Journal of Geriatric Psychiatry and Neurology最新文献

BackgroundEndoplasmic reticulum (ER) stress-induced neurodegeneration has been considered an underlying cause of Alzheimer disease (AD). Here, we investigated the beneficial effects of licochalcone A (Lico A), a valuable flavonoid of the root of the Glycyrrhiza species, against cognitive impairment in AD by regulating ER stress.MethodsThe triple transgenic mouse AD models were used and were administrated 5 or 15 mg/kg Lico A. Cognitive deficits, Aβ deposition, ER stress, and neuronal apoptosis were determined using Morris Water Maze test, probe trial, immunofluorescence staining, western blotting, and TUNEL staining. To investigate the mechanisms of how Lico A exerts anti-AD effects, primary hippocampal neurons were isolated from the AD model mice and treated with Lico A, salubrinal, an eIF2α phosphatase inhibitor, ML385, a Nrf2 inhibitor, or LY294002, an inhibitor of PI3K. Pharmacokinetics and toxicity of Lico A (15 mg/kg) in AD mice were evaluated.ResultsWe found that Lico A improved cognitive impairment, decreased Aβ plaques, inhibited ER stress, and reduced neuronal apoptosis in the hippocampus and cortex of AD mice. Treatment with Lico A in primary hippocampal neurons exerted the same effects as it did in vivo. Additionally, cotreatment with ML385 or LY294002 significantly impeded the effects of Lico A against ER stress. Moreover, 15 mg/kg Lico A had a good bioavailability and low toxicity in AD mice.ConclusionOur results demonstrated that Lico A ameliorates ER stress-induced neuronal apoptosis by inhibiting PERK/eIF2α/ATF4/CHOP signaling, suggesting the therapeutic potential of Lico A in AD treatment.

BackgroundThis is a new algorithm from the Psychopharmacology Algorithm Project at the Harvard South Shore Program, focused on generalized anxiety disorder (GAD) in older adults. Pertinent articles were identified and reviewed.ResultsSelective serotonin reuptake inhibitors (SSRIs) are considered to be first-line medications, with a preference for sertraline or escitalopram. If avoiding sexual side effects is a priority, buspirone is an option for the relatively healthy older adult. If response is inadequate, the second recommended trial is with a different SSRI or one of the serotonin-norepinephrine update inhibitors (SNRIs), venlafaxine or duloxetine. For a third medication trial, additional alternatives added to the previous options now include pregabalin/gabapentin, lavender oil, and agomelatine. If there is an unsatisfactory response to the third option chosen, quetiapine may be considered. We recommend caution with the following for acute treatment in this population: benzodiazepines and hydroxyzine. Other agents given low priority but having some supportive evidence were vilazodone, vortioxetine, mirtazapine, and cannabidiol. Acknowledging that the median age of onset of GAD is in early adulthood, many patients with GAD will have been started on benzodiazepines (or other medications that require caution in the elderly) for GAD at a younger age. These medications may be continued with regular observation to see if the potential harms are starting to exceed the benefits and a switch to other recommended agents may be justified.

ObjectivesRates of post-traumatic stress disorder (PTSD) among older adults range from 0.4%-4.5%. Research examining PTSD in adults has demonstrated numerous associations between physical and mental health conditions; however, these are less well characterized in older adults. The current study aimed to identify base rates of such conditions among older adults with and without a history of PTSD.MethodIn a case control design using the National Alzheimer's Coordinating Center Uniform Data Set, adults 65 years or older from the United States who endorsed either the presence or absence of PTSD were matched by age to assess between-group differences (N = 472; 236 pairs). We examined differences across self-reported sociodemographics and physical health, mental health, and substance use histories.ResultsMore participants with a history of PTSD identified as Hispanic, non-white, non-married, and functionally independent. Compared to individuals without a history of PTSD, significantly more individuals with a history of PTSD had histories of depression, anxiety, substance abuse, Parkinson's disease, seizures, insomnia, and TBI. Among participants without PTSD history, only 14.7% reported a history of TBI, compared to 41.1% of individuals with PTSD history.ConclusionsFindings showed expected trends toward worse physical and mental health among older adults with self-reported PTSD. There was a striking difference in the frequency of TBI history between participants with and without PTSD. These findings underscore a need to assess for PTSD among older adults, particularly those reporting a history of TBI.

Background and ObjectivesHearing aids may reduce the risk of dementia among individuals with hearing loss. However, no evidence is available from randomized controlled trials (RCTs) on the effectiveness of hearing aids use in reducing incident dementia. Using target trial emulation, we leveraged an existing longitudinal cohort study to estimate the association between hearing aids initiation and risk of dementia.Research Design and MethodsThe Health and Retirement Study was used to emulate target trials among non-institutionalized participants aged ≥50 years with self-reported hearing loss, without dementia at baseline, and without use of hearing aids in the previous 2 years. Intention-to-treat analysis was conducted to estimate the risk of dementia associated with hearing aids initiation vs controls who did not initiate hearing aids. Pooled logistic regression models with inverse-probability of treatment and censoring weights were applied to estimate risk ratios, and 95% confidence intervals were calculated using 1000 sets of bootstrapping.ResultsAmong 2314 participants (328 in the intervention group and 1986 in the control group; average age: 72.3 ± 9.7 years, 49% women, and 81% White), after 8 years of follow-up, risk of dementia was significantly lower among individuals who initiated hearing aids (risk difference (RD): -0.05, 95% confidence interval (CI): -0.08, -0.01). A lower risk was observed particularly among adults aged 50-74 years, men, and individuals with cardiovascular disease.Discussion and ImplicationsHearing aids use was associated with a significant reduction of incident dementia. Future interventional studies are needed to further assess the effectiveness of hearing aids in preventing dementia.

ObjectiveThe study aimed to evaluate the impact of Botulinum toxin A (BoNT/A) on neuropsychiatric symptoms in Parkinson's disease (PD) patients.MethodsA total of 125 PD patients and an equal number of age- and gender-matched healthy controls were involved. Mental health status was assessed using the Cornell Medical Index (CMI) self-assessment questionnaire. Sixty-four PD patients exhibiting neuropsychiatric symptoms were selected for the controlled study and randomly grouped into treatment and control groups. The treatment group received BoNT/A injections, while the control group received a placebo. The primary outcome measures included depression scores from the CMI and the proportion of patients displaying improvement in neuropsychiatric symptoms at 8 weeks post-treatment. The secondary outcome was other CMI scores at 4, 8, and 12 weeks post-treatment.ResultsThe outcomes revealed that PD patients had significantly higher scores in various neuropsychiatric factors compared to healthy controls. At 4 weeks post-treatment, the treatment group displayed improvements in depression and tension. At 8 weeks post-treatment, they exhibited significant reductions in depression, anxiety, sensitivity, and tension compared to the control group. Moreover, a notably higher percentage of patients in the treatment group showed improvement in neuropsychiatric symptoms compared to the control group. At 12 weeks post-treatment, the treatment group exhibited significant improvements in somatization, depression, sensitivity, and tension.ConclusionPD patients commonly experience multiple neuropsychiatric symptoms, and BoNT/A has demonstrated efficacy in alleviating these symptoms. Specifically, BoNT/A was found to effectively alleviate somatization, tension, anxiety, depression, and sensitivity in PD patients.

ObjectiveTo determine the association between antipsychotic prescriptions and incident dementia in patients with schizophrenia or schizoaffective disorder.MethodsIn this retrospective cohort study, Cox Proportional hazard models estimated the association between antipsychotic prescriptions and incident dementia in participants ≥50 years of age with a schizophrenia/schizoaffective disorder diagnosis over 12 years. Confounding was controlled by E-balance.ResultsCumulative dementia incidence was significantly greater among those with an antipsychotic prescription compared to those without (7.9% vs 5.5%, P < 0.0001). After controlling for confounding, antipsychotic prescriptions were associated with a 92% increased risk for dementia (HR = 1.92; 95% CI:1.13-3.27). This association was not significant among those aged ≥65 years. Antipsychotic prescription type (eg, first generation, yes or no) did not affect dementia risk but prescription number did.ConclusionAntipsychotic prescriptions were associated with almost twice the incidence of dementia compared to patients without in those with schizophrenia/schizoaffective disorder.

ObjectiveThis study aims to examine educational heterogeneity in the relationship between internet use and episodic memory among older adults in China, within the context of advancing Chinese modernization.MethodsData from the 2018 and 2020 waves of China Health and Retirement Longitudinal Study (CHARLS) were used for analysis. By employing a longitudinal study design with lagged predictors and the inverse probability of treatment weighting (IPTW) approach alongside its extension-the marginal structural model (MSM) for sufficient cause interactions-this study mitigated potential reverse causality and self-selection biases related to internet use and educational attainment.ResultsThe findings indicate a significant positive longitudinal association between internet use and delayed word recall in older women, incorporating delayed and immediate recall scores at baseline as covariates for predicting propensity scores of internet use. Additionally, the preservation of delayed word recall linked to internet use was more pronounced among older women with less than an elementary school education. Doubly robust estimation results further confirmed the reliability of the core findings. Furthermore, we investigated the longitudinal associations between specific online activities and episodic memory. The results show that posting on social media and engaging in online chatting positively correlated with episodic memory in older women, whereas browsing news online was positively associated with episodic memory in older men.ConclusionThese findings support the cognitive enrichment hypothesis, which asserts that internet use serves as a mentally stimulating activity that may help delay cognitive aging, especially among individuals with limited cognitive stimuli.

BackgroundPsychosis occurs in approximately 41% of patients living with Alzheimer's disease. Previous findings from our group based on analyses of a neuropathological cohort suggest that among AD patients with Lewy Body pathology, female APOE4 homozygotes are at significantly greater risk of psychosis. This study aims to replicate this finding in a clinical cohort using data from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset.MethodsOur group used data from a sample of patients with AD in the ADNI database from the ADNI1, ADNI2, ADNI3, and ADNIGO studies. We defined psychosis status as experiencing hallucinations or delusions at one time point based on the Neuropsychiatric Inventory. We then used forward binary logistic regression to determine if sex and APOE4 status are predictors of AD + P.ResultsIn total there were 204 participants who met the inclusion criteria, 133 of which were male, and 71 of which were female. Fifty-six patients were APOE4 non-carriers, 109 patients were APOE4 heterozygote carriers, and 39 were APOE4 homozygote carriers. In total, there were 59 patients with psychosis. When adjusting for mini mental state examination score, adjusted hippocampal volume, and age, we demonstrate that female APOE4 homozygotes have a significantly increased risk of psychosis compared to other groups (P = 0.0264, OR = 19.50).DiscussionThe results of our study demonstrate a significant association between psychosis risk and female APOE4 homozygotes, thus corroborating findings from a neuropathological cohort. The effects of APOE ε4 on psychosis risk are significant only in females, and not in males.

BackgroundWomen with Parkinson's disease (PD) are less likely to have a caregiver.ObjectiveTo determine factors contributing to gender disparities in PD caregiving.MethodsWe conducted a cross-sectional survey of people with PD and caregivers participating in the Parkinson's Foundation Parkinson's Outcomes Project and compared patient and caregiver characteristics by gender.ResultsAmong PD patients, 20.7% of 1663 women and 14.2% of 3005 men had no caregiver (P < 0.001). Women without caregivers were older (69.1 vs 66.3, P < 0.001), less likely to be married (30.4% vs 54.7%, P < 0.001), and more likely to be taking an antidepressant (41.8% vs 30.9%, P = 0.002) than men. Using stepwise logistic regression models, gender differences in access to caregiving were explained by marital status. Among caregivers, women reported more strain (P < 0.001) and had less time for other family members (P < 0.001).ConclusionFewer women with PD have caregivers because they are less likely to have a spouse.

BackgroundHearing loss has been related to impaired cognition among older adults. The cost effectiveness of existing hearing support tools is controversial. Other potential modifying strategies that could effectively intervene in this prevalent and far-reaching association between hearing loss and cognitive decline remain unclear. This study aimed to narratively and quantitatively synthesize the mediators and moderators involved in the link between hearing loss and cognitive impairment from a psycho-social and physical point of view.MethodWe searched 6 databases for articles exploring mediating or moderating associations of hearing loss-cognition association from inception to March, 2024. Data were synthesized narratively and quantitatively by meta-analytic approaches.ResultsThe search yielded 63 included studies. Social (social engagement, social support, age, sex, ethnicity, cognitive reserve)-psycho (depression, anxiety, loneliness, resilience)-physical (cardiovascular diseases and risk factors, perceived health, disability, APOE carrier, vision impairment, gait speed) variables mediated or moderated the relationship between hearing loss and cognitive impairment to varying degrees. Subgroup analyses identified susceptible populations at greater risk for cognitive decline, including women, younger elders with hearing loss, and older adults with dual sensory loss.ConclusionCombined interventions targeting these modifiable variables across psycho-social and physical dimensions may be more cost-effective for intervening in the ensemble of hearing loss-cognitive impairment in older adults.