Optimal deep brain stimulation sites and networks for stimulation of the fornix in Alzheimer's disease.

Deep brain stimulation (DBS) to the fornix is an investigational treatment for patients with mild Alzheimer's Disease. Outcomes from randomized clinical trials have shown that cognitive function improved in some patients but deteriorated in others. This could be explained by variance in electrode placement leading to differential engagement of neural circuits. To investigate this, we performed a post-hoc analysis on a multi-center cohort of 46 patients with DBS to the fornix (NCT00658125, NCT01608061). Using normative structural and functional connectivity data, we found that stimulation of the circuit of Papez and stria terminalis robustly associated with cognitive improvement (R = 0.53, p < 0.001). On a local level, the optimal stimulation site resided at the direct interface between these structures (R = 0.48, p < 0.001). Finally, modulating specific distributed brain networks related to memory accounted for optimal outcomes (R = 0.48, p < 0.001). Findings were robust to multiple cross-validation designs and may define an optimal network target that could refine DBS surgery and programming.

Mapping autonomic, mood and cognitive effects of hypothalamic region deep brain stimulation.

Because of its involvement in a wide variety of cardiovascular, metabolic and behavioural functions, the hypothalamus constitutes a potential target for neuromodulation in a number of treatment-refractory conditions. The precise neural substrates and circuitry subserving these responses, however, are poorly characterized to date. We sought to retrospectively explore the acute sequelae of hypothalamic region deep brain stimulation and characterize their neuroanatomical correlates. To this end we studied-at multiple international centres-58 patients (mean age: 68.5 ± 7.9 years, 26 females) suffering from mild Alzheimer's disease who underwent stimulation of the fornix region between 2007 and 2019. We catalogued the diverse spectrum of acutely induced clinical responses during electrical stimulation and interrogated their neural substrates using volume of tissue activated modelling, voxel-wise mapping, and supervised machine learning techniques. In total 627 acute clinical responses to stimulation-including tachycardia, hypertension, flushing, sweating, warmth, coldness, nausea, phosphenes, and fear-were recorded and catalogued across patients using standard descriptive methods. The most common manifestations during hypothalamic region stimulation were tachycardia (30.9%) and warmth (24.6%) followed by flushing (9.1%) and hypertension (6.9%). Voxel-wise mapping identified distinct, locally separable clusters for all sequelae that could be mapped to specific hypothalamic and extrahypothalamic grey and white matter structures. K-nearest neighbour classification further validated the clinico-anatomical correlates emphasizing the functional importance of identified neural substrates with area under the receiving operating characteristic curves between 0.67 and 0.91. Overall, we were able to localize acute effects of hypothalamic region stimulation to distinct tracts and nuclei within the hypothalamus and the wider diencephalon providing clinico-anatomical insights that may help to guide future neuromodulation work.

Design and Implementation of a Regional Inpatient Psychiatry Unit for Patients who are Positive for Asymptomatic SARS-CoV-2.

BACKGROUND: Patients with psychiatric illnesses are particularly vulnerable to highly contagious, droplet-spread organisms such as SARS-CoV-2. Patients with mental illnesses may not be able to consistently follow up behavioral prescriptions to avoid contagion, and they are frequently found in settings with close contact and inadequate infection control, such as group homes, homeless shelters, residential rehabilitation centers, and correctional facilities. Furthermore, inpatient psychiatry settings are generally designed as communal spaces, with heavy emphasis on group and milieu therapies. As such, inpatient psychiatry services are vulnerable to rampant spread of contagion. OBJECTIVE: With this in mind, the authors outline the decision process and ultimate design and implementation of a regional inpatient psychiatry unit for patients infected with asymptomatic SARS-CoV-2 and share key points for consideration in implementing future units elsewhere. CONCLUSION: A major takeaway point of the analysis is the particular expertise of trained experts in psychosomatic medicine for treating patients infected with SARS-CoV-2.

Management of behavioral and psychological symptoms in people with Alzheimer's disease: an international Delphi consensus.

ABSTRACTObjectives:Behavioral and psychological symptoms of dementia (BPSD) are nearly universal in dementia, a condition occurring in more than 40 million people worldwide. BPSD present a considerable treatment challenge for prescribers and healthcare professionals. Our purpose was to prioritize existing and emerging treatments for BPSD in Alzheimer's disease (AD) overall, as well as specifically for agitation and psychosis. DESIGN: International Delphi consensus process. Two rounds of feedback were conducted, followed by an in-person meeting to ratify the outcome of the electronic process. SETTINGS: 2015 International Psychogeriatric Association meeting. PARTICIPANTS: Expert panel comprised of 11 international members with clinical and research expertise in BPSD management. RESULTS: Consensus outcomes showed a clear preference for an escalating approach to the management of BPSD in AD commencing with the identification of underlying causes. For BPSD overall and for agitation, caregiver training, environmental adaptations, person-centered care, and tailored activities were identified as first-line approaches prior to any pharmacologic approaches. If pharmacologic strategies were needed, citalopram and analgesia were prioritized ahead of antipsychotics. In contrast, for psychosis, pharmacologic options, and in particular, risperidone, were prioritized following the assessment of underlying causes. Two tailored non-drug approaches (DICE and music therapy) were agreed upon as the most promising non-pharmacologic treatment approaches for BPSD overall and agitation, with dextromethorphan/quinidine as a promising potential pharmacologic candidate for agitation. Regarding future treatments for psychosis, the greatest priority was placed on pimavanserin. CONCLUSIONS: This international consensus panel provided clear suggestions for potential refinement of current treatment criteria and prioritization of emerging therapies.

Training in psychosomatic medicine: a psychiatric subspecialty recognized in the United States by the American board of medical specialties.

Psychosomatic Medicine (PM) is a subspecialty of Psychiatry approved by the American College of Graduate Medical Education (ACGME) in 2003. Since its approval, subspecialty training programs in PM have been created in the United States. Training programs are designed to educate trainees in the psychiatric care of the complex medically ill, and are centered around development of certain core competencies by trainees. Completion of an ACGME-accredited training program in PM allows the graduate to sit for the PM subspecialty board examination. Development of centers with academic PM programs will lead to an increase in the depth of knowledge about the care of the complex medically ill with psychiatric comorbidities, and may thus lead to improved medical outcomes for this population. There are also individual benefits to subspecialty training in PM. In addition, there are barriers to extended postgraduate training that may require systems-level interventions to overcome.

Management of agitation and aggression associated with Alzheimer disease.

Agitation and aggression are frequently occurring and distressing behavioral and psychological symptoms of dementia (BPSD). These symptoms are disturbing for individuals with Alzheimer disease, commonly confer risk to the patient and others, and present a major management challenge for clinicians. The most widely prescribed pharmacological treatments for these symptoms-atypical antipsychotics-have a modest but significant beneficial effect in the short-term treatment (over 6-12 weeks) of aggression but limited benefits in longer term therapy. Benefits are less well established for other symptoms of agitation. In addition, concerns are growing over the potential for serious adverse outcomes with these treatments, including stroke and death. A detailed consideration of other pharmacological and nonpharmacological approaches to agitation and aggression in patients with Alzheimer disease is, therefore, imperative. This article reviews the increasing evidence in support of psychological interventions or alternative therapies (such as aromatherapy) as a first-line management strategy for agitation, as well as the potential pharmacological alternatives to atypical antipsychotics-preliminary evidence for memantine, carbamazepine, and citalopram is encouraging.

Better cognitive performance in elderly taking antioxidant vitamins E and C supplements in combination with nonsteroidal anti-inflammatory drugs: the Cache County Study.

Studies have shown less cognitive decline and lower risk of Alzheimer's disease in elderly individuals consuming either antioxidant vitamins or nonsteroidal anti-inflammatory drugs (NSAIDs). The potential of added benefit from their combined use has not been studied. We therefore analyzed data from 3,376 elderly participants of the Cache County Study who were given the Modified Mini-Mental State examination up to three times during a period of 8 years. Those who used a combination of vitamins E and C supplements and NSAIDs at baseline declined by an average 0.96 fewer points every 3 years than nonusers (P < .05). This apparent effect was attributable entirely to participants with the APOE epsilon4 allele, whose users declined by 2.25 fewer points than nonusers every 3 years (P < .05). These results suggest that among elderly individuals with an APOE epsilon4 allele, there is an association between using antioxidant supplements in combination with NSAIDs and less cognitive decline over time.

Risk of mortality with vitamin E supplements: the Cache County study.

PURPOSE: A recent meta-analysis reported increased mortality in clinical trial participants randomized to high-dose vitamin E. We sought to determine whether these mortality risks with vitamin E reflect adverse consequences of its use in the presence of cardiovascular disease. METHODS: In a defined population aged 65 years or older, baseline interviews captured self- or proxy-reported history of cardiovascular illness. A medicine cabinet inventory verified nutritional supplement and medication use. Three sources identified subsequent deaths. Cox proportional hazards methods examined the association between vitamin E use and mortality. RESULTS: After adjustment for age and sex, there was no association in this population between vitamin E use and mortality (adjusted hazard ratio [aHR] 0.93; 95% confidence interval [CI], 0.74-1.15). Predictably, deaths were more frequent with a history of diabetes, stroke, coronary artery bypass graft surgery, or myocardial infarction, and with the use of warfarin, nitrates, or diuretics. None of these conditions or treatments altered the null main effect with vitamin E, but mortality was increased in vitamin E users who had a history of stroke (aHR 3.64; CI, 1.73-7.68), coronary bypass graft surgery (aHR 4.40; CI, 2.83-6.83), or myocardial infarction (aHR 1.95; CI, 1.29-2.95) and, independently, in those taking nitrates (aHR 3.95; CI, 2.04-7.65), warfarin (aHR 3.71; CI, 2.22-6.21), or diuretics (aHR 1.83; CI, 1.35-2.49). Although not definitive, a consistent trend toward reduced mortality was seen in vitamin E users without these conditions or treatments. CONCLUSIONS: In this population-based study, vitamin E use was unrelated to mortality, but this apparently null finding seems to represent a combination of increased mortality in those with severe cardiovascular disease and a possible protective effect in those without.

Psychosomatic medicine: A new psychiatric subspecialty in the U.S. focused on the interface between psychiatry and medicine

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Background and Objectives: In the past, Psychosomatic Medicine (PM) has had ambiguous connotations, and there have been many other names for this specialized fields, including Consultation-Liaison Psychiatry. The objective of this report is to briefly review the background, the history and current status of PM, which recently was recognized in the U.S. a psychiatric subspecialty. Methods: Historical review and review of the literature. Results: PM has a rich history. Psychoanalysts and psychophysiologists pioneered the study of mind-body interactions, and crucial events in the development include the funding of PM units in several U.S. teaching hospitals by the Rockefeller Foundation, and the training grants and a research development program funded by the National Institute of Mental Health. By the 1980s, all psychiatry residency programs were requiered to provide substancial clinical experience in the field, and as of 2005 there were 32 fellowship programs in the Academy of Psychosomatic Medicine's (APM) directory. In 2001, The Academy of Psychosomatic Medicine (APM) applied for the recognition of PM as a subspecialty of psychiatry, and formal approval was granted by the American Board of Medical Specialties (ABMS) in March 2003. The foundation of PM is a specialized body of scientific knowledge regarding psychiatric aspects of medical illness. This has been articulated in contemporary textbooks, journals and regular scientificic meetings of national and international societies A cadre of scholars and researchers has emerged, and important contributions have occurred. A major goal of the PM field is to improve the psychiatric care of patients with complex medical conditions. There are a number of obstacles and challenges ahead in pursuing optimal integration of PM services into existing service delivery systems of care, but anticipated expansion of accredited fellowship programs in PM will hopefully help address this shortfall. In the past 20 years an international PM network has developed with increasing scientific exchanges, and the US paradigm is regarded as important for the development of PM as a subspecialty internationally. Conclusion: Formal recognition as a subspecialty in the U.S. has and will strengthen PM and will enhance its growth internationally (AU)

Psychosomatic medicine: a new psychiatric subspecialty.

OBJECTIVE: Psychosomatic medicine, also known as consultation-liaison psychiatry, received approval as a subspecialty field of psychiatry by the American Board of Medical Specialties in the spring of 2003. This represents a crucial step in the development of the field of psychosomatic medicine and recognition by leaders in the fields of medicine and psychiatry of its importance. METHODS: The field was developed in response to evidence suggesting that a high prevalence of psychiatric disorders exists in patients with complex medical illnesses and that diagnosis and management of these disorders in this population is critical yet frequently complicated by the medical illnesses themselves. RESULTS: Psychosomatic medicine psychiatrists have developed specialized expertise in addressing these issues. CONCLUSION: The approval of subspecialty status for psychosomatic medicine will help promote the psychiatric care of patients with complex medical, surgical, obstetrical and neurological conditions, as well as foster further improvements in the quality of training and research in this important area.