Pairing Neutral Cues with Alcohol Intoxication: New Findings in Executive and Attention Networks

Rationale: Alcohol-associated stimuli capture attention, yet drinkers differ in the precise stimuli that become paired with intoxication. Objectives: Extending our prior work to examine the influence of alcoholism risk factors, we paired abstract visual stimuli with intravenous alcohol delivered covertly and examined brain responses to these Pavlovian conditioned stimuli in fMRI when subjects were not intoxicated. Methods: Sixty healthy drinkers performed task-irrelevant alcohol conditioning that presented geometric shapes as conditioned stimuli. Shapes were paired with a rapidly rising alcohol limb (CS+) using intravenous alcohol infusion targeting a final peak breath alcohol concentration of 0.045 g/dL or saline (CS−) infusion at matched rates. On day two, subjects performed monetary delay discounting outside the scanner to assess delay tolerance and then underwent event-related fMRI while performing the same task with CS+, CS−, and an irrelevant symbol. Results: CS+ elicited stronger activation than CS− in frontoparietal executive/attention and orbitofrontal reward-associated networks. Risk factors including family history, recent drinking, sex, and age of drinking onset did not relate to the [CS+ > CS−] activation. Delay-tolerant choice and [CS+ > CS−] activation in right inferior parietal cortex were positively related. Conclusions: Networks governing executive attention and reward showed enhanced responses to stimuli experimentally paired with intoxication, with the right parietal cortex implicated in both alcohol cue pairing and intertemporal choice. While different from our previous study results in 14 men, we believe this paradigm in a large sample of male and female drinkers offers novel insights into Pavlovian processes less affected by idiosyncratic drug associations

An Australian aged care home for people subject to homelessness: health, wellbeing and cost–benefit

Background: Older people subject to homelessness face many challenges including poor health status, geriatric syndromes, and depression, coupled with barriers in accessing health and aged care services. Many are in need of formal aged care at a younger age than the general population, yet, in Australia, specialised aged-care services to support this vulnerable cohort are limited. Methods: This study was an evaluation of a new purpose-built aged care home for people with high care needs and who are homeless or at risk of homelessness. Over the first 12 months post-admission, the study examined: (1) changes in residents’ physical, mental, psychological and social health, and (2) the costs incurred by the study cohort, including any cost benefit derived. Results: Thirty-five residents enrolled in the study between March 2020 – April 2021. At admission, almost half of residents were within the range for dementia, the majority were frail, at high risk for falls, and had scores indicative of depression. Over time, linear mixed-effect models showed significant improvement in personal wellbeing scores, with clinically significant improvements in overall health related quality of life. Levels of physical functional independence, frailty, and global cognition were stable, but cognitive functional ability declined over time. Comparison of 12 month pre- and post- admission cost utility data for a smaller cohort (n = 13) for whom complete data were available, suggested an average per resident saving of approximately AU$32,000, while the QALY indicators remained stable post-admission. Conclusion: While this was a small study with no control group, these preliminary positive outcomes add to the growing body of evidence that supports the need for dedicated services to support older people subject to homelessness

A randomized controlled trial of a decision aid for women considering genetic testing for breast and ovarian cancer risk

PURPOSE: To measure the effectiveness of a tailored decision aid (DA) designed to help women make informed decisions about genetic testing for breast/ovarian cancer risk. METHODS: A total of 145 women were randomized to receive the DA or a control pamphlet at the end of their first genetic counseling consultation. Of these, 120 (82.8%) completed two questionnaires, 1 week and 6 months post-consultation. RESULTS: While the DA had no effect on informed choice, post-decisional regret or actual genetic testing decision, the trial showed that women who received the DA had higher knowledge levels and felt more informed about genetic testing than women who received the control pamphlet (chi(2)(2) = 6.82; P = 0.033; chi(2)(1) = 4.86; P = 0.028 respectively). The DA also helped women who did not have blood drawn at their first consultation to clarify their values with regards to genetic testing (chi(2)(1) = 5.27; P = 0.022). Women who received the DA were less likely to share the information with other family members than women in the control condition (chi(2)(1) = 8.78; P = 0.003). CONCLUSIONS: Decision aids are an effective decision-support strategy for women considering genetic testing for breast/ovarian cancer risk, and are most effective before the patient has made a decision, which is generally at the point of having blood drawn

The tailored activity program (TAP) to address behavioral disturbances in frontotemporal dementia: a feasibility and pilot study

Purpose: To explore the feasibility of implementing the Tailored Activity Program with a cohort of people with frontotemporal dementia and their carers (dyads). Methods: The Tailored Activity Program is an occupational therapy based intervention that involves working collaboratively with family carers and prescribes personalized activities for behavioral management in people with dementia. Twenty dyads randomized into the study (Tailored Activity Program: n = 9; Control: n = 11) were assessed at baseline and 4-months. Qualitative analyzes evaluated feasibility and acceptability of the program for the frontotemporal dementia cohort, and quantitative analyzes (linear mixed model analyzes, Spearman’s rho correlations) measured the impact of the program on the dyads. Results: The Tailored Activity Program was an acceptable intervention for the frontotemporal dementia dyads. Qualitative analyses identified five themes: “carer perceived benefits”, “carer readiness to change”, “strategies used by carer to engage person with dementia”, “barriers to the Tailored Activity Program uptake/implementation”, and “person with dementia engagement”. Quantitative outcomes showed an overall reduction of behavioral symptoms (F 18.34 = 8.073, p = 0.011) and maintenance of functional performance in the person with dementia (F 18.03 = 0.375, p = 0.548). Conclusions: This study demonstrates the potential for using an activity-based intervention such as the Tailored Activity Program in frontotemporal dementia. Service providers should recognize that while people with frontotemporal dementia present with challenging issues, tailored therapies may support their function and reduce their behavioral symptoms.Implications for rehabilitation The Tailored Activity Program is an occupational therapy based intervention that involves prescribing personalized activities for behavioral management in dementia. The Tailored Activity Program is an acceptable and feasible intervention approach to address some of the unique behavioral and functional impairments inherent in frontotemporal dementia

Enhancing caregivers’ understanding of dementia and tailoring activities in frontotemporal dementia:two case studies

PURPOSE: To describe the intervention process and results of the Tailored Activities Program (TAP) in two people diagnosed with Frontotemporal Dementia (FTD). METHOD: TAP is an occupational therapy (OT) community-based intervention program that prescribes personalised activities to reduce difficult behaviours of dementia. The OT works with carers over a 4-month period (assessment, activity prescription, and generalisation of strategies). Study measures were collected (blind researcher) pre- and post- intervention: cognition, functional disability, behavioural symptoms, and Caregiver Confidence and Vigilance. RESULTS: A 51-year-old woman with behavioural-variant FTD could consistently engage in more activities post-intervention, with scores indicating improvements to behaviour, function, and caregiver confidence. A 63-year-old man with semantic variant FTD engaged well in the prescribed activities, with scores reflecting reduced carer distress regarding challenging behaviours and improved caregiver vigilance. CONCLUSIONS: TAP is efficacious in FTD, allowing for differences in approach for FTD subtype, where behavioural symptoms are very severe and pervasive

Apathy and functional disability in behavioral variant frontotemporal dementia

Background Behavioral variant frontotemporal dementia (bvFTD) has profound consequences on patients and their families. In this multicenter study, we investigated the contribution of cognitive and neuropsychiatric factors to everyday function at different levels of overall functional impairment. Methods In a retrospective cross-sectional study, 109 patients with bvFTD from 4 specialist frontotemporal dementia centers (Australia, England, India, and Brazil) were included. The measures administered evaluated everyday function (Disability Assessment for Dementia [DAD]), dementia staging (Clinical Dementia Rating [CDR]), general cognition (Addenbrooke’s Cognitive Examination–revised [ACE-R]), and neuropsychiatric symptoms (Neuropsychiatric Inventory [NPI]). Patients were then subdivided according to functional impairment on the DAD into mild, moderate, severe, and very severe subgroups. Three separate multiple linear regression analyses were run, where (1) total DAD, (2) basic activities of daily living (BADL), and (3) instrumental activities of daily living (IADL) scores were dependent variables; ACE-R total score and selected NPI domains (agitation/aggression, euphoria, apathy, disinhibition, irritability, aberrant motor behavior) were used as independent variables. Age, sex, education, and country of origin were controlled for in the analyses. Results Cognitive deficits were similar across the mild, moderate, and severe subgroups but significantly worse in the very severe subgroup. NPI domain scores (agitation/aggression, euphoria, apathy, disinhibition, irritability, aberrant motor behavior) did not differ across the DAD subgroups. In the multiple regression analyses, a model including ACE-R and NPI apathy explained 32.5% of the variance for total DAD scores. For IADL, 35.6% of the variance was explained by the ACE-R only. No model emerged for BADL scores. Conclusions Cognitive deficits and apathy are key contributors to functional disability in bvFTD but factors underlying impairment in BADLs remain unclear. Treatments targeting reduction of disability need to address apathy and cognitive impairment to ensure greater efficacy, especially in regards to IADLs

Rehabilitation services for young-onset dementia: examples from high- and low–middle-income countries

The WHO Dementia Global Action Plan states that rehabilitation services for dementia are required to promote health, reduce disability, and maintain quality of life for those living with dementia. Current services, however, are scarce, particularly for people with young-onset dementia (YOD). This article, written by an international group of multidisciplinary dementia specialists, offers a three-part overview to promote the development of rehabilitation services for YOD. Firstly, we provide a synthesis of knowledge on current evidence-based rehabilitative therapies for early-onset Alzheimer’s disease (EOAD), behavioural variant frontotemporal dementia (bvFTD), primary progressive aphasia (PPA), and posterior cortical atrophy (PCA). Secondly, we discuss the characteristics of rehabilitation services for YOD, providing examples across three continents for how these services can be embedded in existing settings and the different roles of the rehabilitation multidisciplinary team. Lastly, we conclude by highlighting the potential of telehealth in making rehabilitation services more accessible for people with YOD. Overall, with this paper, we aim to encourage clinical leads to begin introducing at least some rehabilitation into their services, leveraging existing resources and finding support in the collective expertise of the broader multidisciplinary dementia professional community

Benefits for children with suspected cancer from routine whole-genome sequencing

Clinical whole-genome sequencing (WGS) has been shown to deliver potential benefits to children with cancer and to alter treatment in high-risk patient groups. It remains unknown whether offering WGS to every child with suspected cancer can change patient management. We collected WGS variant calls and clinical and diagnostic information from 281 children (282 tumors) across two English units (n = 152 from a hematology center, n = 130 from a solid tumor center) where WGS had become a routine test. Our key finding was that variants uniquely attributable to WGS changed the management in ~7% (20 out of 282) of cases while providing additional disease-relevant findings, beyond standard-of-care molecular tests, in 108 instances for 83 (29%) cases. Furthermore, WGS faithfully reproduced every standard-of-care molecular test (n = 738) and revealed several previously unknown genomic features of childhood tumors. We show that WGS can be delivered as part of routine clinical care to children with suspected cancer and can change clinical management by delivering unexpected genomic insights. Our experience portrays WGS as a clinically impactful assay for routine practice, providing opportunities for assay consolidation and for delivery of molecularly informed patient care.</p