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.

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.

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.

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.

Background: Forced migration results in exposure to trauma, interrupted access to healthcare, and loss of social support and may increase dementia risk. Literature on refugees' knowledge of dementia and its risk factors is scant. This study investigates refugee perspectives on dementia and their access to cognitive healthcare in the United States (US).

Methods: We conducted 6 focus groups and 30 individual in-depth interviews (total of 69 participants) with Arab, African, and Afghan refugees resettled in San Diego, California. Data was coded using inductive thematic analysis.

Results: Organized by the socioecological model of health, the following themes emerged: (1) mental trauma due to migration was linked to dementia (individual); (2) fear of dementia and burdening caregivers due to limited support systems (interpersonal); (3) reliance on virtual communities for dementia information and the stress of local community loss increasing dementia risk (community); (4) healthcare providers, both in the US and in refugee camps, didn't address cognitive health concerns (institutions); and (5) discriminatory immigration and healthcare policies as barriers to healthy aging (policy).

Discussion: Despite being a heterogeneous group, refugees share specific experiences, knowledge gaps, and barriers to healthy aging. Tailored interventions and policies are needed to address this population's cognitive health needs. This includes addressing their mental health and social support concerns as well as training clinicians to screen for/discuss dementia with aging refugee patients.

Background: Pyridostigmine is hypothesized to improve neurogenic orthostatic hypotension (nOH) symptoms without causing or exacerbating supine hypertension. The objective of this review was to evaluate the safety and efficacy of pyridostigmine for management of nOH.

Methods: A literature search of PubMed, Embase, and CENTRAL was performed in December 2023 for prospective trials with a placebo or active comparator.

Results: Four randomized and two non-randomized studies were reviewed. Three studies utilizing a single dose, crossover design found significant differences of orthostatics using adjunctive pyridostigmine. Two studies assessing longer-term endpoints demonstrated conflicting efficacy of pyridostigmine with one trial finding significant improvement in orthostatics and symptoms after three months of therapy. Use of pyridostigmine did not lead to supine hypertension with most adverse effects being cholinergic.

Conclusion: Pyridostigmine may be considered as an adjunctive medication in individuals with nOH refractory to standard treatment options as it carries a favorable safety profile with low risk for supine hypertension.

Background: Studies have examined the association between dual sensory impairment and late-life cognitive outcomes in the U.S with inconsistent findings.

Objective: To examine the associations between sensory impairment and 10-year risk of dementia or Alzheimer's disease among U.S. adults aged ≥ 50.

Methods: A prospective cohort study based on the Health and Retirement Study from 2010 to 2020. Individuals aged ≥ 50 years without self-reported dementia and Alzheimer's disease in 2010 were included in the analysis. Self-reported visual and hearing impairments were measures in 2010. Main failure events included self-reported incident dementia and Alzheimer's disease over a 10-year follow-up period. Participants were categorized as having no visual or hearing impairment, visual impairment only, hearing impairment only, and dual sensory impairment. Fine-Gray competing risk regression model was applied to estimate the associations of sensory impairment with incident dementia and Alzheimer's disease, adjusted for demographic characteristics, health behaviors, and health conditions at baseline.

Results: Of 20,248 identified individuals, 14.6% had visual impairment only, 11.2% had hearing impairment only, and 9.1% had dual impairment at baseline. After adjusting for all covariates, dual sensory impairment was associated with higher risk of dementia (HR = 1.46, 95% CI: 1.23-1.73) and Alzheimer's disease (HR = 1.35, 95% CI: 1.03-1.76). Visual impairment only was also associated with incident dementia and Alzheimer's disease among individuals <65 years.

Conclusion: Older adults in the U.S. with visual and hearing impairments simultaneously had a particularly greater risk of dementia and Alzheimer's disease, indicating the needs of targeted screening for timely treatment and further prevention of dementia and Alzheimer's disease.

Objective: Social factors can influence the brain's dopaminergic function. This study investigated the relationship between socioenvironmental factors and dopamine transporter (DaT) availability in healthy individuals (n = 74) and those with Parkinson's disease (PD) (n = 240).

Methods: All single photon emission computed tomography (SPECT) DaT data and clinical data used in this study were obtained from the Parkinson's Progression Markers Initiative (PPMI) dataset. Socioenvironmental data was obtained from Social Explorer analyses of the American Community Survey (2014-2018) using the residential ZIP codes of the subjects available in the PPMI dataset.

Results: Participants resided in 302 ZIP code tabulation areas across 38 U.S. states. In healthy individuals, DaT signals were significant and negatively correlated in the caudate with median household income (r = -0.27, P = 0.02) and educational level of the living area (r = -0.23, P = 0.04), but not significant in the putamen (r = -0.21, P = 0.08; r = -0.11, P = 0.37 respectively). Also, there was a significant positive correlation between DaT signals in caudate and poverty rates (r = 0.29, P = 0.01), but not in the putamen (r = 0.16, P = 0.19) in healthy subjects. No significant associations were observed in the PD group for any variables.

Conclusion: The study findings suggest that socioenvironmental factors, such as median household income, education level, and poverty rate, are significantly associated with DaT availability in the caudate of healthy individuals but not in those with PD. This indicates that PD might disrupt the connection between the social environment and dopaminergic function. These results underscore the importance of considering socioenvironmental variables when studying dopaminergic function in the human brain.