Neuropsychiatric Distress Research Articles

Safe, Social, and Engaged: Clinician perspectives on good institution‐free days for people with dementia

AbstractBackgroundComposite measures of survival and residence, such as institution‐free days (IFDs), encompass many patient and family priorities and are readily measured using payer claims or electronic health record data. However, knowledge gaps limit their application to studies of people with dementia (PWD). First, PWD, family care partners, and clinician perspectives on survival‐residence composite outcomes are unknown. Second, approaches to measuring IFDs consider all institution days equally poor and all home days equally well, which may be inconsistent with stakeholder assessments.MethodWe conducted a qualitative study to explore stakeholders’ perspectives on what makes a “good day” for a PWD. This included semi‐structured interviews with clinicians who provide care to PWD. Clinicians were also asked for their opinions regarding the use of survival‐residence composite outcomes in dementia research. Interviews were audio‐recorded and professionally transcribed. De‐identified transcripts were reviewed by the research team independently and during weekly consensus meetings to identify relevant themes.ResultThematic saturation was reached after 24 interviews. Nearly half of clinicians also had personal experience as a care partner of a PWD. Participant characteristics are summarized in Table 1. Salient themes were identified and grouped into 2 major categories: (1) attributes of quality of days for PWD, and (2) impressions of survival‐residence composite outcomes (Table 2). Key attributes of quality of days were safety, socialization and engagement, and neuropsychiatric distress. These qualities were more important in defining “home” than type of residence (Figure). Clinicians appreciated that a survival‐residence composite outcome, such as IFDs, could capture the important aspects of “aging in place” and avoiding burdensome hospitalizations. They also noted a desire for such a measure to capture the quality of those days. Concerns were raised over how differential access to home‐based services due to socioeconomic factors would influence patient accrual of IFDs and whether such a measure might also increase existing stigma around institutions.ConclusionFuture work will integrate these findings with the perspectives of PWD and their family care partners as well as further explore the relative values of these attributes of a survival‐residence composite outcome for studies of patients with ADRD.

Legacy of neuropsychiatric symptoms associated with past COVID-19 infection: A cause of concern.

Although primarily affecting the respiratory system, growing attention is being paid to the neuropsychiatric consequences of severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2) infections. Acute and sub-acute neuropsychiatric manifestations of coronavirus disease 2019 (COVID-19) disease and their mechanisms are better studied and understood currently than they had been when the pandemic began; however, many months or years will be necessary to fully comprehend how significant the consequences of such complications will be. In this editorial, we discuss the possible long-term sequelae of the COVID-19 pandemic, deriving our considerations on experiences drawn from past coronaviruses’ outbreaks, such as the SARS and the middle east respiratory syndrome, and from the knowledge of the mechanisms of neurotropism and invasiveness of SARS-CoV-2. Acknowledging the global spread of COVID-19 and the vast number of people affected, to date amounting to many millions, the matter of this pandemic’s neuropsychiatric legacy appears concerning. Public health monitoring strategies and early interventions seem to be necessary to manage the possible emergence of a severe wave of neuropsychiatric distress among the survivors.

Further evidence on the interplay between benzodiazepine and Z-drug abuse and emotion dysregulation

Background: Long-term benzodiazepine (BDZ)/Z-drug use, which is a risk factor for dependence, is frequent in neuropsychiatric conditions, especially emotional disorders. Also, BDZ/Z-drug misuse is associated with increased emotion dysregulation symptoms. This study aimed to investigate neuropsychiatric distress in patients with BZD/Z-drug use disorder, with particular attention to emotional symptoms. Methods: Forty-two patients hospitalized for BZD/Z-drug use disorder (males/females= 20/22) were enrolled and dichotomized into a high-dose and a low-dose BZD/Z-drug user group. Neuropsychiatric distress was measured using standardized measures. The relationship between symptom profiles and BZD/Z-drug use disorder severity was explored using t-tests and negative binomial regression analyses. Results: Twenty-seven patients (61.9%) presented with one or more psychiatric disorders, mostly an emotional disorder. Ten patients had a lifetime history of suicide attempt(s) (23.8%), while 11 presented recent suicidal ideation (26.2%), which resulted in suicidal behavior in 2 cases. High rates of depression, anxiety, and emotion dysregulation were reported. The high-dose BZD/Z-drug user group presented with higher depressive symptoms (p = 0.016) and emotion dysregulation (p = 0.044) than the low-dose BZD/Z-drug user group. Further, the higher the depressive symptomatology, the more severe was the BZD/Z-drug abuse (p = 0.028). Limitations: Long-term patterns of BDZ/Z-drug use disorder among patients with emotional disorders and the role of other potential risk factors, such as gender, other substance use disorder, and personality disorders, need further investigation in larger samples. Conclusions: This study showed high emotional symptoms among patients with BZD/Z-drug use disorder, with severe depression being associated with a more severe BZD/Z-drug dependence.

Interventional Study to Evaluate the Clinical Effects and Safety of the Nutraceutical Compound BrainUp-10® in a Cohort of Patients with Alzheimer's Disease: A Multicenter, Randomized, Double-Blind, and Placebo-Controlled Trial.

Clinically-evaluated nutraceuticals are candidates for Alzheimer's disease (AD) prevention and treatment. Phase I studies showed biological safety of the nutraceutical BrainUp-10®, while a pilot trial demonstrated efficacy for treatment. Cell studies demonstrated neuroprotection. BrainUp-10® blocks tau self-assembly. Apathy is the most common of behavioral alterations. The aim was to explore efficacy of BrainUp-10® in mitigating cognitive and behavioral symptoms and in providing life quality, in a cohort of Chilean patients with mild to moderate AD. The was a multicenter, randomized, double blind, placebo-controlled phase II clinical study in mild to moderate AD patients treated with BrainUp-10® daily, while controls received a placebo. Primary endpoint was Apathy (AES scale), while secondary endpoints included Mini-Mental State Examination (MMSE), Trail Making Test (TMT A and TMT B), and Neuropsychiatry Index (NPI). AD blood biomarkers were analyzed. Laboratory tests were applied to all subjects. 82 patients were enrolled. The MMSE score improved significantly at week 24 compared to baseline with tendency to increase, which met the pre-defined superiority criteria. NPI scores improved, the same for caregiver distress at 12th week (p = 0.0557), and the alimentary response (p = 0.0333). Apathy tests showed a statistically significant decrease in group treated with BrainUp-10®, with p = 0.0321 at week 4 and p = 0.0480 at week 12 treatment. A marked decrease in homocysteine was shown with BrainUp-10® (p = 0.0222). Data show that BrainUp-10® produces a statistically significant improvement in apathy, ameliorating neuropsychiatric distress of patients. There were no compound-related adverse events. BrainUp-10® technology may enable patients to receive the benefits for their cognitive and behavioral problems.

The Emerging Role of Nutraceuticals and Phytochemicals in the Prevention and Treatment of Alzheimer's Disease.

One of the major challenges of medical sciences has been finding a reliable compound for the pharmacological treatment of Alzheimer's disease (AD). As most of the drugs directed to a variety of targets have failed in finding a medical solution, natural products from Ayurvedic medicine or nutraceutical compounds emerge as a viable preventive therapeutics' pathway. Considering that AD is a multifactorial disease, nutraceutical compounds offer the advantage of a multitarget approach, tagging different molecular sites in the human brain, as compared with the single-target activity of most of the drugs used for AD treatment. We review in-depth important medicinal plants that have been already investigated for therapeutic uses against AD, focusing on a diversity of pharmacological actions. These targets include inhibition of acetylcholinesterase, β-amyloid senile plaques, oxidation products, inflammatory pathways, specific brain receptors, etc., and pharmacological actions so diverse as anti-inflammatory, memory enhancement, nootropic effects, glutamate excitotoxicity, anti-depressants, and antioxidants. In addition, we also discuss the activity of nutraceutical compounds and phytopharmaceuticals formulae, mainly directed to tau protein aggregates mechanisms of action. These include compounds such as curcumin, resveratrol, epigallocatechin-3-gallate, morin, delphinidins, quercetin, luteolin, oleocanthal, and meganatural-az and other phytochemicals such as huperzine A, limonoids, azaphilones, and aged garlic extract. Finally, we revise the nutraceutical formulae BrainUp-10 composed of Andean shilajit and B-complex vitamins, with memory enhancement activity and the control of neuropsychiatric distress in AD patients. This integrated view on nutraceutical opens a new pathway for future investigations and clinical trials that are likely to render some results based on medical evidence.

Neuropsychiatric Symptoms in Patients with Idiopathic Rapid Eye Movement Sleep Behavior Disorder

Background and Objective Idiopathic rapid eye movement sleep behavior disorder (IRBD) is a strong predictor of the development of synucleinopathies, including Parkinson’s disease. Neuropsychiatric symptoms are common in patients with Parkinson’s disease but have not been properly evaluated in IRBD. We used the Symptom Checklist-90-Revision (SCL-90-R) to evaluate the symptom profile of patients with drug-naïve IRBD. Methods Consecutive drug-naïve patients with video-polysomnography-confirmed IRBD that visited Kyung Hee University Hospital at Gangdong sleep clinic January 2009–November 2016 were reviewed. Age- and sex-matched healthy volunteers served as controls. Questionnaires evaluating sleep [Pittsburgh sleep quality index (PSQI) and insomnia severity index (ISI)] and depression [beck depression inventory-II (BDI-II)] were conducted with the SCL-90-R in IRBD patients and controls. Results Twenty patients with IRBD and 20 age- and sex-matched controls were analyzed. In IRBD patients, the mean age was 59.5, 55% were male, and the mean disease duration was 55.1 months. PSQI scores (5.7 ± 2.2 vs. 3.2 ± 1.4, p < 0.0001) and ISI scores (11.2 ± 8.7 vs. 4.1 ± 3.4, p < 0.0001) were higher in patients with IRBD than in the controls. Three IRBD patients (15%) had abnormal SCL-90-R T-scores over 70. The T-scores for phobic anxiety (p=0.009), interpersonal sensitivity (p = 0.011), psychoticism (p = 0.013), hostility (p = 0.014), anxiety (p = 0.020), and depression (p = 0.049) were higher in the patients. After adjusting for age, BDI-II scores were positively correlated with RBD disease duration (r = 0.484, p = 0.042) in IRBD patients. Conclusions The results of our study demonstrate that neuropsychiatric distress is more severe in patients with IRBD with no comorbidities than in otherwise healthy individuals. Key words: REM sleep behavior disorder, Neuropsychiatric symptom, SCL-90-R.

Decoding and Treating Neuropsychiatric Symptoms in Dementia

In assessing the neuropsychiatric symptoms of patients with dementia, Laura C. Hanson, MD, MPH, a professor in the division of geriatric medicine at the University of North Carolina at Chapel Hill, said one of her main teaching points is to avoid use of the nonspecific term “agitation.” “The term I use is physical restlessness or emotional restlessness, which I find to be at least slightly more descriptive than agitation ... We can better work [from there] on identifying underlying factors,” Dr. Hanson said during a dementia panel discussion at the annual meeting of the American Geriatrics Society. Some 85% of individuals with moderate to severe dementia experience neuropsychiatric symptoms, which can be caused by environmental triggers, distressing caregiver behaviors, lack of stimulation, physical pain, or other factors. “We know from a variety of descriptive studies that a very high percentage of people with even moderate and later-stage dementia are able to self-report pain,” she emphasized. Words are easier than numbers, however. “It is not worth asking them to rate their pain on a 1 to 10 scale. But they can answer the question, ‘Are you in pain now?’ or ‘Are you in discomfort now?’ They may respond better [to the word] discomfort,” she said. “Ask slowly — they may need time to answer. And we need to use our clinical observation skills.” At least one well-designed randomized controlled trial — a Norwegian trial of 352 nursing home residents — has shown that treating pain improves neuropsychiatric distress in patients with moderate to severe dementia, Dr. Hanson said. The residents randomized to an individualized stepwise pain treatment protocol beginning with an acetaminophen equivalent and “moving all the way [if necessary] to low-dose opioids” were more likely to have significant reductions in pain, agitation, and psychiatric symptoms than residents who received usual care (BMJ 2011;343:d4065). These findings “suggest there is a strong linkage between some neuropsychiatric distress and pain,” Dr. Hanson said. Depression should also be considered when neuropsychiatric symptoms are reported — they affect 25% of individuals with early-stage Alzheimer’s and significantly more who have vascular dementia — as should akathisia and psychosis in some cases. “I often ask myself, is it akathisia, a neurologic syndrome of physical restlessness that could be a side effect of an antipsychotic?” Dr. Hanson said. “And I also ask, are there psychotic symptoms involved, which could in some cases point to a medical delirium?” Unfortunately, “with depression, the treatment evidence is inconclusive for our ability to intervene with traditional SSRIs or other antidepressants,” she said. “Probably the most important evidence-based point is to avoid benzodiazepines when a person is expressing anxiety and sadness and has underlying dementia.” Otherwise, the treatment of neuropsychiatric symptoms is about symptom management with nonpharmacologic interventions. “Begin with decoding internal or environmental triggers for distress and reversing them,” she advised. Then use music, aroma, and other sensory modalities; most of these nonpharmacologic interventions are supported by moderate-quality evidence. Christine Kilgore is a freelance writer in Falls Church, VA.

Substance use is a risk factor for neurocognitive deficits and neuropsychiatric distress in acute and early HIV infection

The acute and early stages of HIV infection (AEH) are characterized by substantial viral replication, immune activation, and alterations in brain metabolism. However, little is known about the prevalence and predictors of neurocognitive deficits and neuropsychiatric disturbances during this period. The present study examined the impact of demographic, HIV disease, and substance use factors on HIV-associated neurocognitive impairment and self-reported neuropsychiatric distress among 46 antiretroviral-naive adults with median duration of infection of 75days relative to a sample of 21 HIV seronegative (HIV-) adults with comparable demographics and risk factors. Participants were administered a brief neurocognitive battery that was adjusted for demographics and assessed executive functions, memory, psychomotor speed, and verbal fluency, as well as the Profile of Mood States, a self-report measure of neuropsychiatric distress. Odds ratios revealed that AEH participants were nearly four times more likely than their seronegative counterparts to experience neurocognitive impairment, particularly in the areas of learning and information processing speed. Similarly, AEH was associated with a nearly fivefold increase in the odds of neuropsychiatric distress, most notably in anxiety and depression. Within the AEH sample, HIV-associated neurocognitive impairment was associated with problematic methamphetamine use and higher plasma HIV RNA levels, whereas neuropsychiatric distress was solely associated with high-risk alcohol use. Extending prior neuroimaging findings, the results from this study indicate that HIV-associated neurocognitive impairment and neuropsychiatric distress are highly prevalent during AEH and are associated with high-risk substance use.

Executive Dysfunction and Neuropsychiatric Symptoms Predict Lower Health Status in Essential Tremor

To evaluate the hypothesis that increased neuropsychiatric distress and cognitive impairment are associated with lower perceived health status in essential tremor (ET). Many patients with ET experience nonmotor complications, including lower perceived health status and poor health-related quality of life, which are associated with tremor severity, age, and personality factors. No studies, however, have examined the potential contribution of neuropsychiatric symptoms and cognitive deficits to health status in ET. Forty-five patients with ET underwent comprehensive neurologic and neuropsychologic evaluations, including self-report measures of physical and psychosocial health status (ie, the Sickness Impact Profile) and neuropsychiatric distress (ie, the Profile of Mood States). A series of hierarchical multiple regressions showed that after considering the effects of ET disease severity, lower vigor, and deficits in executive functions were independently predictive of poorer physical health status, whereas increased symptoms of depression were uniquely associated with lower psychosocial health status. Findings indicate that reduced vigor (ie, apathy), executive deficits, and depression are important predictors of poorer perceived health status in ET. Given the prevalence of such nonmotor symptoms, these data highlight the potential value of considering neuropsychiatric and neurocognitive assessments in the management of patients with ET.