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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.

2.
Sci Rep ; 10(1): 7090, 2020 Apr 27.
Artigo em Inglês | MEDLINE | ID: mdl-32341386

RESUMO

To investigate (1) the effects of indoor incense burning upon cognition over 3 years; (2) the associations between indoor incense burning with the brain's structure and functional connectivity of the default mode network (DMN); and (3) the interactions between indoor incense burning and vascular disease markers upon cognitive functions. Community older adults without stroke or dementia were recruited (n = 515). Indoor incense use was self-reported as having burnt incense at home ≥ weekly basis over the past 5 years. Detailed neuropsychological battery was administered at baseline (n = 227) and the Montreal Cognitive Assessment at baseline and year 3 (n = 515). MRI structural measures and functional connectivity of the DMN were recorded at baseline. Demographic and vascular risk factors and levels of outdoor pollutants were treated as covariates. Indoor incense burning was associated with reduced performance across multiple cognitive domains at baseline and year 3 as well as decreased connectivity in the DMN. It interacted with diabetes mellitus, hyperlipidemia and white matter hyperintensities to predict poorer cognitive performance. Indoor incense burning is (1) associated with poorer cognitive performance over 3 years; (2) related to decreased brain connectivity; and (3) it interacts with vascular disease to predispose poor cognitive performance.

3.
Artigo em Inglês | MEDLINE | ID: mdl-32043518

RESUMO

BACKGROUND: Longitudinal evidence of poor visual acuity associating with higher risk of incident dementia is mixed. This study aimed to examine if poor visual acuity was associated with higher dementia incidence in a large community cohort of older adults, independent of the possible biases relating to misclassification error, reverse causality, and confounding effects due to health problems and behaviours. METHODS: A total of 15,576 community-living older adults without dementia at baseline were followed for 6 years to the outcome of incident dementia, which was diagnosed according to the ICD-10 or a Clinical Dementia Rating of 1 to 3. Visual acuity was assessed using the Snellen's chart at baseline and follow-up. Important variables including demographics (age, sex, education, and socioeconomic status), physical and psychiatric comorbidities (cardiovascular risks, ophthalmological conditions, hearing impairment, poor mobility, and depression), and lifestyle behaviours (smoking, diet, physical, intellectual, and social activities) were also assessed. RESULTS: Over 68,904 person-years of follow-up, 1,349 participants developed dementia. Poorer visual acuity at baseline was associated with higher dementia incidence in 6 years, even after adjusting for demographics, health problems, and lifestyle behaviours, and excluding those who developed dementia within 3 years after baseline. Compared with normal vision, the hazard ratio of dementia was 1.19 (p=0.31), 2.09 (p<0.001), and 8.66 (p<0.001) for mild, moderate, and severe visual impairment, respectively. CONCLUSIONS: Moderate-to-severe visual impairment could be a potential predictor and possibly a risk factor for dementia. From a clinical perspective, older adults with poor visual acuity might warrant further risk assessment for dementia.

4.
J Gerontol B Psychol Sci Soc Sci ; 75(3): 560-570, 2020 Feb 14.
Artigo em Inglês | MEDLINE | ID: mdl-30496547

RESUMO

OBJECTIVES: Dementia interferes with older adults' functioning in cognitive, daily, psychosocial, and neuroendocrine domains. The present study examined the psychophysiological effects of dance movement therapy (DMT) and physical exercise for older adults with dementia. METHODS: This randomized controlled trial recruited 204 older adults diagnosed with mild dementia into the DMT, exercise, or waitlist control group. Both DMT and exercise interventions had similar intensity and comprised 24 hr of intervention that spanned over 12 weeks. All participants completed self-report questionnaires on psychosocial well-being, daily functioning, neurocognitive assessments, and salivary cortisol measures at baseline and 3 follow-up measurements more than 1 year. RESULTS: The DMT group showed significant decreases in depression, loneliness, and negative mood (d = 0.33-0.42, p < .05) and improved daily functioning (d = 0.40, p < .01) and diurnal cortisol slope (d = 0.30, p < .01). The effects on daily functioning and cortisol slope remained at 1-year follow-up. The exercise group of matched intensity showed no significant effects on the outcomes. DISCUSSION: The study findings support the potential utility of DMT as a multifaceted intervention for improving various aspects of functioning in older adults with declining cognitive abilities. The lack of beneficial effects for our exercise intervention and long-term DMT effects highlights the need to maintain persistent levels of exercise with adequate intensity and duration.

5.
Int J Geriatr Psychiatry ; 35(2): 163-173, 2020 02.
Artigo em Inglês | MEDLINE | ID: mdl-31657091

RESUMO

OBJECTIVE: The aim of the present study was to characterize the clinical pathways that people with dementia (PwD) in different countries follow to reach specialized dementia care. METHODS: We recruited 548 consecutive clinical attendees with a standardized diagnosis of dementia, in 19 specialized public centres for dementia care in 15 countries. The WHO "encounter form," a standardized schedule that enables data concerning basic socio-demographic, clinical, and pathways data to be gathered, was completed for each participant. RESULTS: The median time from the appearance of the first symptoms to the first contact with specialist dementia care was 56 weeks. The primary point of access to care was the general practitioners (55.8%). Psychiatrists, geriatricians, and neurologists represented the most important second point of access. In about a third of cases, PwD were prescribed psychotropic drugs (mostly antidepressants and tranquillizers). Psychosocial interventions (such as psychological counselling, psychotherapy, and practical advice) were delivered in less than 3% of situations. The analyses of the "pathways diagram" revealed that the path of PwD to receiving care is complex and diverse across countries and that there are important barriers to clinical care. CONCLUSIONS: The study of pathways followed by PwD to reach specialized care has implications for the subsequent course and the outcome of dementia. Insights into local differences in the clinical presentations and the implementation of currently available dementia care are essential to develop more tailored strategies for these patients, locally, nationally, and internationally.

6.
J Atten Disord ; 24(1): 126-135, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30259782

RESUMO

Objective: We examined adulthood diagnostic, functioning, and social outcomes of childhood ADHD in a Hong Kong Chinese clinical sample. Method: We identified from the central registry 499 Chinese adults clinically diagnosed with ADHD aged 6 to 12 in 2002-2005 in four Hong Kong child psychiatric centers. Assessments included ADHD Clinical Diagnostic Scale (ACDS), Structured Clinical Interview for DSM Disorders (SCID), and World Health Organization Disability Assessment Schedule (WHO-DAS). Results: Eligible participants = 499. One hundred forty-five completed assessments, two deceased, six incarcerated, 100 had invalid contact, 83 declined, 34 emigrated, and 129 unable to attend. Mean follow-up duration = 14.9 years. Nonrespondents were slightly younger (19.78 vs. 20.53, p < .001). In all, 83.1% of all participants currently met Diagnostic and Statistical Manual of Mental Disorders (5th ed.; DSM-5) ADHD criteria (36.8% inattentive subtype (IA), 43% combined, 3.3% hyperactive/impulsive subtype (H/I) ). One third of persistent ADHD participants currently received care. ADHD persistence was associated with significantly increased psychiatric comorbidity (49.5% vs. 22.7%, p = .02) and poor academic and social outcomes. ADHD persistence and comorbidity independently predicted impairment. Conclusion: Adulthood-persistence of clinically presented childhood ADHD is common and impairing in Hong Kong Chinese.

7.
Aging Ment Health ; 24(1): 186-192, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-30270640

RESUMO

Objectives: Hong Kong - Vigilance and Memory Test (HK-VMT) is developed to distinguish early cognitive impairment in the pre-symptomatic phase from normal cognitive ageing in older adults. The objectives were to validate HK-VMT to differentiate mild cognitive impairment (MCI) and healthy control (HC), and to explore the cut-off scores for different educational levels.Method: A total of 606 older adults underwent the HK-VMT and conventional cognitive tests. HK-VMT is a 15 minutes cognitive battery that assesses episodic memory, attention, and visuospatial ability. The HK-VMT total is the sum of accuracy of all subtests with a range of 0 to 40. Differences in socio-demographic and clinical characteristics between groups were explored. Receiver operating characteristic (ROC) analyses were used to compare HK-VMT and Cantonese Mini Mental State Examination (CMMSE). A sample of 50 participants repeated the HK-VMT in 1 month to evaluate test-retest reliability.Results: ROC analysis of Area Under Curve (AUC) demonstrated that HK-VMT (AUC 0.793) was comparable to CMMSE (AUC 0.748) in differentiating MCI from HC in a matched sample. A cutoff at 21/22 was chosen yielding a sensitivity of 86.1% and a specificity of 75.3% for differentiating MCI and HC. Test-retest reliability of HK-VMT total was 0.71 (p<.001) in a month time.Conclusion: HK-VMT has demonstrated satisfactory validity in detecting cognitive impairment with good test-retest reliability in local older adults. It also performed favourably in the highly educated group when compared to CMMSE.

8.
Clin Nutr ; 2019 Nov 20.
Artigo em Inglês | MEDLINE | ID: mdl-31787369

RESUMO

BACKGROUND & AIMS: Mild cognitive impairment (MCI) patients are at risk of cognitive decline, while elevated serum homocysteine is also associated with cognitive impairment. Thus, older people with MCI and hyperhomocysteinemia may be under greater risk of cognitive decline. We therefore performed a randomized trial of homocysteine-lowering by B vitamins supplementation to prevent cognitive decline in older MCI patients with elevated serum homocysteine. METHODS: 279 MCI outpatients aged ≥65 years with serum homocysteine ≥10.0 µmol/L were randomly assigned to take either methylcobalamin 500 µg and folic acid 400 µg once daily, or two placebo tablets for 24 months. All subjects were followed up at 12 monthly intervals. The primary outcome was cognitive decline as defined by an increase in clinical dementia rating scale (CDR) sum of boxes (CDR_SOB). The secondary outcomes were global CDR, memory Z score, executive function Z score and Hamilton depression rating scale (HDRS) score. RESULTS: The clinical characteristics between two groups were well matched, except that the supplement group had better executive function. The supplement effectively lowered serum homocysteine (mean 13.9 ± sd 3.5 µmol at baseline to 9.3 ± 2.4 µmol/L at month 24). At month 24, there was no significant group difference in CDR_SOB or any secondary outcomes (mean changes in CDR_SOB 0.36 versus 0.22 in supplement and placebo groups respectively). At month 12, the supplement group significantly improved in executive function and had lower HDRS score (P = 0.004 and 0.012 respectively). Group difference was significant for HDRS, but borderline significant for executive function. (P = 0.01; 0.06 respectively) These effects were not significant at month 24. Subgroup analysis showed that aspirin use had significant interaction with B supplements in CDR_SOB at month 24 (Beta 0.189, P = 0.005). CONCLUSIONS: Vitamin B12 and folic acid supplementation did not reduce cognitive decline in older people with MCI and elevated serum homocysteine, though the cognitive decline over two years in placebo group was small. The supplement led to a significant reduction in depressive symptoms at month 12, though this effect was not sustained. Aspirin use had a negative interaction effect on cognitive functioning with B supplements. CLINICAL TRIAL REGISTRATION: Centre for Clinical Research and Biostatistics (CCRB) Clinical Trials Registry: CUHK_CCT00373.

9.
CNS Neurosci Ther ; 25(11): 1219-1221, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31696643
10.
Age Ageing ; 48(6): 838-844, 2019 11 01.
Artigo em Inglês | MEDLINE | ID: mdl-31574142

RESUMO

BACKGROUND: although type 2 diabetes increases risk of dementia by 2-fold, whether optimizing glycemic level in late life can reduce risk of dementia remains uncertain. We examined if achieving the glycemic goal recommended by the American Diabetes Association (ADA) within a year was associated with lower risk of dementia in 6 years. METHODS: in this population-based observational study, we examined 2246 community-living dementia-free Chinese older adults with type 2 diabetes who attended the Elderly Health Centres in Hong Kong at baseline and followed their HbA1c level and cognitive status for 6 years. In line with the ADA recommendation, we defined the glycemic goal as HbA1c < 7.5%. The study outcome was incident dementia in 6 years, diagnosed according to the 10th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD-10) or Clinical Dementia Rating of 1-3. RESULTS: those with HbA1c ≥ 7.5% at baseline and HbA1c < 7.5% in 1 year were associated with higher rather than lower incidence of dementia, independent of severe hypoglycemia, glycemic variability and other health factors. Sensitivity analyses showed that a relative reduction of ≥10%, but not 5-10%, in HbA1c within a year was associated with higher incidence of dementia in those with high (≥8%) and moderate (6.5-7.9%) HbA1c at baseline. CONCLUSION: a large reduction in HbA1c could be a potential predictor and possibly a risk factor for dementia in older adults with type 2 diabetes. Our findings suggest that optimizing or intensifying glycemic control in this population requires caution.

11.
Artigo em Inglês | MEDLINE | ID: mdl-31556447

RESUMO

OBJECTIVES: To examine the longer-term effects of benefit-finding on caregivers' depressive symptoms (primary outcome), and global burden, role overload, psychological well-being, and positive aspects of caregiving (secondary outcomes). METHOD: 96 Hong Kong Chinese caregivers of relatives with Alzheimer's disease were randomly assigned to receive the benefit-finding intervention (BFT) or one of two control conditions, namely, simplified psychoeducation (lectures only; SIM-PE) or standard psychoeducation (STD-PE). Caregivers received four biweekly one-to-one interventions of three hours each at their own homes. We focused on outcomes measured at 4- and 10-month follow-ups. The trajectories of intervention effects were modeled by BFT x time and BFT x time2 interaction terms. RESULTS: Mixed-effects regression showed significant BFT x time2 interaction effects on depressive symptoms against both control conditions, suggesting diminishing BFT effects over time. Z tests showed that, compared with controls, BFT participants reported substantial reductions in depressive symptoms at 4-month follow-up (d=-0.85 and -0.75 vs. SIM-PE and STD-PE respectively). For depressive symptoms measured at 10-month follow-up, BFT was indistinguishable from STD-PE whereas a moderate effect was observed in the comparison with SIM-PE (d=-0.52). Moreover, positive aspects of caregiving, but not other secondary outcomes, continued to show intervention effect up to 10-month follow-up. DISCUSSION: Benefit-finding is an efficacious intervention for depressive symptoms in Alzheimer caregivers, with strong effects in the medium-term post-intervention and possible moderate effects in the longer-term.

12.
CNS Neurosci Ther ; 25(11): 1270-1276, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31420949

RESUMO

BACKGROUND: Non-invasive brain stimulation (NIBS) is increasingly used as a probe of function and therapeutics in experimental neuroscience and neurorehabilitation. Scalp-to-cortex distance (SCD), as a key parameter, has been shown to potentially impact on the electric field. This study aimed to examine the region-specific SCD and its relationship with cognitive function in the context of age-related brain atrophy. METHODS: We analyzed the SCD and cortical thickness (CT) of left primary motor cortex (M1) in 164 cognitively normal (CN) adults and 43 dementia patients drawn from the Open Access Series of Imaging Studies (OASIS). The degree of brain atrophy was measured by the volume of ventricular system. Computational head model was developed to simulate the impact of SCD on the electric field. RESULTS: Increased SCD of left M1 was only found in dementia patients (P < .001). When considering CT, the ratio of SCD to CT (F = 27.41, P < .001) showed better differential value than SCD. The SCD of left M1 was associated with worse global cognition (r = -.207, P = .011) and enlarged third ventricle (r = .241, P < .001). The electric field was consequently reduced with the increased SCD across cognitively normal elderly and dementia groups. CONCLUSIONS: Scalable distance measures, including SCD and CT, are markedly correlated with reduced electric field in dementia patients. The findings suggest that it is important to be aware of region-specific distance measures when conducting NIBS-based rehabilitation in individuals with brain atrophy.

13.
J Trauma Stress ; 32(5): 664-676, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-31393657

RESUMO

This study examined the epidemiology of trauma exposure (TE) and posttraumatic stress disorder (PTSD) among community-dwelling Chinese adults in Hong Kong. Multistage stratification sampling design was used, and 5,377 participants were included. In Phase 1, TE, probable PTSD (p-PTSD), and psychiatric comorbid conditions were examined. In Phase 2, the Structured Clinical Interview for the DSM-IV (SCID-I) was used to determine the weighted diagnostic prevalence of lifetime full PTSD. Disability level and health service utilization were studied. The findings showed that the weighted prevalence of TE was 64.8%, and increased to 88.7% when indirect TE types were included, with transportation accidents (50.8%) reported as the most common TE. The prevalence of current p-PTSD among participants with TE was 2.9%. Results of logistic regression suggested that nine specific trauma types were significantly associated with p-PTSD; among this group, severe human suffering, sexual assault, unwanted or uncomfortable sexual experience, captivity, and sudden and violent death carried the greatest risks for developing PTSD, odds ratio (OR) = 2.32-2.69. The occurrence of p-PTSD was associated with more mental health burdens, including (a) sixfold higher rates for any past-week common mental disorder, OR = 28.4, (b) more mental health service utilization, p < .001, (c) poorer mental health indexes in level of symptomatology, suicide ideation and functioning, p < .001, and (d) more disability, ps < .001-p = .014. The associations found among TE, PTSD, and health service utilization suggest that both TE and PTSD should be considered public health concerns.

14.
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
15.
J Speech Lang Hear Res ; 62(7): 2411-2424, 2019 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-31251679

RESUMO

Purpose We report a preliminary study that prospectively tests the potential cognitive enhancing effect of foreign language (FL) learning in older adults with no clear signs of cognitive decline beyond what is age typical. Because language learning engages a large brain network that overlaps with the network of cognitive aging, we hypothesized that learning a new language later in life would be beneficial. Method Older adults were randomly assigned to 3 training groups: FL, games, and music appreciation. All were trained predominately by a computer-based program for 6 months, and their cognitive abilities were tested before, immediately after, and 3 months after training. Results FL and games, but not music appreciation, improved overall cognitive abilities that were maintained at 3 months after training. Conclusion This is the 1st randomized control study providing preliminary support for the cognitive benefits of FL learning.

16.
Am J Geriatr Psychiatry ; 27(9): 984-994, 2019 09.
Artigo em Inglês | MEDLINE | ID: mdl-31076215

RESUMO

OBJECTIVES: To examine the effects of the group benefit-finding therapeutic intervention (BFT) for Alzheimer family caregivers up to 10-month follow-up. METHODS: This was a cluster-randomized double-blind controlled trial in social centers and clinics. Participants included 129 caregivers. Inclusion criteria were 1) primary caregiver aged 18 years and older and without cognitive impairment, 2) providing 14 or more care hours per week to a relative with mild-to-moderate Alzheimer disease, and 3) scoring 3 or more on the Hamilton Depression Rating Scale. Exclusion criterion was care-recipient having parkinsonism or other forms of dementia. BFT (using cognitive reappraisal to find positive meanings) was evaluated against two forms of psychoeducation as controls-standard and simplified (lectures only) psychoeducation. All interventions had eight weekly sessions of 2 hours each. Primary outcome was depressive symptoms, whereas secondary outcomes were global burden, role overload, and psychological well-being. Measures were collected at baseline, postintervention, and 4- and 10-month follow-up. RESULTS: Mixed-effects regression showed that BFT's effect on depressive symptoms conformed to a curvilinear pattern, in which the strong initial effect leveled out after postintervention and was maintained up to 10-month follow-up; this was true when compared against either control group. The effect on global burden was less impressive but moderate effect sizes were found at the two follow-ups. For psychological well-being, there was an increase in the BFT group at 4-month follow-up and a return to baseline afterward. No effect on role overload was found. CONCLUSION: Benefit-finding reduces depressive symptoms as well as global burden in the long-term and increases psychological well-being in the medium-term.

17.
Am J Alzheimers Dis Other Demen ; 34(5): 302-307, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31064198

RESUMO

Alzheimer's disease (AD) is the most prevalent form of dementia, and age is strongly associated with the incidence of AD. This study aimed to investigate the association between the genotypes of CYP2D6, CYP3A4, and CYP2C9 genes to the clinical efficacy and tolerability of cholinesterase inhibitors (ChEIs) in Chinese patients with AD. One hundred seventy-nine patients with AD with newly prescribed with ChEIs were recruited. The clinical response and tolerability were evaluated at baseline, 3rd-, 6th-, and 12th-month follow-ups and were compared according to their genotypes of CYP2D6, CYP3A4, and CYP2C9. Among patients prescribed with donepezil/galantamine, CYP2D6*10 carriers showed significantly less side effects (P = .009). CYP2D6*10 carriers responded better to ChEIs and resulted in better improvement in Alzheimer's Disease Assessment Scale-Cognitive subscale (P = .027) and Mini-Mental State Examination (P = .012). Further study is required to replicate the finding, and it might be useful for clinicians to decide the medication based on the patients' CYP genotypes.

18.
Int Psychogeriatr ; 31(8): 1099-1107, 2019 08.
Artigo em Inglês | MEDLINE | ID: mdl-31030690

RESUMO

OBJECTIVE: The study of predeath grief is hampered by measures that are often lengthy and not clearly differentiated from other caregiving outcomes, most notably burden. We aimed to validate a new 11-item Caregiver Grief Questionnaire (CGQ) assessing two dimensions of predeath grief, namely relational deprivation and emotional pain. DESIGN: Cross-sectional survey. SETTING: Community and psychogeriatric clinics. PARTICIPANTS: 173 Alzheimer (AD) caregivers who cared for relatives with different degrees of severity (63 mild, 60 moderate, and 50 severe). MEASUREMENTS: Besides the CGQ, measures of caregiver burden and depressive symptoms, and care-recipients' neuropsychiatric symptoms and functional impairment were assessed. RESULTS: Confirmatory factor analysis supported the hypothesized 2-factor over the 1-factor model, and both subscales were only moderately correlated with burden. Two-week test-retest reliabilities were excellent. Caregivers for mild AD reported less grief than those caring for more severe relatives. Z tests revealed significantly different correlational patterns for the two dimensions, with emotional pain more related to global burden and depressive symptoms, and relational deprivation more related to care-recipients' functional impairment. Both dimensions were mildly correlated with neuropsychiatric symptoms (especially disruptive behaviors and psychotic symptoms) of the care-recipient. CONCLUSIONS: Results supported the reliability and validity of the two-dimensional measure of predeath grief. As a brief measure, it can be readily added to research instruments to facilitate study of this important phenomenon along with other caregiving outcomes.

19.
Cancer ; 125(15): 2561-2569, 2019 Aug 01.
Artigo em Inglês | MEDLINE | ID: mdl-31012963

RESUMO

BACKGROUND: Prostate cancer is radiosensitive. Prostate-specific membrane antigen (PSMA) is selectively overexpressed on advanced, castration-resistant tumors. Lutetium-177-labeled anti-PSMA monoclonal antibody J591 (177 Lu-J591) targets prostate cancer with efficacy and dose-response/toxicity data when delivered as a single dose. Dose fractionation may allow higher doses to be administered safely. METHOD: Men with metastatic castration-resistant prostate cancer refractory to or refusing standard treatment options with normal neutrophil and platelet counts were enrolled in initial phase 1b dose-escalation cohorts followed by phase 2a cohorts treated at recommended phase 2 doses (RP2Ds) comprising 2 fractionated doses of 177 Lu-J591 2 weeks apart. 177 Lu-J591 imaging was performed after treatment, but no selection for PSMA expression was performed before enrollment. Phase 2 patients had circulating tumor cell (CTC) counts assessed before and after treatment. RESULTS: Forty-nine men received fractionated doses of 177 Lu-J591 ranging from 20 to 45 mCi/m2 ×2 two weeks apart. The dose-limiting toxicity in phase 1 was neutropenia. The RP2Ds were 40 mCi/m2 and 45 mCi/m2 ×2. At the highest RP2D (45 mCi/m2 ×2), 35.3% of patients had reversible grade 4 neutropenia, and 58.8% of patients had thrombocytopenia. This dose showed a greater decrease in prostate-specific antigen (PSA) levels and longer survival (87.5% with any PSA decrease, 58.8% with >30% decrease, 29.4% with >50% decrease; median survival, 42.3 months [95% confidence interval, 19.9-64.7]). Fourteen of 17 (82%) patients with detectable CTCs experienced a decrease in CTC count. Overall, 79.6% of patients had positive PSMA imaging; those with less intense PSMA imaging tended to have poorer responses. CONCLUSION: Fractionated administration of 177 Lu-J591 allowed higher cumulative radiation dosing. The frequency and depth of PSA decrease, overall survival, and toxicity (dose-limiting myelosuppression) increased with higher doses.

20.
J Gastroenterol Hepatol ; 34(10): 1736-1742, 2019 Oct.
Artigo em Inglês | MEDLINE | ID: mdl-30891824

RESUMO

BACKGROUND AND AIM: Comorbid generalized anxiety disorder and irritable bowel syndrome are common and therapeutically challenging. We aimed to assess the effectiveness of electroacupuncture in relieving anxiety and bowel symptoms in Chinese adults with this form of comorbidity. METHODS: In a single-blind randomized sham-controlled trial, subjects with comorbid generalized anxiety disorder and irritable bowel syndrome were randomly assigned to receive 10 weekly sessions of electroacupuncture or sham electroacupuncture. Patients were assessed at baseline, immediately after intervention and at 6-week follow-up. Primary outcome was anxiety (7-item Patient Health Questionnaire section for anxiety). Secondary outcomes included bowel symptoms (bowel symptoms questionnaire), depressive symptoms (9-item Patient Health Questionnaire), somatic symptoms (15-item Patient Health Questionnaire), and health-related quality of life (EuroQol-5 Dimensions). RESULTS: Eighty subjects, 40 in each arm, were randomized. All but two in the sham group completed 10 weekly sessions. There was no significant difference in the proportion of patients experiencing significant (≥ 50%) reduction of anxiety symptoms between the two groups immediately after intervention (32.4% vs 21.6%, P = 0.06) and at 6-week follow-up (25.7% in electroacupuncture vs 27% in sham, P = 0.65). Anxiety, depressive symptom, and bowel symptom severity did not differ significantly between electroacupuncture and sham groups. CONCLUSIONS: Findings failed to support the effectiveness of electroacupuncture for comorbid generalized anxiety disorder and irritable bowel syndrome. Further studies are needed to identify effective acupuncture treatment protocols for such comorbidity.

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