Heterogeneity of Response to Methylphenidate in Apathetic Patients in the ADMET 2 Trial.

OBJECTIVE: The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2) found that methylphenidate was effective in treating apathy with a small-to-medium effect size but showed heterogeneity in response. We assessed clinical predictors of response to help determine individual likelihood of treatment benefit from methylphenidate. DESIGN: Univariate and multivariate analyses of 22 clinical predictors of response chosen a priori. SETTING: Data from the ADMET 2 randomized, placebo controlled multi-center clinical trial. PARTICIPANTS: Alzheimer's disease patients with clinically significant apathy. MEASUREMENTS: Apathy assessed with the Neuropsychiatric Inventory apathy domain (NPI-A). RESULTS: In total, 177 participants (67% male, mean [SD] age 76.4 [7.9], mini-mental state examination 19.3 [4.8]) had 6-months follow up data. Six potential predictors met criteria for inclusion in multivariate modeling. Methylphenidate was more efficacious in participants without NPI anxiety (change in NPI-A -2.21, standard error [SE]:0.60) or agitation (-2.63, SE:0.68), prescribed cholinesterase inhibitors (ChEI) (-2.44, SE:0.62), between 52 and 72 years of age (-2.93, SE:1.05), had 73-80 mm Hg diastolic blood pressure (-2.43, SE: 1.03), and more functional impairment (-2.56, SE:1.16) as measured by the Alzheimer's Disease Cooperative Study Activities of Daily Living scale. CONCLUSION: Individuals who were not anxious or agitated, younger, prescribed a ChEI, with optimal (73-80 mm Hg) diastolic blood pressure, or having more impaired function were more likely to benefit from methylphenidate compared to placebo. Clinicians may preferentially consider methylphenidate for apathetic AD participants already prescribed a ChEI and without baseline anxiety or agitation.

A geriatrics walking clinic improves hemoglobin A1c and timed gait in older veterans with type 2 diabetes.

Over one quarter of older adults in the U.S. has diabetes; and, physical activity is important for the promotion of healthy aging in this population. The purpose of this clinical demonstration project is to evaluate the effect of physical activity in the form of walking on glycemic control and timed gait in older Veterans with type 2 diabetes (T2D). Veterans aged ≥60 years were enrolled in the Geriatrics Walking Clinic (GWC), a clinical demonstration project, at South Texas Veterans Health Care System. GWC is a 6-week clinical program that promotes physical activity and is delivered by a registered nurse/diabetes educator and geriatrician. Veterans were recruited from the VA clinics. Enrolled patients received a pedometer at an initial face-to-face visit, were followed with weekly phone calls to monitor steps/day, received encouragement, and participated in a final face-to-face visit at the end of 6 weeks. In a sub-set of patients with T2D, we performed a chart review and recorded Hemoglobin A1c (HbA1c) at 3, 6, and 12 months after completion of the program. Timed Gait, a major characteristic of frailty, was measured at baseline and after completing the program. Change in HbA1c and timed gait compared to baseline was examined using paired t-tests. Sixty-two patients had HbA1c values available and were included in this analysis. Of these, 36, 52, and 61 patients had repeat HbA1c at 3, 6, and 12 months after the intervention, respectively. Mean age was 68 ± 6 years, 58% were Hispanic, and 92% males. HbA1c improved at 3 months (-0.49, 95% CI: -0.87 to -0.12, p=0.013), at 6 months (-0.40, 95% CI: -0.68 to -0.12, p=0.006), and at 12 months (-0.30, 95% CI: -0.57 to -0.029, p=0.031) compared to baseline. Timed Gait also improved (9.3 ±1.7 vs. 10.2 ±1.8, p<0.001). The finding highlights that older patients with T2D benefit from a GWC with improved glycemic control and timed gait.

VA Video Connect for Clinical Care in Older Adults in a Rural State During the COVID-19 Pandemic: Cross-Sectional Study.

BACKGROUND: The COVID-19 pandemic has accelerated the need for telehealth at home. Although the Department of Veterans Affairs is a leading provider of telehealth, disparities may exist in reaching older veterans living in rural areas. VA Video Connect (VVC) is a video conferencing app that enables veterans to connect with their health care provider via a secure and private session. OBJECTIVE: The aim of this study was to examine the capability and willingness of older veterans to participate in a VVC visit during the COVID-19 pandemic. METHODS: A cross-sectional study was conducted on older veterans (N=118) at the Central Arkansas Veterans Healthcare System. Participants were interviewed over the phone and responses to the following items were recorded: availability of internet, email, and an electronic device with a camera; veterans' willingness to complete an appointment via a VVC visit; and availability of assistance from a caregiver for those who were unable to participate in a VVC visit alone. RESULTS: Participants' mean age was 72.6 (SD 8.3) years, 92% (n=108) were male, 69% (n=81) were Caucasian, 30% (n=35) were African Americans, and 36% (n=42) lived in a rural location. The majority reported having access to the internet (n=93, 77%) and email service (n=83, 70%), but only 56% (n=67) had a camera-equipped device. Overall, 53% (n=63) were willing and capable of participating in a VVC visit. The availability of internet access was significantly lower in rural compared to nonrural participants (P=.045) and in those with or less than a high school education compared to those who pursued higher education (P=.02). Willingness to participate in the VVC visit was significantly lower in rural compared to nonrural participants (P=.03). Of the participants who reported they were able and willing to partake in a VVC visit (n=54), 65% (n=35) opted for VVC and 35% (n=19) preferred a phone visit. In total, 77% (n=27) of the scheduled VVC visits were successful. CONCLUSIONS: Despite advances in technology, and willingness on the part of health care systems, there are some lingering issues with capability and willingness to participate in video telehealth visits, particularly among older adults residing in rural areas.

Association of chronic obstructive pulmonary disease with mild cognitive impairment and dementia.

PURPOSE OF REVIEW: As age expectancy increases, both dementia and chronic obstructive pulmonary disease (COPD) have become more prevalent. Dementia and COPD together, however, occur more commonly than would be predicted from the incidence of either alone, suggesting a link between these two common senescent diseases. The purpose of this article is to review the extant literature and report findings in a clinically meaningful manner. We will look at the level of evidence, the risk factors for co-occurrence of the two diseases and the differential effects upon cognitive domains in the population with dementia and COPD. RECENT FINDINGS: Cognitive impairment in patients with COPD may be 'dose-dependent' with the duration of COPD. Patients with COPD appear to develop nonamnestic mild cognitive impairment (MCI) as opposed to amnestic MCI. Newer studies exploring the impact of oxygen therapy and pulmonary rehabilitation upon cognitive function have reported some positive findings. SUMMARY: Higher prevalence of MCI/dementia is seen in patients with COPD compared with age-matched controls. Imaging findings and dementia/MCI biomarkers provide preliminary evidence for an indirect association of the two conditions. Although no causality can be drawn with the available data, there is some indication that the severity of hypoxemia correlates with the severity of cognitive dysfunction.

Topiramate Monotherapy for Civilian Posttraumatic Stress Disorder: A Controlled Pilot Study.

Objective: To assess the efficacy, safety, and tolerability of topiramate for the treatment of posttraumatic stress disorder (PTSD) in civilians.Methods: This 12-week double-blind, randomized, placebo-controlled study enrolled 72 outpatients (aged 19-64 years) with a DSM-IV-TR diagnosis of non-combat-related PTSD and a score ≥ 50 on the Clinician-Administered PTSD Scale (CAPS). The primary efficacy endpoint, percent change in total CAPS score, and secondary efficacy measures were assessed by analysis of covariance. Safety assessments included monitoring of vital signs, physical examinations, clinical laboratory parameters, electrocardiograms, and adverse events (AEs). The study was conducted from October 2001 to March 2004.Results: The intent-to-treat (ITT) population (N = 68; mean age = 35 years; 87% women; 74% White) showed greater percent reduction in total CAPS scores with topiramate versus placebo (39.5% vs 29.5%), but the difference was not statistically significant (P = .31). Similarly, higher reductions with topiramate versus placebo were seen in the CAPS subscale scores for symptoms of reexperiencing (43.6% vs 34.8%), avoidance/numbing (38.3% vs 30.6%), and hyperarousal (36.6% vs 21.4%). However, these differences were not statistically significant. Six patients in the topiramate arm had a final CAPS score < 20, whereas only 2 in the placebo arm achieved the result (P = .075). The median final topiramate daily dose was 100 mg/d (range, 25-400 mg/d), and mean ± SD treatment duration was 55 ± 32 days, showing the tolerability of the medication. In topiramate-treated patients, treatment-emergent AEs included paresthesia, headache, fatigue, and insomnia; treatment-limiting AEs included influenza-like symptoms, agitation, cognitive problems not otherwise specified, and somnolence. However, a higher rate of AE-related discontinuation was seen in the placebo group than in the treatment group (26% vs 18%).Conclusions: In this 12-week civilian PTSD study, topiramate improved the primary and secondary outcome measures at a higher rate than did placebo, but the difference did not reach statistical significance. Further adequately powered studies may be warranted.Trial Registration: Clinical Trials.gov identifier: NCT00208130.Prim Care Companion CNS Disord 2023;25(5):23m03555. Author affiliations are listed at the end of this article.

Reversal of SSRI-associated apathy syndrome by discontinuation of therapy.

OBJECTIVE: To report 6 cases of selective serotonin reuptake inhibitor (SSRI)-associated apathy syndrome. CASE SUMMARIES: In all 6 cases, the patient reported loss of motivation while being treated with an SSRI. Loss of motivation was of new onset and temporally associated with the use of the SSRI. A trial of discontinuation of the SSRI was performed in all 6 patients and 2 were started on bupropion while cross-tapering from the SSRI. During the treatment trials, depression and apathy were monitored in all patients. Each case was assessed using the Apathy Evaluation Scale, Clinician version (AES-C), and by evaluating how the patient responded to discontinuation of the SSRI. DISCUSSION: Scores on the AES-C improved significantly in all 6 cases after the SSRI was discontinued. Improvement was also seen in the motivation, novelty, and persistence subdomain scores of the AES-C. A pretreatment AES-C score was available only in the first case. Based on the Naranjo probability scale, there was a probable cause of apathy syndrome with SSRI therapy in the first case and a possible association in the rest of the cases. CONCLUSIONS: In some patients SSRIs may cause an apathy syndrome that can be reversed through discontinuation of the agent. When evaluating patients being treated with an SSRI, clinicians should have a high degree of suspicion and specifically inquire for this iatrogenic form of apathy syndrome.

Veterans Affairs Health Care Provider Perceptions of Virtual Reality: Brief Exploratory Survey.

BACKGROUND: Virtual reality (VR), a simulated experience that can be similar to or completely different from the real world, has become increasingly useful within the psychiatric and medical fields. This VR technology has been applied in medical school trainings, exposure therapy for individuals with posttraumatic stress disorder (PTSD), and reminiscence therapy associated with mood disorders for older adults. Perceptions of VR through the lens of the health care provider require further exploration. VR has grown in popularity; however, this modality continues to be underused in most Veterans Affairs (VA) hospitals. OBJECTIVE: A web-based survey was used to explore health care provider perceptions of immersive VR availability and use for older adults and identify potential barriers for immersive VR use in older adults with cognitive impairment. METHODS: An 8-item web-based survey was developed to obtain health care provider feedback. This survey was disseminated throughout a single Veterans Integrated Services Network (VISN). The VR survey was developed via the Survey Monkey platform and distributed through the secure VA email network. Providers were asked to voluntarily participate in the brief, anonymous survey and offer their perceptions of immersive VR use within their patient population. Survey data were reviewed and interpreted using descriptive statistics. RESULTS: A total of 49 respondents completed the survey over a 15-day period. Of them, 36 respondents (73%) had heard of a VR device, though the majority (n=44, 90%) had never used or prescribed a VR device. Respondents identified several potential barriers to immersive VR use in older adults with cognitive impairment (eg, hearing difficulties, perceptions of technology, cognitive concerns, access to resources, and visual impairment). Despite the barriers identified, providers (n=48, 98%) still reported that they would feel comfortable prescribing immersive VR as an intervention for their patient population. CONCLUSIONS: Survey findings revealed that health care providers within this VISN for VAs have heard of VR, although they may not have actively engaged in its use. Most of the providers reported that they would prescribe the use of an immersive VR intervention for their older adult patients. This key point highlights the desire to implement VR strategies for patient use by their providers. If underlying barriers can be addressed and relatively resolved, this technological intervention has the potential to create substantial breakthroughs in clinical care.

Stress of Overseas Long-Distance Care During COVID-19: Potential "CALM"ing Strategies.

"CALM"ing strategies during COVID-19 pandemic. Created with BioRender.com.

Unexpected Findings During Double-blind Discontinuation of Acetylcholinesterase Inhibitor Medications.

PURPOSE: The long-term effects of acetylcholinesterase inhibitors (AChEIs) used in the treatment of patients with various types of dementia remain unclear, largely due to challenges in the study of their discontinuation. We present several unexpected results from a discontinuation trial that might merit further investigation. METHODS: This double-blind, placebo-controlled study of the discontinuation of AChEI medications was conducted in 62 US veterans. Participants were randomized to receive continued treatment with their medication (sham-taper group) or to treatment discontinuation via tapering (real-taper group), over a period of 6 weeks. The primary end point was the patient's/family caregiver's decision to discontinue the study medication. FINDINGS: The study was underpowered to detect a significant between-group difference in the primary end point, but examination of the discontinuation process generated several unexpected results: (1) recruitment proved extremely challenging for a variety of reasons, with <5% of potentially eligible participants enrolled; (2) all 3 patients with Parkinson disease-associated dementia showed a worsening of symptoms when they discontinued their AChEI medication, but they showed improvement after they restarted it; (3) changes in symptom-scale scores varied quite broadly across participants, regardless of treatment arm; (4) unusual effects were noted in the sham-taper arm; and (5) the only significant predictor of the decision to discontinue the study medication was a worsening in the caregiver's mood. IMPLICATIONS: These findings argue for the use of caution in discontinuing AChEIs in patients with Parkinson disease-associated dementia, although there may be potential benefits of a "drug holiday." The findings also urge the consideration of distress on the part of the caregiver while making medication treatment decisions in dementia. Future research must address challenges with recruitment and symptom fluctuations.

A systematic review of loneliness and social isolation scales used in epidemics and pandemics.

The COVID-19 pandemic has heightened social isolation and loneliness. There is a lack of consensus on rating scales to measure these constructs. Our objectives were to identify commonly used loneliness and social isolation scales over the last two decades and test their user characteristics. 7928 articles were searched in PubMed/MEDLINE, CINAHL, Web of Science, and APA PsychINFO databases. 41 articles were included based on study criteria. Among fourteen scales reported, UCLA 3-item loneliness scale was found to be most commonly used. The scale is specifically developed for telephone use and is the fastest taking less than a minute for self-administration.

New onset multimodal hallucinations associated with mirtazapine: a case report.

Mirtazapine, a commonly used antidepressant, has a relatively safe side effect profile and is commonly used in the elderly for treatment of depression. It has been proposed as being particularly suitable for patients with depression associated with insomnia and weight loss. Although mental status changes and perceptual abnormalities secondary to its use are rare, special care needs to be taken, especially while starting treatment or while increasing the dose. We report three cases of auditory, musical and visual hallucinations associated with the use of mirtazapine.

Neuropsychological and Functional Impact of COVID-19 on Mild Cognitive Impairment.

We present a case report to showcase that behavioral, cognitive, and functional decline may be associated with COVID-19 stay-home guidance among older adults with pre-existent cognitive impairment. In a functionally independent and physically active older adult with Mild Cognitive Impairment, there was worsening in depression and anxiety symptoms associated with the restrictions of COVID-19. Functional decline was also noted as assessed by Instrumental Activities of Daily Living. We discuss solutions to mitigate the effects of COVID-19 restrictions in this vulnerable population.

Conducting Clinical Research During the COVID-19 Pandemic: Investigator and Participant Perspectives.

As the medical landscape changes daily with the coronavirus disease (COVID-19) pandemic, clinical researchers are caught off-guard and are forced to make decisions on research visits in their ongoing clinical trials. Although there is some guidance from local and national organizations, the principal investigator (PI) is ultimately responsible for determining the risk-benefit ratio of conducting, rescheduling, or cancelling each research visit. The PI should take into consideration the ethical principles of research, local/national guidance, the community risk of the pandemic in their locale, staffing strain, and the risk involved to each participant, to ultimately decide on the course of action. While balancing the rights and protection of the human subject, we seldom examine patients' views and opinions about their scheduled research visit(s). This article discusses the ethical principles of beneficence and autonomy in helping the decision-making process. We discuss ways to weigh-in local and national guidance, staffing strain, and institutional support into the decision-making process and outline potential changes needed for regulatory bodies depending on the decision. Further, we discuss the need to weigh-in the individual risk-benefit ratio for each participant and present a decision tree to navigate this complex process. Finally, we examine participant and caregiver perspectives on their fears, sense of preparedness, and factors that they consider before deciding whether to keep or postpone the research appointments. This entry also provides PIs ways to support their research participants in both scenarios, including provision of psychological support.

Selective serotonin reuptake inhibitors-associated apathy syndrome: A cross sectional study.

Selective serotonin reuptake inhibitors (SSRIs), commonly used to treat depression, are associated with loss of motivation, anergy, and lack of curiosity often referred collectively as apathy. However, this association has not been systematically assessed using a specific rating scale for measuring apathy syndrome. Our objective was to study the association between SSRI use and apathy syndrome.We conducted a retrospective chart review of 125 patients enrolled in an outpatient psychiatry clinic. The prevalence of apathy syndrome and its clinical significance (based on standardized assessment) were compared between patients treated and not treated with SSRIs. Apathy was assessed using the Apathy Evaluation Scale-clinician version with a score ranging 18-72 with higher score for worse apathy. A score of greater than 30 is considered clinically significant apathy.Among 119 patients, the mean apathy scores were significantly higher in those treated with SSRIs compared to those not treated with SSRIs (42.5 ±â€Š9.2 vs 31.3 ±â€Š6, P < .0001). The SSRI group also had a significantly higher percentage of patients with clinically significant apathy (92% vs 61%, P < .0001). Use of all SSRIs was associated with the presence of apathy. Apathy was seen in all mental health diagnostic categories with highest Apathy evaluation scale-clinician version scores in those with dementia.SSRI use may be associated with higher rates of apathy syndrome. Clinicians should specifically inquire about iatrogenic apathy syndrome when evaluating patients on an SSRI if there is suspicion of loss of motivation. Limitations of this study included retrospective nature of this study, and that majority of the sample was males. Prospective studies are needed to elucidate information regarding the prevalence, etiology, and treatment response for SSRI-associated apathy syndrome.

Neuromodulation for Apathy in Alzheimer's Disease: A Double-Blind, Randomized, Sham-Controlled Pilot Study.

BACKGROUND: Apathy, a profound loss of motivation, initiation, and goal directed cognition, is a common comorbidity of Alzheimer's disease (AD). The presence of apathy is associated with rapid progression of AD, long-term impairment, disability, and higher mortality. Pharmacological treatments of apathy are limited. OBJECTIVE: The primary objective was to evaluate the efficacy of repetitive transcranial magnetic stimulation (rTMS) for apathy in AD. METHODS: A randomized, double-blind, parallel-arm, sham-controlled pilot study was conducted in subjects with AD and apathy (N = 20). Subjects were randomized to rTMS or sham treatment (5 days/week) for four weeks. Primary outcome, apathy evaluation scale-clinician version (AES-C), and secondary outcome measures, modified-Mini Mental State Examination (3MS), instrumental activities of daily living (IADL), and clinical global impression (CGI), were assessed at baseline and four weeks. Follow-up visits were conducted at 8 and 12 weeks to test the durability of effects of intervention. RESULTS: Mean age was 77.3 (±7.2) years, 80% were Caucasians and 10% were females. After adjusting for baseline, there was a significantly greater improvement in the AES-C with rTMS compared to sham treatment (-10.1 (-15.9 to -4.3); t (16) â€Š= -3.69; p = 0.002) at 4 weeks. There was also significantly greater improvement in 3MS (6.9 (1.7 to 12.0); t (15) â€Š= 2.85; p = 0.012), IADL (3.4 (1.0 to 5.9); χ21 = 7.72; p = 0.006), CGI-S (1.4 (0.5 to 2.3), t (16) â€Š= 3.29; p = 0.005), and CGI-I (-2.56 (-3.5 to -1.6), t (17) â€Š= -5.72; p < 0.001) for rTMS compared to the sham at 4 weeks. The effects of rTMS were durable at 12 weeks. CONCLUSION: rTMS may be safely used in subjects with AD and may improve apathy, function, and some aspects of cognition.

An Interdisciplinary Approach to Educating Medical Students About Dementia Assessment and Treatment Planning.

BACKGROUND: Many general practitioners consider dementia care beyond their clinical domain and feel that dementia assessment and treatment should be addressed by specialists, such as geriatricians, geriatric psychiatrists, or neurologists. An urgent need exists to educate all medical trainees in dementia care, regardless of their specialization interests. OBSERVATIONS: We developed a multicomponent, experiential, brief curriculum using team-based learning to expose senior medical students who rotated through the US Department of Veterans Affairs Memory Disorders Clinic at the Central Arkansas Veterans Healthcare System in Little Rock to an interdisciplinary assessment of dementia. The curriculum included didactics, clinical experience, and team-based learning. In pre- and postevaluation, students rated their perception of the role of interdisciplinary team members in assessing and managing dementia, their personal abilities to assess cognition, behavioral problems, caregiver burden, and their perception of the impact of behavioral problems on dementia care. CONCLUSIONS: Dementia knowledge gaps were prevalent in this cohort of senior medical students. Providing interdisciplinary geriatric educational experience improved students perception of their ability to assess for dementia and their recognition of the roles of interdisciplinary team members. Plans are in place to continue and expand the program to other complex geriatric syndromes.

Participant and Caregiver Perspectives on Clinical Research During Covid-19 Pandemic.

BACKGROUND/OBJECTIVES: The COVID-19 pandemic has massively disrupted essential clinical research. Many regulatory organizations have rightfully advocated to temporarily halt enrollment and curtail all face-to-face interactions. Views and opinions of patients and their caregivers are seldom considered while making such decisions. The objective was to study older participants' and their caregivers' perspectives to participate in ongoing clinical research during the COVID-19 pandemic. DESIGN: Cross-sectional. SETTING: VISN-16/Geriatric Research, Education and Clinical Center (GRECC), Department of Veterans Affairs. PARTICIPANTS: Older participants and their caregivers (N = 51) enrolled in ongoing clinical research studies. MEASUREMENTS: Questions about perceptions of safety to attend research visit, the level of panic among the general public, and medical center's preparedness in handling the pandemic. Other questions identified the source of pandemic information and the preference of a phone or in-person visit. RESULTS: Mean age was 69.3 (±9.4) years, 53% were male, 39% were caregivers, and 65% were Caucasian. Majority (78%) of the participants felt safe/very safe attending the scheduled research appointment; 63% felt that the extra screening made them feel safe/very safe; 82% felt that the medical center was prepared/very prepared for the pandemic. Participants split evenly on their preference for phone versus in-person visits. Family members and television news media were the commonly used sources of pandemic information irrespective of their education. Perceptions were influenced by gender and source of information, not by age or education. Females perceived higher level of panic compared to males (P = .02). Those relying on news media felt safer compared to those that relied on family members (P = .008). CONCLUSION: Even though informants felt that the medical center was prepared to handle the pandemic, only half the participants preferred the in-person visit. Pandemic information was obtained from family members or the television news media. Knowing patients' perspectives may help researchers be better prepared for future pandemics. J Am Geriatr Soc 68:E14-E18, 2020.