Therapeutic properties of multi-cannabinoid treatment strategies for Alzheimer’s disease

Alzheimer’s disease (AD) is a debilitating neurodegenerative disease characterized by declining cognition and behavioral impairment, and hallmarked by extracellular amyloid-β plaques, intracellular neurofibrillary tangles (NFT), oxidative stress, neuroinflammation, and neurodegeneration. There is currently no cure for AD and approved treatments do not halt or slow disease progression, highlighting the need for novel therapeutic strategies. Importantly, the endocannabinoid system (ECS) is affected in AD. Phytocannabinoids, including cannabidiol (CBD) and Δ9-tetrahydrocannabinol (THC), interact with the ECS, have anti-inflammatory, antioxidant, and neuroprotective properties, can ameliorate amyloid-β and NFT-related pathologies, and promote neurogenesis. Thus, in recent years, purified CBD and THC have been evaluated for their therapeutic potential. CBD reversed and prevented the development of cognitive deficits in AD rodent models, and low-dose THC improved cognition in aging mice. Importantly, CBD, THC, and other phytochemicals present in Cannabis sativa interact with each other in a synergistic fashion (the “entourage effect”) and have greater therapeutic potential when administered together, rather than individually. Thus, treatment of AD using a multi-cannabinoid strategy (such as whole plant cannabis extracts or particular CBD:THC combinations) may be more efficacious compared to cannabinoid isolate treatment strategies. Here, we review the current evidence for the validity of using multi-cannabinoid formulations for AD therapy. We discuss that such treatment strategies appear valid for AD therapy but further investigations, particularly clinical studies, are required to determine optimal dose and ratio of cannabinoids for superior effectiveness and limiting potential side effects. Furthermore, it is pertinent that future in vivo and clinical investigations consider sex effects

Special Libraries, February 1931

Volume 22, Issue 2https://scholarworks.sjsu.edu/sla_sl_1931/1001/thumbnail.jp

What we need as we get older : needs assessment for the development of a community geriatrics service in an Australian context

Background: The aim of this study was to inform the development of a Community Geriatrics Service (CGS) that addressed the healthcare and social needs of community dwelling older people in an Australian context. Methods: Stakeholders (N = 108) took part in a ‘needs assessment’ involving 30-min semi-structured interviews with general practitioners (GPs; N = 49), and three 2-h focus groups (community engagement meetings; N = 59) with older people, informal caregivers, allied healthcare workers, and nursing home directors. Data were transcribed and thematically coded, mapped to source and weighted to the frequency that the theme was raised across sources. Results: Five themes informing CGS development and delivery emerged: active health conditions (management of behavioural and psychological symptoms of dementia, falls, multimorbidity, and other relevant conditions), active social challenges (patient non-compliance, need for aged care social workers, caregiver stress, elder abuse, social isolation, and stigma), referrals (availability of specialists, communication, specialist input, and advance care directives), access (lack of transport options, and inaccessibility of local geriatrics clinics and specialists), and awareness (lack of awareness, knowledge, and resources). Conclusions: The CGS will need to address access, referral processes and health system navigation, which were perceived by stakeholders as significant challenges. These findings warrant the development of a CGS with an integrated approach to aged care, pertinent for the health and social needs of the elderly

Submission to the New South Wales Government's Department of Planning, Industry and Environment regarding the Design and Place State Environmental Planning Policy 2021

We are an interdisciplinary team of researchers from Western Sydney University and University of Technology Sydney, and community representatives, advocating for the recognition and inclusion of age and dementia-friendly community design principles in the Design and Place State Environmental Planning Policy (DP SEPP) 2021. Inclusive, enabling, and supportive cities are fundamental to wellbeing, especially in ageing and culturally diverse regions like South Western Sydney. Here, over 16,462 people live with dementia, and this figure will triple to 52,059 within the next 30 years unless there is a medical breakthrough1. This region is also expected to have the highest increase in dementia prevalence in all of NSW by 20501. Many of our cities in New South Wales are grappling with an ageing population and a tsunami of dementia cases with it

Neuronal correlates of cognitive control are altered in women with endometriosis and chronic pelvic pain

Endometriosis is a debilitating women's health condition and is the most common cause of chronic pelvic pain. Impaired cognitive control is common in chronic pain conditions, however, it has not yet been investigated in endometriosis. The aim of this study was to explore the neuronal correlates of cognitive control in women with endometriosis. Using a cross-sectional study design with data collected at a single time-point, event-related potentials were elicited during a cued continuous performance test from 20 women with endometriosis (mean age = 28.5 ± 5.2 years) and 20 age- and gender-matched controls (mean age = 28.5 ± 5.2 years). Event-related potential components were extracted and P3 component amplitudes were derived with temporal principal components analysis. Behavioral and ERP outcomes were compared between groups and subjective pain severity was correlated with ERP component amplitudes. No significant behavioral differences were seen in task performance between the groups (all p > 0.094). Target P3b (all p < 0.034) and SW (all p < 0.040), and non-target early P3a (eP3a; all p < 0.023) and late P3a (lP3a; all p < 0.035) amplitudes were smaller for the endometriosis compared to the healthy control group. Lower non-target eP3a (p < 0.001), lP3a (p = 0.013), and SW (p = 0.019) amplitudes were correlated with higher pain severity scores. Findings suggest that endometriosis-associated chronic pelvic pain is linked to alterations in stimulus-response processing and inhibitory control networks, but not impaired behavioral performance, due to compensatory neuroplastic changes in overlapping cognitive control and pain networks

Electrophysiological correlates of the brain-derived neurotrophic factor (BDNF) Val66Met polymorphism

The brain-derived neurotrophic factor (BDNF) protein is essential for neuronal development. Val66Met (rs6265) is a functional polymorphism at codon 66 of the BDNF gene that affects neuroplasticity and has been associated with cognition, brain structure and function. The aim of this study was to clarify the relationship between BDNF Val66Met polymorphism and neuronal oscillatory activity, using the electroencephalogram (EEG), in a normative cohort. Neurotypical (N = 92) young adults were genotyped for the BDNF Val66Met polymorphism and had eyes open resting-state EEG recorded for four minutes. Focal increases in right fronto-parietal delta, and decreases in alpha-1 and right hemispheric alpha-2 amplitudes were observed for the Met/Met genotype group compared to Val/Val and Val/Met groups. Stronger frontal topographies were demonstrated for beta-1 and beta-2 in the Val/Met group versus the Val/Val group. Findings highlight BDNF Val66Met genotypic differences in EEG spectral amplitudes, with increased cortical excitability implications for Met allele carriers

“We need a one-stop-shop” : co-creating the model of care for a multidisciplinary memory clinic with community members, GPs, aged care workers, service providers, and policy-makers

Background: Timely diagnosis of dementia has a wide range of benefits including reduced hospital emergency department presentations, admissions and inpatient length of stay, and improved quality of life for patients and their carers by facilitating access to treatments that reduce symptoms, and allow time to plan for the future. Memory clinics can provide such services, however there is no 'gold standard' model of care. This study involved the co-creation of a model of care for a new multidisciplinary memory clinic with local community members, General Practitioners (GPs), policy-makers, community aged care workers, and service providers. Methods: Data collection comprised semi-structured interviews (N=98) with 20 GPs, and three 2-h community forums involving 53 seniors and community/local government representatives, and 25 community healthcare workers. Interviews and community forums were audio-recorded, transcribed verbatim, and coded by thematic analysis using Quirkos. Results: GPs’ attitudes towards their role in assessing people with dementia varied. Many GPs reported that they found it useful for patients to have a diagnosis of dementia, but required support from secondary care to make the diagnosis and assist with subsequent management. Community forum participants felt they had a good knowledge of available dementia resources and services, but noted that these were highly fragmented and needed to be easier to navigate for the patient/carer via a 'one-stop-shop' and the provision of a dementia key worker. Expectations for the services and features of a new memory clinic included diagnostic services, rapid referrals, case management, education, legal services, culturally sensitive and appropriate services, allied health, research participation opportunities, and clear communication with GPs. Participants described several barriers to memory clinic utilisation including transportation access, funding, awareness, and costs. Conclusion: This study demonstrates the importance of working with stakeholders to co-design models of care for people with dementia that take into account the local communities’ needs. Findings pave the way for the development of a potential new “gold standard” memory clinic model of care and operationalise new national clinical guidelines

Cognitive anxiolytics

Cognitive defi cits, such as poor concentration, attention, and memory, are common features of anxiety disorders, including generalised anxiety disorder (GAD), panic disorder (PD), and social anxiety disorder (SAD). First-line pharmacological treatments for anxiety disorders, particularly benzodiazepines, may compound these cognitive defi cits due to their sedative actions. Complementary and alternative treatments with combined anxiolytic and cognitive-enhancing properties, hereto referred to as cognitive anxiolytics, would be benefi cial to the fi eld. The research outlined in this chapter details evidence on a range of herbs including Bacopa monnieri , Ginkgo biloba , Melissa offi cinalis , Camellia sinensis , Salvia spp., and Rosmarinus offi cinalis that have both cognitive-enhancing and anxiolytic properties. A range of mechanisms of action have been proposed to account for these effects including antioxidant, acetylcholinesterase (AChE) inhibition, increased cerebral blood fl ow (CBF), cholinergic enhancement (binding to both nicotinic and muscarinic receptors), and γ-aminobutyric acid (GABA) potentiation

Exploring the mechanism of dishabituation

In this study we explored elicitation and habituation of the orienting reflex (OR) in the context of indifferent and significant stimuli, particularly aiming to clarify the mechanism driving dishabituation. An in-depth analysis of the mechanisms of electrodermal habituation and dishabituation was conducted, focusing on the role of state measures as determinants of the phasic response profile. Twenty-four young adult participants completed an auditory dishabituation task while electrodermal activity was recorded. Participants listened to a series of 10 innocuous tones of the same frequency (standards), followed by a deviant tone of a different frequency, and succeeded by 2-4 tones of the same frequency as the initial 10 stimuli. All stimuli had a random stimulus onset asynchrony of 5-7 s. Participants completed an indifferent condition in which there was no task in relation to the stimuli, and a significant condition where instruction was given to count the stimuli silently; order was counterbalanced between participants. As predicted, both skin conductance responses (SCRs) and skin conductance levels (SCLs) were larger for the significant than the indifferent condition. The initial phasic ORs were dependent on pre-stimulus arousal level, and there were significant decreases in both SCR and SCL over the first 10 standards in both conditions. Phasic response recovery was apparent to the deviant stimulus, and dishabituation to the following standard stimulus; both effects were enhanced in the significant condition. Sensitisation was apparent in SCL following the initial and deviant stimuli, but the extent of this was confounded with incomplete resolution of the preceding phasic OR in the significant condition. In the indifferent condition, dishabituation was independent of deviant-related sensitisation; this could not be tested in the significant condition. These findings suggest that dishabituation is not a process of sensitisation, but rather, a disruption of the habituation process

People with dementia : the challenges for data collection with a vulnerable population

The term “dementia” covers a range of degenerative neurological conditions that lead to severe cognitive decline along with a broad spectrum of accompanying behavioral and psychological symptoms. Conventional pharmacological treatments for these symptoms and the underlying pathophysiologies are limited and can lead to undesirable side effects. There is, therefore, an increasing interest in research into the effectiveness of non-pharmacological complementary medicines, including music therapy, herbal medicine, and lifestyle modifications such as physical activity and diet. However, there are a number of challenges inherent in conducting research involving people who have dementia and their families, such as low recruitment and high attrition rates, communication difficulties, managing expectations of families, and challenges associated with the collection of physiological data. In this case, we discuss research we have conducted involving the use of music and qualitative interviews in people with mild to more severe dementia and suggest some pragmatic strategies for dealing with the difficulties we have encountered in conducting such research