect was observed in older men, with faster general cognitive and memory decline in those carrying two versus one APOE*4 allele. Vascular risk factors were related to an increased effect of APOE*4 on memory decline in younger women, but a weaker effect of APOE*4 on general cognitive decline in older men. The relationship between APOE*4 carriage and memory decline was larger in older-aged Asians than Whites. In sum, APOE*4 is related to cognitive decline in men and women, although these effects are enhanced by age and carriage of two APOE*4 alleles in men, a higher numbers of vascular risk factors during the early stages of late adulthood in women, and Asian ethnicity.

3.
PLoS Med ; 16(7): e1002853, 2019 07.
Artigo em Inglês | MEDLINE | ID: mdl-31335910

RESUMO

BACKGROUND: With no effective treatments for cognitive decline or dementia, improving the evidence base for modifiable risk factors is a research priority. This study investigated associations between risk factors and late-life cognitive decline on a global scale, including comparisons between ethno-regional groups. METHODS AND FINDINGS: We harmonized longitudinal data from 20 population-based cohorts from 15 countries over 5 continents, including 48,522 individuals (58.4% women) aged 54-105 (mean = 72.7) years and without dementia at baseline. Studies had 2-15 years of follow-up. The risk factors investigated were age, sex, education, alcohol consumption, anxiety, apolipoprotein E ε4 allele (APOE*4) status, atrial fibrillation, blood pressure and pulse pressure, body mass index, cardiovascular disease, depression, diabetes, self-rated health, high cholesterol, hypertension, peripheral vascular disease, physical activity, smoking, and history of stroke. Associations with risk factors were determined for a global cognitive composite outcome (memory, language, processing speed, and executive functioning tests) and Mini-Mental State Examination score. Individual participant data meta-analyses of multivariable linear mixed model results pooled across cohorts revealed that for at least 1 cognitive outcome, age (B = -0.1, SE = 0.01), APOE*4 carriage (B = -0.31, SE = 0.11), depression (B = -0.11, SE = 0.06), diabetes (B = -0.23, SE = 0.10), current smoking (B = -0.20, SE = 0.08), and history of stroke (B = -0.22, SE = 0.09) were independently associated with poorer cognitive performance (p < 0.05 for all), and higher levels of education (B = 0.12, SE = 0.02) and vigorous physical activity (B = 0.17, SE = 0.06) were associated with better performance (p < 0.01 for both). Age (B = -0.07, SE = 0.01), APOE*4 carriage (B = -0.41, SE = 0.18), and diabetes (B = -0.18, SE = 0.10) were independently associated with faster cognitive decline (p < 0.05 for all). Different effects between Asian people and white people included stronger associations for Asian people between ever smoking and poorer cognition (group by risk factor interaction: B = -0.24, SE = 0.12), and between diabetes and cognitive decline (B = -0.66, SE = 0.27; p < 0.05 for both). Limitations of our study include a loss or distortion of risk factor data with harmonization, and not investigating factors at midlife. CONCLUSIONS: These results suggest that education, smoking, physical activity, diabetes, and stroke are all modifiable factors associated with cognitive decline. If these factors are determined to be causal, controlling them could minimize worldwide levels of cognitive decline. However, any global prevention strategy may need to consider ethno-regional differences.


Assuntos
Cognição , Disfunção Cognitiva/etnologia , Grupos Étnicos/psicologia , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/diagnóstico , Disfunção Cognitiva/psicologia , Comorbidade , Diabetes Mellitus/etnologia , Exercício Físico , Feminino , Educação em Saúde , Humanos , Masculino , Pessoa de Meia-Idade , Medição de Risco , Fatores de Risco , Fumar/efeitos adversos , Fumar/etnologia , Acidente Vascular Cerebral/etnologia
4.
Ageing Res Rev ; 54: 100935, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31326616

RESUMO

Frailty is a complex geriatric syndrome associated with biological vulnerability to stressors and decreased physiological reserve. Its etiology and pathogenesis are not completely understood, although various causes and complex pathways have been proposed. Immune system alterations (immunosenescence and "InflammAging") have been suggested to contribute to frailty, but a precise causative role of such alterations remains to be determined. Genetic studies support the suggestion of immune system involvement in frailty: genetic variants in genes involved in immune system function have been associated with the syndrome. Interestingly, nutritional status, through its effects on cellular metabolism, may also influence the immune system, i.e. hormone and cytokine (mainly adipocytokine) levels, and immune cell populations and function, increasing inflammation and contributing to frailty. This review aims to discuss the role of immune system alterations in frailty, analyzing the role of genetic factors in frailty onset and the impact of diet on inflammation and, in turn, on frailty.

6.
Biomed Res Int ; 2017: 3592359, 2017.
Artigo em Inglês | MEDLINE | ID: mdl-28393076

RESUMO

Estimates of depressive disorders in the elderly vary depending on how cases are defined. We estimated the prevalence of subthreshold depression (SD) and clinically significant depression (D) in a population of 70-74-year-olds. We also looked for associations with sociodemographic factors and perceptions of self. Participants underwent a multidimensional assessment (social, medical, and neuropsychological). The estimated prevalence of SD was 15.71% (95% CI: 13.70-17.72), while that of D was 5.58% (95% CI: 4.31-6.85). Multinomial logistic regression analysis revealed that female gender and dissatisfaction with family relationships were related to SD and D. A self-perception of physical age as older than actual age (but not comorbidity) and greater self-perceived stress caused by negative life events both increased the probability of SD. The likelihood of D was decreased in those who perceived their own health as good, whereas a self-perception of mental age as older than actual age and dissatisfaction with relationships with friends were both significantly associated with D. Both SD and D emerged as key problems in our population. Female gender and self-perceptions of various characteristics, which can be explored through simple questions, are associated with late-life depression in elderly people independently of their actual physical condition and other characteristics.


Assuntos
Transtorno Depressivo/epidemiologia , Transtorno Depressivo/fisiopatologia , Atividades Cotidianas , Idoso , Transtorno Depressivo/psicologia , Feminino , Humanos , Itália , Masculino , Fatores de Risco , Autoimagem , Fatores Sexuais
7.
PLoS Med ; 14(3): e1002261, 2017 Mar.
Artigo em Inglês | MEDLINE | ID: mdl-28323832

RESUMO

BACKGROUND: The prevalence of dementia varies around the world, potentially contributed to by international differences in rates of age-related cognitive decline. Our primary goal was to investigate how rates of age-related decline in cognitive test performance varied among international cohort studies of cognitive aging. We also determined the extent to which sex, educational attainment, and apolipoprotein E ε4 allele (APOE*4) carrier status were associated with decline. METHODS AND FINDINGS: We harmonized longitudinal data for 14 cohorts from 12 countries (Australia, Brazil, France, Greece, Hong Kong, Italy, Japan, Singapore, Spain, South Korea, United Kingdom, United States), for a total of 42,170 individuals aged 54-105 y (42% male), including 3.3% with dementia at baseline. The studies began between 1989 and 2011, with all but three ongoing, and each had 2-16 assessment waves (median = 3) and a follow-up duration of 2-15 y. We analyzed standardized Mini-Mental State Examination (MMSE) and memory, processing speed, language, and executive functioning test scores using linear mixed models, adjusted for sex and education, and meta-analytic techniques. Performance on all cognitive measures declined with age, with the most rapid rate of change pooled across cohorts a moderate -0.26 standard deviations per decade (SD/decade) (95% confidence interval [CI] [-0.35, -0.16], p < 0.001) for processing speed. Rates of decline accelerated slightly with age, with executive functioning showing the largest additional rate of decline with every further decade of age (-0.07 SD/decade, 95% CI [-0.10, -0.03], p = 0.002). There was a considerable degree of heterogeneity in the associations across cohorts, including a slightly faster decline (p = 0.021) on the MMSE for Asians (-0.20 SD/decade, 95% CI [-0.28, -0.12], p < 0.001) than for whites (-0.09 SD/decade, 95% CI [-0.16, -0.02], p = 0.009). Males declined on the MMSE at a slightly slower rate than females (difference = 0.023 SD/decade, 95% CI [0.011, 0.035], p < 0.001), and every additional year of education was associated with a rate of decline slightly slower for the MMSE (0.004 SD/decade less, 95% CI [0.002, 0.006], p = 0.001), but slightly faster for language (-0.007 SD/decade more, 95% CI [-0.011, -0.003], p = 0.001). APOE*4 carriers declined slightly more rapidly than non-carriers on most cognitive measures, with processing speed showing the greatest difference (-0.08 SD/decade, 95% CI [-0.15, -0.01], p = 0.019). The same overall pattern of results was found when analyses were repeated with baseline dementia cases excluded. We used only one test to represent cognitive domains, and though a prototypical one, we nevertheless urge caution in generalizing the results to domains rather than viewing them as test-specific associations. This study lacked cohorts from Africa, India, and mainland China. CONCLUSIONS: Cognitive performance declined with age, and more rapidly with increasing age, across samples from diverse ethnocultural groups and geographical regions. Associations varied across cohorts, suggesting that different rates of cognitive decline might contribute to the global variation in dementia prevalence. However, the many similarities and consistent associations with education and APOE genotype indicate a need to explore how international differences in associations with other risk factors such as genetics, cardiovascular health, and lifestyle are involved. Future studies should attempt to use multiple tests for each cognitive domain and feature populations from ethnocultural groups and geographical regions for which we lacked data.


Assuntos
Apolipoproteínas E/genética , Disfunção Cognitiva/epidemiologia , Escolaridade , Genótipo , Fatores Etários , Idoso , Idoso de 80 Anos ou mais , Disfunção Cognitiva/etiologia , Estudos de Coortes , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Fatores de Risco , Fatores Sexuais
9.
Exp Gerontol ; 76: 9-16, 2016 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-26774227

RESUMO

High total homocysteine (tHcy) is associated with cognitive impairment in the elderly. The impact of high tHcy on different cognitive domains deserves further investigation, as does the role of the C677T polymorphism of the 5,10 methylenetetrahydrofolate reductase (MTHFR) gene. A cross-sectional analysis of 903 subjects from the population-based "InveCe.Ab" study was performed. The participants had no psychosis or active neurological disorders. They underwent a neuropsychological assessment. Principal component analysis allowed cognitive performance to be condensed into two components: executive functions and memory. Novel components were evaluated for association with tHcy, controlling for potential confounders. Regression models showed that high serum tHcy was associated with lower executive functions, but not with memory. MTHFR C677T TT was associated with higher tHcy but did not affect cognitive performance per se. However, when combined with the apolipoprotein E (APOE)-ε4 allele, it was a risk factor for lower executive performance, independently of tHcy levels. In summary, high tHcy per se, or MTHFR C677T TT in combination with the APOE-ε4 allele, might be associated primarily with executive dysfunctions rather than memory loss.


Assuntos
Envelhecimento/genética , Apolipoproteínas E/genética , Transtornos Cognitivos/genética , Cognição , Epistasia Genética , Homocisteína/sangue , Hiper-Homocisteinemia/genética , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Fatores Etários , Idoso , Envelhecimento/sangue , Envelhecimento/psicologia , Biomarcadores/sangue , Transtornos Cognitivos/sangue , Transtornos Cognitivos/diagnóstico , Transtornos Cognitivos/psicologia , Estudos Transversais , Função Executiva , Feminino , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Avaliação Geriátrica , Humanos , Hiper-Homocisteinemia/sangue , Hiper-Homocisteinemia/diagnóstico , Hiper-Homocisteinemia/psicologia , Masculino , Memória , Testes Neuropsicológicos , Fenótipo , Análise de Componente Principal , Fatores de Risco , Regulação para Cima
10.
PLoS One ; 10(11): e0142388, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26539987

RESUMO

BACKGROUND: Changes in criteria and differences in populations studied and methodology have produced a wide range of prevalence estimates for mild cognitive impairment (MCI). METHODS: Uniform criteria were applied to harmonized data from 11 studies from USA, Europe, Asia and Australia, and MCI prevalence estimates determined using three separate definitions of cognitive impairment. RESULTS: The published range of MCI prevalence estimates was 5.0%-36.7%. This was reduced with all cognitive impairment definitions: performance in the bottom 6.681% (3.2%-10.8%); Clinical Dementia Rating of 0.5 (1.8%-14.9%); Mini-Mental State Examination score of 24-27 (2.1%-20.7%). Prevalences using the first definition were 5.9% overall, and increased with age (P < .001) but were unaffected by sex or the main races/ethnicities investigated (Whites and Chinese). Not completing high school increased the likelihood of MCI (P ≤ .01). CONCLUSION: Applying uniform criteria to harmonized data greatly reduced the variation in MCI prevalence internationally.


Assuntos
Disfunção Cognitiva/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Ásia/epidemiologia , Austrália/epidemiologia , Comportamento Cooperativo , Estudos Transversais , Demência/epidemiologia , Progressão da Doença , Europa (Continente)/epidemiologia , Feminino , Humanos , Estudos Longitudinais , Masculino , Pessoa de Meia-Idade , Testes Neuropsicológicos , Prevalência
11.
PLoS One ; 10(11): e0143395, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-26598970

RESUMO

BACKGROUND: Depression is common in the elderly. The role of genetic and environmental factors in modulating depressive symptoms is not clear. METHODS: We evaluated the influence of serotonin transporter gene polymorphisms and recent adverse life events on depressive symptoms in an elderly Italian population. We used data from "InveCe.Ab", a population-based study of 1321 subjects aged 70-74 years. We used the 15-item Geriatric Depression Scale (GDS) to assess depressive symptoms-a GDS score ≥5 points (GDS≥5) indicated the presence of clinically relevant symptoms-and performed 5-HTTLPR and rs25531 genotyping to obtain the triallelic polymorphism of the serotonin transporter. We used the Geriatric Adverse Life Events Scale to measure adverse life events, and logistic regression models to evaluate the role of genotype and recent adverse life events in depressive symptoms, controlling for potential confounders and independent predictors. RESULTS: Two hundred subjects (15.76%) had a GDS≥5. The 5-HTTLPR triallelic polymorphism was significantly associated with GDS≥5. Only S'S' carriers showed an increased risk of depressive symptoms (ORadj = 1.81, p = .022); one extra adverse life event increased this risk by 14% (p = .061) independently of genotype. Other factors significantly related to GDS≥5 were: female gender (ORadj = 2.49, p < .001), age (ORadj = 1.19, p = .007), a history of depression (ORadj = 4.73, p < .001), and comorbidity (ORadj = 1.23, p = .001). One extra adverse life event increased the risk of depressive symptoms by 57% (p = .005) only in the L'L' carriers, while antidepressant intake was directly related to GDS≥5 in the L'S' carriers (ORadj = 2.46, p = .036) and borderline significant in the S'S' carriers (ORadj = 2.41, p = .081). DISCUSSION: The S'S' genotype and recent exposure to adverse life events were independently associated with depressive symptoms. The S'S' genotype, compared with the environment, exerted a predominant effect on depressive symptoms, suggesting that it reduces the efficacy of antidepressant therapy. We conclude that genetics may be an important risk factor for depressive symptoms in late adulthood.


Assuntos
Depressão/genética , Predisposição Genética para Doença , Acontecimentos que Mudam a Vida , Polimorfismo Genético , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Idoso , Feminino , Humanos , Masculino
12.
Oncotarget ; 6(9): 6524-34, 2015 Mar 30.
Artigo em Inglês | MEDLINE | ID: mdl-25779661

RESUMO

Aims of this study were to investigate the ability of RACK1 pseudosubstrate alone or in combination with classical immune stimuli to activate human leukocytes, and to restore age-associated immune defects.A total of 25 donors (17 old donors, 77-79 yrs; 8 young donors, 25-34 yrs) were enrolled. To evaluate the effect of RACK1 pseudosubstrate on cytokine production and CD86 expression the whole blood assay was used. Cultures were treated with RACK1 pseudosubstrate in the presence or absence of lipopolysaccharide (LPS) or phytohaemagglutinin (PHA) and incubated for 24 h or 48 h for LPS-induced CD86 expression, TNF-α, IL-6, IL-8, IL-10 production, and PHA-induced IL-4, IL-10, IFN-γ, respectively. RACK1 pseudosubstrate alone induced IL-6, IL-8, and CD86 expression in both young and old donors, and IFN-γ in old donors. In combination with LPS an increase in IL-8, IL-10 and TNF-α was observed, also resulting in restoration of age-associated defective production, while no changes in the other parameters investigated were found.Even if based on a small sample size, these results suggest the possibility to by-pass some of age-associated immune alterations, which may be beneficial in situations were natural immune stimulation is required, and highlight a different role of PKCß in immune cells activation.


Assuntos
Adjuvantes Imunológicos/farmacologia , Envelhecimento/imunologia , Proteínas de Ligação ao GTP/metabolismo , Leucócitos/efeitos dos fármacos , Proteínas de Neoplasias/metabolismo , Fragmentos de Peptídeos/farmacologia , Proteína Quinase C beta/farmacologia , Receptores de Superfície Celular/metabolismo , Adulto , Fatores Etários , Idoso , Envelhecimento/metabolismo , Antígeno B7-2/imunologia , Antígeno B7-2/metabolismo , Linhagem Celular , Citocinas/imunologia , Citocinas/metabolismo , Endotoxinas/farmacologia , Ativação Enzimática , Feminino , Humanos , Leucócitos/enzimologia , Leucócitos/imunologia , Masculino , Fito-Hemaglutininas/farmacologia , Proteína Quinase C beta/metabolismo , Estrutura Terciária de Proteína , Receptores de Quinase C Ativada , Especificidade por Substrato , Fatores de Tempo
13.
Br J Pharmacol ; 172(11): 2918-27, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25626076

RESUMO

BACKGROUND AND PURPOSE: Dehydroepiandrosterone (DHEA) is thought to be an anti-glucocorticoid hormone known to be fully functional in young people but deficient in aged humans. Our previous data suggest that DHEA not only counteracts the effect of cortisol on RACK1 expression, a protein required both for the correct functioning of immune cells and for PKC-dependent pathway activation, but also modulates the inhibitory effect of cortisol on LPS-induced cytokine production. The purpose of this study was to investigate the effect of DHEA on the splicing mechanism of the human glucocorticoid receptor (GR). EXPERIMENTAL APPROACH: The THP1 monocytic cell line was used as a cellular model. Cytokine production was measured by specific elisa. Western blot and real-time RT-PCR were used, where appropriate, to determine the effect of DHEA on GRs, serine/arginine-rich proteins (SRp), and RACK1 protein and mRNA. Small-interfering RNA was used to down-regulate GRß. KEY RESULTS: DHEA induced a dose-related up-regulation of GRß and GRß knockdown completely prevented DHEA-induced RACK1 expression and modulation of cytokine release. Moreover, we showed that DHEA influenced the expression of some components of the SRps found within the spliceosome, the main regulators of the alternative splicing of the GR gene. CONCLUSIONS AND IMPLICATIONS: These data contribute to our understanding of the mechanism of action of DHEA and its effect on the immune system and as an anti-glucocorticoid agent.


Assuntos
Processamento Alternativo/efeitos dos fármacos , Desidroepiandrosterona/farmacologia , Proteínas de Ligação ao GTP/efeitos dos fármacos , Glucocorticoides/farmacologia , Hidrocortisona/farmacologia , Monócitos/efeitos dos fármacos , Proteínas de Neoplasias/efeitos dos fármacos , RNA Mensageiro/efeitos dos fármacos , Receptores de Superfície Celular/efeitos dos fármacos , Receptores de Glucocorticoides/efeitos dos fármacos , Corticosteroides/farmacologia , Linhagem Celular , Proteínas de Ligação ao GTP/genética , Proteínas de Ligação ao GTP/metabolismo , Técnicas de Silenciamento de Genes , Humanos , Interleucina-8/efeitos dos fármacos , Interleucina-8/metabolismo , Monócitos/metabolismo , Proteínas de Neoplasias/genética , Proteínas de Neoplasias/metabolismo , RNA Mensageiro/metabolismo , Receptores de Quinase C Ativada , Receptores de Superfície Celular/genética , Receptores de Superfície Celular/metabolismo , Receptores de Glucocorticoides/genética , Receptores de Glucocorticoides/metabolismo , Reação em Cadeia da Polimerase Via Transcriptase Reversa , Regulação para Cima/efeitos dos fármacos
14.
J Sleep Res ; 24(2): 215-22, 2015 Apr.
Artigo em Inglês | MEDLINE | ID: mdl-25297871

RESUMO

Previous studies have documented the involvement of the central nervous system serotonin in promoting wakefulness. There are few and conflicting results over whether there is an actual association between bearing the short allele of serotonin transporter promoter polymorphism (5-HTTLPR) and worse sleep quality. This study examined whether sleep onset latency complaint is associated with the 5-HTTLPR triallelic polymorphism in the SLC6A4 gene promoter and whether this polymorphism influences the relationship between sleep onset latency complaint and depressive symptoms in elderly people. A total of 1321 community-dwelling individuals aged 70-74 years were interviewed for sleep onset latency complaint and for sleep medication consumption. Participants' genomic DNA was typed for 5-HTTLPR and rs25531 polymorphisms. Depressive symptoms were evaluated with the Geriatric Depression Scale Short form and general medical comorbidity was assessed by the Cumulative Illness Rating Scale. The presence of a past history of depression was recorded. The S' allele of the 5-HTTLPR triallelic polymorphism was associated with sleep onset latency complaint. This association was maintained after adjusting for depressive symptoms, sex, age, history of depression and medical comorbidity. After stratification for 5-HTTLPR/rs25531, only in S'S' individuals high depressive symptoms were actually associated with sleep onset latency complaint. These data indicate that the low-expressing 5-HTTLPR triallelic polymorphism is an independent risk factor for sleep onset latency disturbance. Furthermore, the 5-HTTLPR genotype influences the association between depressive symptoms and sleep onset latency complaint.


Assuntos
Depressão/complicações , Depressão/genética , Polimorfismo Genético/genética , Proteínas da Membrana Plasmática de Transporte de Serotonina/genética , Transtornos do Sono-Vigília/genética , Idoso , Alelos , Depressão/diagnóstico , Feminino , Humanos , Masculino , Regiões Promotoras Genéticas/genética , Fatores de Risco , Fatores de Tempo
15.
Int J Geriatr Psychiatry ; 30(6): 631-8, 2015 Jun.
Artigo em Inglês | MEDLINE | ID: mdl-25187003

RESUMO

OBJECTIVE: We evaluated the short-term efficacy of a protocol of cognitive stimulation (CS), compared with a sham intervention, on cognitive performance in cognitively healthy individuals with a family history of dementia (NDFAM) and in non-demented individuals with cognitive impairment (CI). METHODS: We performed a randomized controlled trial of CS in NDFAM and CI. CS consisted in 10 twice weekly meetings of CS focused on a specific cognitive area. CS was compared with a sham intervention (CT) using Mini-mental state examination (MMSE), Montreal Cognitive Assessment (MoCA), and the Corsi test. All study participants were typed for the presence of apolipoprotein E (APOE)-Ɛ4. RESULTS: Cognitively healthy NDFAM showed a higher net cognitive gain after CS, as reflected in their MoCA score, and a borderline significant net increase in visuospatial memory (Corsi test) compared with those receiving the CT. APOE-Ɛ4 carriers showed a less significant improvement on the Corsi test with respect to APOE-Ɛ4 non-carriers. In the CI sample, the MoCA and Corsi test results did not differ between the cognitively stimulated subjects and the controls. No changes in MMSE scores were found in either sample of subjects. CONCLUSIONS: These findings suggest that CS as structured in this study is an effective treatment in cognitively healthy individuals, whereas it is less effective in individuals with CI. Moreover, evaluation of APOE-Ɛ4 status provided evidence of a substantial genetic contribution to the efficacy of CS on visuospatial memory as measured using the Corsi test.


Assuntos
Transtornos Cognitivos/terapia , Cognição/fisiologia , Terapia Cognitivo-Comportamental , Idoso , Idoso de 80 Anos ou mais , Apolipoproteína E4/genética , Transtornos Cognitivos/genética , Transtornos Cognitivos/fisiopatologia , Demência/genética , Feminino , Humanos , Masculino , Memória/fisiologia , Testes Neuropsicológicos
16.
Arch Gerontol Geriatr ; 60(2): 334-43, 2015.
Artigo em Inglês | MEDLINE | ID: mdl-25466513

RESUMO

The age-specific prevalence rates of dementia vary widely. Studies focusing on specific age groups are needed to provide reliable estimates for healthcare providers and policy makers. We estimated the prevalence of dementia, dementia subtypes and cognitive impairment in "InveCe.Ab" (ClinicalTrials.gov, NCT01345110), a single-step multidimensional population-based study of 70-74-year olds living in Abbiategrasso (Milan, Italy). We also looked for associations with socio-demographic factors and the presence of the apolipoprotein E-ɛ4 allele. The overall dementia prevalence was 3% (95%CI: 2.1-4.1%) [Alzheimer's disease (AD): 1.2% (95%CI 0.6-1.9%); vascular dementia (VD): 1.4% (95%CI: 0.8-2.2%)]. Being single was found to be a risk factor for vascular dementia; subjects born in southern Italy were shown to be at greater risk both of overall dementia and of vascular dementia. The prevalence of cognitive impairment, with or without subjective cognitive complaints (cognitive impairment, no dementia, CIND) was 7.8% (95%CI: 6.4-9.4%). As regards the CIND subgroups, the prevalence of subjects with subjective cognitive complaints (mild cognitive impairment, MCI) was 5.0% (95%CI 3.9-6.3%), while the prevalence of those without MCI (CIND-other) was 2.8% (95%CI: 1.9-3.8). The males had a higher risk of MCI and CIND-other; the older subjects were more likely to have MCI, and those born in north-eastern Italy to have CIND-other. The prevalence of AD was higher among the apolipoprotein E-ɛ4 carriers. Our data highlight the importance of dementia and cognitive impairment in the transitional period from adulthood to old age, and reveal the presence of different associations with socio-demographic and genetic factors.


Assuntos
Apolipoproteína E4/genética , Transtornos Cognitivos/epidemiologia , Transtornos Cognitivos/genética , Demência/epidemiologia , Demência/genética , Fatores Etários , Idoso , Escolaridade , Feminino , Heterozigoto , Humanos , Itália/epidemiologia , Masculino , Estado Civil , Prevalência , Estudos Prospectivos , Fatores de Risco , Fatores Sexuais
17.
BMC Geriatr ; 13: 98, 2013 Sep 24.
Artigo em Inglês | MEDLINE | ID: mdl-24063518

RESUMO

BACKGROUND: Developed countries are experiencing an unprecedented increase in life expectancy that is accompanied by a tremendous rise in the number of people with dementia. The purpose of this paper is to report on the study design and methodology of an Italian population-based study on brain aging and dementia in the elderly. This multi-domain study is structured in two phases. Our goal is to gather sufficient data to estimate the prevalence (phase I: cross-sectional study), the incidence and the progression of dementia and its subtypes as well as cognitive impairment (phase II: follow-up study) and to identify socio-demographic, clinical, and lifestyle factors associated with dementia and the quality of brain aging in people aged 70-74 years, a crucial point between late adulthood and old age. METHODS/DESIGN: We chose to contact all 1773 people born between 1935-39 residing in Abbiategrasso, Milan, Italy. Those who agreed to participate in the "Invece.Ab" study were enrolled in a cross-sectional assessment and will be contacted two and four years after the initial data collection to participate in the longitudinal survey. Both the cross-sectional and longitudinal assessments include a medical evaluation, a neuropsychological test battery, several anthropometric measurements, a social and lifestyle interview, blood analyses, and the storage of a blood sample for the evaluation of putative biological markers. DISCUSSION: Now at the end of the recruitment phase, the evaluable population has amounted to 1644 people. Among these, 1321 (80.35%) of the participants have completed phase I. This high return rate was likely due to the style of recruitment and personalization of the contacts.


Assuntos
Envelhecimento/patologia , Envelhecimento/psicologia , Encéfalo/patologia , Demência/diagnóstico , Demência/psicologia , Vigilância da População/métodos , Idoso , Estudos Transversais , Demência/epidemiologia , Feminino , Seguimentos , Humanos , Itália/epidemiologia , Estudos Longitudinais , Masculino , Projetos Piloto
18.
Am J Neurodegener Dis ; 2(1): 40-5, 2013.
Artigo em Inglês | MEDLINE | ID: mdl-23515357

RESUMO

One of the current challenge in Alzheimer's disease (AD) is the identification of reliable biomarkers that might improve diagnostic accuracy, possibly correlating with the disease progression and patient's response to therapy. As the clinically validated AD biomarkers evaluate cerebrospinal fluid (CSF) parameters, the need for less invasive diagnostic markers is well evident. To this respect, blood circulating cytokines or growth factors have provided some encouraging results, even though no clinically validated to date. In 2007 Ray et al suggested a panel of 18 circulating molecules that might increase AD diagnostic accuracy. In an attempt of replicating their data, we designed a multiplex fluorimetric assay comprising 16 independent analytes and covering 15 out of the 18 described proteins. We collected serum samples from three diagnostic groups: probable AD (n=33), matched healthy controls (CNT, n=23) and non AD demented (NAD, n=14). After correction for age, we found an increased level of EGF-1 in AD in comparison to CNT and NAD, while an increase of TRAIL-R4 was found in NAD. However, evaluation of specificity/sensitivity by ROC curve analysis gave weak evidence of diagnostic accuracy (area under the curve = 0.63 and 0.66 for EGF and TRAIL-R4, respectively). Finally, we tried to find a diagnostic classifier by a multivariate algorithm. We found indication of diagnostic evidence for AD only, while NAD samples did not show a diagnostic pattern.

19.
Alzheimers Dement ; 9(4): 392-9, 2013 Jul.
Artigo em Inglês | MEDLINE | ID: mdl-22651940

RESUMO

BACKGROUND: Human sirtuins are a current hotspot for research in neurodegenerative disorders, including Alzheimer's disease (AD). This study investigated whether genetic variants in two members of the sirtuin family, SIRT2 and SIRT3, affected AD susceptibility. METHODS: A genetic case-control study was performed, comprising 534 probable AD cases and 638 nondemented control subjects from the north of Italy and Canton Ticino, Switzerland (discovery population). The study was focused on SIRT2 rs10410544, SIRT3 rs4980329, and SIRT3 rs536715 single nucleotide polymorphisms (SNPs). These SNPs were genotyped by real-time polymerase chain reaction allelic discrimination assay or restriction fragment length polymorphism. The SNPs rs7412 and rs429358, mapping within the apolipoprotein E (APOE) gene, were genotyped by real-time polymerase chain reaction allelic discrimination assay too. In a replication population comprising 756 AD cases and 847 nondemented control subjects, SIRT2 rs10410544, APOE rs7412, and APOE rs429358 were genotyped as mentioned previously. RESULTS: In the discovery population, we observed an association between SIRT2 rs10410544 T allele and AD (adjusted odds ratio [OR] = 1.23, 95% confidence interval [CI]: 1.02-1.50, P = .02, after correction for sex, age, and APOE ε4 genotype). The association between AD and SIRT2 rs10410544 T allele was only present in APOE ε4 noncarriers (adjusted OR = 1.29, 95% CI: 1.03-1.61, P = .03). The replication study did not confirm this evidence. However, the combined analysis on the two cohorts detected the association (adjusted OR = 1.17, 95% CI: 1.02-1.35, P = .02), and only APOE ε4 noncarriers were at risk (adjusted OR = 1.2, 95% CI: 1.02-1.43, P = .03). CONCLUSIONS: The SIRT2 rs10410544 T allele deserves further investigation as a novel minor genetic risk factor for AD in the APOE ε4-negative Caucasian population.


Assuntos
Doença de Alzheimer/genética , Apolipoproteínas E/genética , Polimorfismo de Nucleotídeo Único , Sirtuína 2/genética , Idoso , Idoso de 80 Anos ou mais , Alelos , Doença de Alzheimer/epidemiologia , Apolipoproteína E4/genética , Estudos de Casos e Controles , Grupo com Ancestrais do Continente Europeu/genética , Feminino , Predisposição Genética para Doença , Genótipo , Humanos , Itália , Masculino , Pessoa de Meia-Idade , Polimorfismo de Fragmento de Restrição , Reação em Cadeia da Polimerase em Tempo Real , Reprodutibilidade dos Testes , Risco , Sirtuína 3/genética , Suíça
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