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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.
JAMA Netw Open ; 2(12): e1917126, 2019 Dec 02.
Artigo em Inglês | MEDLINE | ID: mdl-31825500

RESUMO

Importance: The amyloid/tau/neurodegeneration (A/T/N) framework uses cerebrospinal fluid (CSF) levels of total tau (tTau) as a marker of neurodegeneration and CSF levels of phosphorylated tau 181 (pTau181) as a marker of tau tangles. However, it is unclear whether CSF levels of tTau and pTau181 have similar or different trajectories over the course of Alzheimer disease. Objectives: To examine the rates of change in CSF levels of tTau and pTau181 across the Alzheimer disease course and how the rates of change are associated with brain atrophy as measured by magnetic resonance imaging. Design, Setting, and Participants: This cohort study was set in tertiary research clinics. Each participant was a member of a pedigree with a known mutation for dominantly inherited Alzheimer disease. Participants were divided into 3 groups on the basis of the presence of a mutation and their Clinical Dementia Rating score. Data analysis was performed in June 2019. Main Outcomes and Measures: Rates of change of CSF tTau and pTau181 levels and their association with the rate of change of brain volume. Results: Data from 465 participants (283 mutation carriers and 182 noncarriers) were analyzed. The mean (SD) age of the cohort was 37.8 (11.3) years, and 262 (56.3%) were women. The mean (SD) follow-up duration was 2.7 (1.5) years. Two or more longitudinal CSF and magnetic resonance imaging assessments were available for 160 and 247 participants, respectively. Sixty-five percent of mutation carriers (183) did not have symptoms at baseline (Clinical Dementia Rating score, 0). For mutation carriers, the annual rates of change for CSF tTau and pTau181 became significantly different from 0 approximately 10 years before the estimated year of onset (mean [SE] rates of change, 5.5 [2.8] for tTau [P = .05] and 0.7 [0.3] for pTau 181 [P = .04]) and 15 years before onset (mean [SE] rates of change, 5.4 [3.9] for tTau [P = .17] and 1.1 [0.5] for pTau181 [P = .03]), respectively. The rate of change of pTau181 was positive and increased at the early stages of the disease, showing a positive rate of change starting at 15 estimated years before onset until 5 estimated years before onset (mean [SE], 0.4 [0.3]), followed by a positive but decreasing rate of change at year 0 (mean [SE], 0.1 [0.3]) and then negative rates of change at 5 years (mean [SE], -0.3 [0.4]) and 10 years (mean [SE], -0.6 [0.6]) after symptom onset. In individuals without symptoms (Clinical Dementia Rating score, 0), the rates of change of CSF tTau and pTau181 were negatively associated with brain atrophy (high rates of change in CSF measures were associated with low rates of change in brain volume in asymptomatic stages). After symptom onset (Clinical Dementia Rating score, >0), an increased rate of brain atrophy was not associated with rates of change of levels of both CSF tTau and pTau181. Conclusions and Relevance: These findings suggest that CSF tTau and pTau181 may have different associations with brain atrophy across the disease time course. These results have implications for understanding the dynamics of disease pathobiology and interpreting neuronal injury biomarker concentrations in response to Alzheimer disease progression and disease-modifying therapies.

4.
Handb Clin Neurol ; 165: 33-45, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31727221

RESUMO

Recent research reveals an overlap between frontotemporal dementia (FTD) and a variety of primary psychiatric disorders, challenging the artificial divisions between psychiatry and neurology. This chapter offers an overview of the clinical syndromes associated with FTD while describing links between these syndromes and neuroimaging. This is followed by a review of the neuropathology and genetic changes in the brain. We will illustrate the syndromic overlap that exists between FTD and several primary psychiatric disorders including bipolar affective disorder and schizophrenia. Emphasis will be placed on the behavioral variant of FTD (bvFTD), which is the common clinical syndrome seen with degeneration of the frontal lobes and is the most likely to be encountered in psychiatric settings.

5.
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
6.
PLoS One ; 13(4): e0195133, 2018.
Artigo em Inglês | MEDLINE | ID: mdl-29649337

RESUMO

BACKGROUND: Adult leg length is influenced by nutrition in the first few years of life. Adult head circumference is an indicator of brain growth. Cross-sectional studies indicate inverse associations with dementia risk, but there have been few prospective studies. METHODS: Population-based cohort studies in urban sites in Cuba, Dominican Republic Puerto Rico and Venezuela, and rural and urban sites in Peru, Mexico and China. Sociodemographic and risk factor questionnaires were administered to all participants, and anthropometric measures taken, with ascertainment of incident dementia, and mortality, three to five years later. RESULTS: Of the original at risk cohort of 13,587 persons aged 65 years and over, 2,443 (18.0%) were lost to follow-up; 10,540 persons with skull circumference assessments were followed up for 40,466 person years, and 10,400 with leg length assessments were followed up for 39,954 person years. There were 1,009 cases of incident dementia, and 1,605 dementia free deaths. The fixed effect pooled meta-analysed adjusted subhazard ratio (ASHR) for leg length (highest vs. lowest quarter) was 0.80 (95% CI, 0.66-0.97) and for skull circumference was 1.02 (95% CI, 0.84-1.25), with no heterogeneity of effect between sites (I2 = 0%). Leg length measurements tended to be shorter at follow-up, particularly for those with baseline cognitive impairment and dementia. However, leg length change was not associated with dementia incidence (ASHR, per cm 1.006, 95% CI 0.992-1.020), and the effect of leg length was little altered after adjusting for baseline frailty (ASHR 0.82, 95% CI 0.67-0.99). A priori hypotheses regarding effect modification by gender or educational level were not supported. However, the effect of skull circumference was modified by gender (M vs F ASHR 0.86, 95% CI 0.75-0.98), but in the opposite direction to that hypothesized with a greater protective effect of larger skull dimensions in men. CONCLUSIONS: Consistent findings across settings provide quite strong support for an association between adult leg length and dementia incidence in late-life. Leg length is a relatively stable marker of early life nutritional programming, which may confer brain reserve and protect against neurodegeneration in later life through mitigation of cardiometabolic risk. Further clarification of these associations could inform predictive models for future dementia incidence in the context of secular trends in adult height, and invigorate global efforts to improve childhood nutrition, growth and development.


Assuntos
Demência/epidemiologia , Demência/fisiopatologia , Perna (Membro)/anatomia & histologia , Crânio/anatomia & histologia , Idoso , Idoso de 80 Anos ou mais , Antropometria , China/epidemiologia , Estudos de Coortes , Estudos Transversais , Características Culturais , Feminino , Seguimentos , Idoso Fragilizado , Humanos , Incidência , América Latina/epidemiologia , Masculino , Modelos de Riscos Proporcionais , Estudos Prospectivos , Análise de Regressão , Fatores de Risco , Classe Social , Inquéritos e Questionários
7.
MEDICC Rev ; 19(1): 31-35, 2017 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-28225543

RESUMO

Aging and Alzheimer is a prospective, longitudinal cohort study involving 2944 adults aged ≥65 years from selected areas in Cuba's Havana and Matanzas Provinces. This door-to-door study, which began in 2003, includes periodic assessments of the cohort based on an interview; physical exam; anthropometric measurements; and diagnosis of dementia and its subtypes, other mental disorders, and other chronic non-communicable diseases and their risk factors. Information was gathered on sociodemographic characteristics; disability, dependency and frailty; use of health services; and characteristics of care and caregiver burden. The first assessment also included blood tests: complete blood count, blood glucose, kidney and liver function, lipid profile and ApoE4 genotype (a susceptibility marker). In 2007-2011, the second assessment was done of 2010 study subjects aged ≥65 years who were still alive. The study provides data on prevalence and incidence of dementia and its risk factors, and of related conditions that affect the health of older adults. It also contributes valuable experiences from field work and interactions with older adults and their families. Building on lessons learned, a third assessment to be done in 2016-2018 will incorporate a community intervention strategy to respond to diseases and conditions that predispose to dementia, frailty and dependency in older adults. KEYWORDS Dementia, Alzheimer disease, chronic disease, aging, chronic illness, frailty, dependency, cohort studies, Cuba.


Assuntos
Doença de Alzheimer/epidemiologia , Idoso , Idoso de 80 Anos ou mais , Envelhecimento , Doença de Alzheimer/diagnóstico , Doença de Alzheimer/genética , Apolipoproteína E4/genética , Doença Crônica/epidemiologia , Cuba/epidemiologia , Demência/diagnóstico , Demência/epidemiologia , Feminino , Humanos , Incidência , Entrevistas como Assunto , Estudos Longitudinais , Masculino , Prevalência , Fatores de Risco , Inquéritos e Questionários
8.
Dement. neuropsychol ; 8(4)dez. 2014.
Artigo em Inglês | LILACS | ID: lil-737363

RESUMO

Objective: In an admixed population of older Cubans, the incidence and association of APOE and sociodemographic risk factors with dementia incidence was estimated. Methods: A single-phase survey (baseline) of all over 65-year-olds residing in seven catchment areas in Cuba (n=2944) was conducted between 2003 and 2007. Dementia diagnosis was established according to DSM-IV and 10/66 criteria. APOE genotype was determined in 2520 participants. An incidence wave was conducted 4.5 years after cohort inception in order to estimate incidence and associations with sociodemographic risk factors of the APOE ?4 genotype. Results: The incidence rate of DSM IV dementia was 9.0 per 1000 person-years (95% CI 7.2-11.3) and of 10/66 dementia was 20.5 per 1000 person-years (95% CI, 17.6-23.5). Older age, a family history of dementia and APOE e4 genotype were independent risk factors for incident 10/66 dementia. APOE genotype was associated cross-sectionally with dementiaprevalence, but the effect on the incidence of dementia was attenuated, and only apparent among those in the youngest age group. Conclusion: The incidence of dementia in the older Cuban population is relatively high and similar to levels reported in Europe and North-America. The study showed that the relationship between APOE e4 and incident dementia is stronger in the younger-old than the older-old and that this change must be taken into account in models of dementia.


Objetivo: Em uma população miscigenada de cubanos idosos, estimamos a incidência de demência e a associação entre o genótipo da APOE e os fatores de risco sociodemográficos na incidência de demência. Métodos: Realizamos uma pesquisa de uma fase (linha de base) de todos os idosos com mais de 65 anos residentes em sete áreas de Cuba (n=2944), de 2003 a 2007. O diagnóstico de demência foi estabelecido de acordo com os critérios do DSM-IV e do 10/66. O genótipo APOE foi determinado em 2520 participantes. Avaliação da incidência foi conduzida 4,5 anos após a linha de base, a fim de estimar a incidência e associações com fatores de risco sociodemográficos e o genótipo APOE 4. Resultados: A taxa de incidência de demência foi de 9,0 por 1000 pessoas-ano (IC 95% 7,2-11,3) de acordo com o DSM-IV e de 20,5 por 1000 pessoas-ano (IC95%, 17,6-23,5) de acordo com o 10/66. Idade avançada, história familiar de demência e genótipo APOE 4 foram fatores de risco independentes para a incidência de demência de acordo com os critérios do 10/66. O genótipo APOE foi associado com a prevalência de demência em estudo transversal, mas o efeito sobre a incidência de demência foi atenuado, e apenas aparente entre aqueles na faixa etária mais jovem. Conclusão: A incidência de demência na população cubana mais velha é relativamente alta, semelhante às relatadas na Europa e América do Norte. O estudo mostra que a relação entre APOE 4 incidente e demência é mais forte entre os idosos mais jovens e que esta alteração deve de ser considerada em modelos de demência.


Assuntos
Humanos , Apolipoproteínas E , Estudos Epidemiológicos , Fatores de Risco , Estudos de Coortes , Demência , América Latina
9.
MEDICC Rev ; 16(1): 24-30, 2014 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-24487672

RESUMO

INTRODUCTION: Population aging translates into more people with chronic non-communicable diseases, disability, frailty and dependency. The study of frailty--a clinical syndrome associated with an increased risk of falls, disability, hospitalization, institutionalization and death--is important to improve clinical practice and population health indicators. OBJECTIVES: In a cohort of older adults in Havana and Matanzas provinces, Cuba, estimate prevalence of frailty and its risk factors; determine incidence of dependency; estimate mortality risk and identify mortality predictors. METHODS: A prospective longitudinal study was conducted door to door, from June 2003 through July 2011, in a cohort of 2813 adults aged ≥65 years living in selected municipalities of Havana and Matanzas provinces; mean followup time was 4.1 years. Independent variables included demographics, behavioral risk factors and socioeconomic indicators, chronic non-communicable diseases (hypertension, stroke, dementia, depression, diabetes, anemia), number of comorbidities, and APOE ε4 genotype. Dependent variables were frailty, dependency and mortality. Criteria for frailty were slow walking speed, exhaustion, weight loss, low physical activity and cognitive decline. Prevalence and frailty risk were estimated by Poisson regression, while dependency and mortality risks and their predictors were determined using Cox regression. RESULTS: Frailty syndrome prevalence was 21.6% (CI 17.9%-23.8%) at baseline; it was positively associated with advanced age, anemia and presence of comorbidities (stroke, dementia, depression, three or more physically debilitating diseases). Male sex, higher educational level, married or partnered status, and more household amenities were inversely associated with frailty prevalence. In followup, dependency incidence was 33.1 per 1000 person-years (CI 29.1-37.6) and mortality was 55.1 per 1000 person-years. Advanced age, male sex, lower occupational status during productive years, dependency, frailty, dementia, depression, cerebrovascular disease and diabetes were all associated with higher risk of death. CONCLUSIONS: Given the challenge for developing countries presented by demographic and epidemiologic transition; the high prevalence in older adults of frailty syndrome, dependency and chronic non-communicable diseases; and the association of all these with higher mortality, attention should be targeted to older adults as a risk group. This should include greater social protection, age-appropriate health services, and modification and control of cardiovascular risk factors.


Assuntos
Idoso Fragilizado/estatística & dados numéricos , Vida Independente , Mortalidade/tendências , Idoso , Idoso de 80 Anos ou mais , Intervalos de Confiança , Cuba/epidemiologia , Feminino , Previsões , Humanos , Vida Independente/estatística & dados numéricos , Masculino , Estudos Prospectivos , Fatores de Risco
10.
Dement Neuropsychol ; 8(4): 356-363, 2014.
Artigo em Inglês | MEDLINE | ID: mdl-29213926

RESUMO

Objective: In an admixed population of older Cubans, the incidence and association of APOE and sociodemographic risk factors with dementia incidence was estimated. Methods: A single-phase survey (baseline) of all over 65-year-olds residing in seven catchment areas in Cuba (n=2944) was conducted between 2003 and 2007. Dementia diagnosis was established according to DSM-IV and 10/66 criteria. APOE genotype was determined in 2520 participants. An incidence wave was conducted 4.5 years after cohort inception in order to estimate incidence and associations with sociodemographic risk factors of the APOE ε4 genotype. Results: The incidence rate of DSM IV dementia was 9.0 per 1000 person-years (95% CI 7.2-11.3) and of 10/66 dementia was 20.5 per 1000 person-years (95% CI, 17.6-23.5). Older age, a family history of dementia and APOE ε4 genotype were independent risk factors for incident 10/66 dementia. APOE genotype was associated cross-sectionally with dementia prevalence, but the effect on the incidence of dementia was attenuated, and only apparent among those in the youngest age group. Conclusion: The incidence of dementia in the older Cuban population is relatively high and similar to levels reported in Europe and North-America. The study showed that the relationship between APOE ε4 and incident dementia is stronger in the younger-old than the older-old and that this change must be taken into account in models of dementia.

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