The usability and reliability of a smartphone application for monitoring future dementia risk in ageing UK adults.

BACKGROUND: The rising number of dementia diagnoses and imminent adoption of disease-modifying treatments necessitate innovative approaches to identify individuals at risk, monitor disease course and intervene non-pharmacologically earlier in the disease course. Digital assessments of dementia risk and cognitive function have the potential to outperform traditional in-person assessments in terms of their affordability, accuracy and longitudinal tracking abilities. However, their accessibility and reliability in older adults is unclear. AIMS: To evaluate the usability and reliability of a smartphone assessment of lifestyle and cognitive factors relevant to dementia risk in a group of UK-based older adults. METHOD: Cognitively healthy adults (n = 756) recruited through the Dementias Platform UK Great Minds volunteer register completed three assessments of cognitive function and dementia risk over a 3-month period and provided usability feedback on the Five Lives smartphone application (app). We evaluated cognitive test scores for age, gender and higher education effects, normality distributions, test-retest reliability and their relationship with participants' lifestyle dementia risk factors. RESULTS: Participants found the app 'easy to use', 'quick to complete' and 'enjoyable'. The cognitive tests showed normal or near-to-normal distributions, variable test-retest reliabilities and age-related effects. Only tests of verbal ability showed gender and education effects. The cognitive tests did not correlate with lifestyle dementia risk scores. CONCLUSIONS: The Five Lives assessment demonstrates high usability and reliability among older adults. These findings highlight the potential of digital assessments in dementia research and clinical practice, enabling improved accessibility and better monitoring of cognitive health on a larger scale than traditional in-person assessments.

Barriers to brain health behaviours: results from the Five Lives Brain Health Ireland Survey.

Modifiable risk factors for dementia remain prevalent in Ireland. A detailed examination of barriers to risk reduction behaviours in an Irish context has heretofore been lacking. Many existing studies examining barriers to brain health behaviours fail to examine how they might vary across different modifiable risk factors. This study undertook a detailed assessment of barriers to individual risk reduction behaviours. As existing research suggests that barriers may vary across sociodemographic factors, we sought to investigate the distribution of barriers across age, gender, educational status, and household income. The Five Lives Brain Health Ireland Survey is a cross-sectional survey that was distributed online amongst a non-patient population. The survey captured the following: (1) Sociodemographic factors; (2) Barriers to brain health behaviours; (3) Exposure to, and knowledge of, modifiable risk factors for dementia, namely diet, social interaction, exercise, hypertension, sleep, current low mood/depression, current smoking, alcohol consumption, cognitive stimulation, hearing impairment, diabetes, air pollution, and head injury; (4) Participants' perceptions regarding potential for dementia prevention, and risk reduction. Lack of motivation was the most prevalent barrier to consuming a healthy diet (64%, n = 213), physical activity (77.7%, n = 167), smoking cessation (68%, n = 85), and moderation of alcohol intake (56.3%, n = 67). Practical factors were the most prevalent barriers to addressing low mood (56.5%, n = 87), air pollution (30.1%, n = 58), hearing impairment (63.8%, n = 44), diabetes (11.1%, n = 5), and head injury (80%, n = 8). Emotional factors were the most prevalent barriers to engaging in mentally stimulating activity (56.9%, n = 66), social activity (54.9%, n = 302), and good sleep (70.1%, n = 129). Lack of knowledge was the most prevalent barrier to hypertension control (14.4%, n = 29). Distribution of barriers varied across age, gender, educational status, and household income. This study investigated barriers to lifestyle change to improve brain health in an Irish sample of adults aged 50 and above. Detailed subtyping of barriers, as well as examination of differences according to age, gender, education, and income were undertaken. The heterogeneity of barriers to brain health behaviours revealed in this study highlights the necessity to tailor public health interventions to their target population, taking into account the gender, age, educational status, and income of recipients.

Custom-Built Operant Conditioning Setup for Calcium Imaging and Cognitive Testing in Freely Moving Mice.

Operant chambers are widely used in animal research to study cognition, motivation, and learning processes. Paired with the rapidly developing technologies for brain imaging and manipulations of brain activity, operant conditioning chambers are a powerful tool for neuroscience research. The behavioral testing and imaging setups that are commercially available are often quite costly. Here, we present a custom-built operant chamber that can be constructed in a few days by an unexperienced user with relatively inexpensive, widely available materials. The advantages of our operant setup compared with other open-source and closed-source solutions are its relatively low cost, its support of complex behavioral tasks, its user-friendly setup, and its validated functionality with video imaging of behavior and calcium imaging using the UCLA Miniscope. Using this setup, we replicate our previously published findings showing that mice exposed to social defeat stress in adolescence have inhibitory control impairments in the Go/No-Go task when they reach adulthood. We also present calcium imaging data of medial prefrontal cortex (mPFC) neuronal activity acquired during Go/No-Go testing in freely moving mice and show that neuronal population activity increases from day 1 to day 14 of the task. We propose that our operant chamber is a cheaper alternative to its commercially available counterparts and offers a better balance between versatility and user-friendly setup than other open-source alternatives.

Modifiable risk factors for dementia, and awareness of brain health behaviors: Results from the Five Lives Brain Health Ireland Survey (FLBHIS).

Up to 40% of dementias globally are attributable to modifiable risk factors. Many existing studies examining attitudes to brain health are limited by a failure to consider a range of pertinent risk factors and associated barriers to protective behaviors. In Ireland, self-reported knowledge of dementia is poor compared to other conditions. In this context, the current study aimed to explore exposure to and awareness of specific modifiable risk factors for dementia. We also aimed to investigate whether exposure to these risk factors is associated with demographic and socioeconomic factors. A cross-sectional survey was administered to 555 voluntary participants in February 2022. The survey captured the following information: (1) Sociodemographic factors; (2) Exposure to, as well as knowledge of modifiable risk factors for dementia, namely diet, social interaction, exercise, hypertension, sleep, depression, smoking, alcohol consumption, cognitive stimulation, hearing impairment, diabetes, air pollution, and head injury. The study population comprised 551 participants (50.3% male; 49.6% female). Mean age was 59.7 years. Modifiable risk factors for dementia were prevalent. Relative to females, male gender was significantly associated with multiple risk factors. Whilst 65.6% of participants believed that lifestyle improvements can decrease a person's risk of developing dementia, only 31.4% believed that dementia could be prevented. Head injury (90.9%, n = 500), low mental stimulation (85.3%, n = 469), and alcohol consumption (77.8%, n = 428) were the three most commonly recognized risk factors. Awareness was significantly greater in both university groups (undergraduate and postgraduate) for multiple risk factors. Our findings demonstrate that the distribution of exposure to modifiable risk factors for dementia is unequal across gender and age groups, and that awareness levels vary across risk factors. These findings highlight that focus surrounding dementia prevention should shift toward individual risk profiling and should be tailored toward an individual's specific needs.

Unique effects of social defeat stress in adolescent male mice on the Netrin-1/DCC pathway, prefrontal cortex dopamine and cognition (Social stress in adolescent vs. adult male mice).

For some individuals, social stress is a risk factor for psychiatric disorders characterised by adolescent onset, prefrontal cortex (PFC) dysfunction and cognitive impairments. Social stress may be particularly harmful during adolescence when dopamine (DA) axons are still growing to the PFC, rendering them sensitive to environmental influences. The guidance cue Netrin-1 and its receptor, DCC, coordinate to control mesocorticolimbic DA axon targeting and growth during this age. Here we adapted the accelerated social defeat (AcSD) paradigm to expose male mice to social stress in either adolescence or adulthood and categorised them as "resilient" or "susceptible" based on social avoidance behaviour. We examined whether stress would alter the expression of DCC and Netrin-1 in mesolimbic dopamine regions and would have enduring consequences on PFC dopamine connectivity and cognition. While in adolescence the majority of mice are resilient but exhibit risk-taking behaviour, AcSD in adulthood leads to a majority of susceptible mice without altering anxiety-like traits. In adolescent, but not adult mice, AcSD dysregulates DCC and Netrin-1 expression in mesolimbic DA regions. These molecular changes in adolescent mice are accompanied by changes in PFC DA connectivity. Following AcSD in adulthood, cognitive function remains unaffected, but all mice exposed to AcSD in adolescence show deficits in inhibitory control when they reach adulthood. These findings indicate that exposure to AcSD in adolescence vs. adulthood has substantially different effects on brain and behaviour and that stress-induced social avoidance in adolescence does not predict vulnerability to deficits in cognitive performance.Significance statement During adolescence, dopamine circuitries undergo maturational changes which may render them particularly vulnerable to social stress. While social stress can be detrimental to adolescents and adults, it may engage different mechanisms and impact different domains, depending on age. The accelerated social defeat (AcSD) model implemented here allows exposing adolescent and adult male mice to comparable social stress levels. AcSD in adulthood leads to a majority of socially avoidant mice. However, the predominance of AcSD-exposed adolescent mice does not develop social avoidance, and these resilient mice show risk-taking behaviour. Nonetheless, in adolescence only, AcSD dysregulates Netrin-1/DCC expression in mesolimbic dopamine regions, possibly disrupting mesocortical dopamine and cognition. The unique adolescent responsiveness to stress may explain increased psychopathology risk at this age.

Low-cost conditioned place preference setup including video recording and analysis of behaviour.

The conditioned place preference (CPP) paradigm is widely used in rodent research to test the rewarding and aversive properties of different stimuli. Despite its relative simplicity, commercially available CPP systems are often costly. Here we describe the construction of a CPP setup and a behavioral data analysis pipeline incorporating: • a CPP box which can be built in a single day by using widely available and affordable materials. • an open source computer system for data acquisition (based on Raspberry Pi). • a freely available behavioural analysis software. The behavioural analysis allows for measurement of both locomotor activity and time spent in a zone of interest. Including all components, our setup costs ~1/10 of the cost of the least expensive commercially available CPP boxes alone (not including data acquisition and analysis). We validated the setup by showing that a 4 mg/kg dose of amphetamine increases locomotor activity acutely in adolescent male mice and induces conditioned preference for the drug-paired compartment in the CPP test.

Distinct Populations of Neurons Activated by Heroin and Cocaine in the Striatum as Assessed by catFISH.

Despite the still prevailing notion of a shared substrate of action for all addictive drugs, there is evidence suggesting that opioid and psychostimulant drugs differ substantially in terms of their neurobiological and behavioral effects. These differences may reflect separate neural circuits engaged by the two drugs. Here we used the catFISH (cellular compartment analysis of temporal activity by fluorescence in situ hybridization) technique to investigate the degree of overlap between neurons engaged by heroin versus cocaine in adult male Sprague Dawley rats. The catFISH technique is a within-subject procedure that takes advantage of the different transcriptional time course of the immediate-early genes homer 1a and arc to determine to what extent two stimuli separated by an interval of 25 min engage the same neuronal population. We found that throughout the striatal complex the neuronal populations activated by noncontingent intravenous injections of cocaine (800 µg/kg) and heroin (100 and 200 µg/kg), administered at an interval of 25 min from each other, overlapped to a much lesser extent than in the case of two injections of cocaine (800 µg/kg), also 25 min apart. The greatest reduction in overlap between populations activated by cocaine and heroin was in the dorsomedial and dorsolateral striatum (∼30% and ∼22%, respectively, of the overlap observed for the sequence cocaine-cocaine). Our results point toward a significant separation between neuronal populations activated by heroin and cocaine in the striatal complex. We propose that our findings are a proof of concept that these two drugs are encoded differently in a brain area believed to be a common neurobiological substrate to drug abuse.