This concurrent, exploratory, mixed-methods process evaluation, embedded within a randomised controlled trial, investigates how the ‘active prevention in people at risk of dementia through lifestyle behaviour change and technology to build resilience’ (APPLE-Tree) secondary dementia prevention intervention might support behavioural and lifestyle goal attainment, through determining the contexts influencing engagement and testing intervention theoretical assumptions.

We aimed to investigate (a) intervention reach, dose and fidelity, (b) contexts influencing engagement and (c) alignment of findings with theoretical assumptions about how the intervention might have supported participants to meet personalised behavioural and lifestyle goals.

We measured intervention reach and dose. We selected interviewees for setting, gender and ethnic diversity from the 374 APPLE-Tree trial participants randomised to the intervention arm. We interviewed 25 intervention participants, 12 facilitators and 3 study partners. Additionally, we analysed 11 interviews previously conducted during or after intervention delivery for an ethnography, and 233 facilitator-completed participant goal records. We thematically analysed data, combining inductive/deductive approaches informed by the ‘capability, opportunity and motivation-behaviour’ (COM-B) behaviour change model. We video-recorded a randomly selected tenth of sessions and rated fidelity.

A total of 346 of 374 (92.5%) intervention arm participants received some intervention (reach), and 305 of 374 (81.6%) attended ≥5 main sessions (predefined as adhering: dose). According to facilitator records, participants met a mean of 5.1 of 7.5 (68.3%) goals set. We generated three themes around (a) building capability and motivation, (b) connecting with other participants and facilitators and (c) flexibility and a tailored approach.

The intervention supported behaviour change, through increasing knowledge and providing space to plan, implement and evaluate new strategies and make social connections. Feedback indicated that the intervention was flexible and inclusive of diverse preferences and needs.

Cognitive impairment is a significant, yet often overlooked, non-motor symptom of Parkinson’s disease, and a strong predictor of quality of life for those affected. Despite the availability of both pharmacological and non-pharmacological treatment options for Parkinson’s disease, their efficacy for the cognitive symptoms of the disease specifically is unclear, as no ‘gold standard’ treatment strategy for cognitive impairment in the disease has yet emerged. Further, a comparative understanding of the efficacy of each of these treatment options is severely lacking.

This systematic review aims to critically evaluate the efficacy of non-pharmacological interventions for the treatment of cognitive impairment in Parkinson’s disease.

A comprehensive systematic search will be conducted to identify studies involving participants clinically diagnosed with Parkinson’s disease that assess non-pharmacological interventions targeting cognitive impairment. If feasible, results will be synthesised using meta-analysis; otherwise, narrative synthesis will be used.

This is a protocol for a systematic review that is yet to be conducted.

The findings from this review will provide critical insight into the efficacy of non-pharmacological treatment options for cognitive impairment in Parkinson’s disease, which may help to influence clinical recommendations for the treatment of cognitive impairment in Parkinson’s disease and highlight existing gaps in the literature.

White matter hyperintensities (WMH) on fluid-attenuated inversion recovery MRI sequence are regions where fluid from supplying vessels leaks into brain tissue. Some studies have demonstrated an association between WMH and cognitive decline. Given the common WMH risk factors in our local population, the aim of this study is to examine the relationship of overall and regional WMH with cognition in Hamilton, Canada.

Adults presenting to Hamilton General Hospital in 2020 with a head MRI and cognitive assessment within 6 months of the MRI were included in our cross-sectional study. MRIs were reviewed, assigning a periventricular (PV), a subcortical (SC) and an overall severity score to each based on the Fazekas scale, ranging from 0 to 3. Montreal Cognitive Assessment (MoCA) scores were used as a measure of cognitive function. Patients with confounding diagnoses were excluded. Multiple regression analyses were conducted between WMH and cognitive scores, adjusting for hypertension, diabetes and smoking.

Multiple regression models revealed R2 values of 0.097, 0.050 and 0.036 for overall, PV and SC WMH with MoCA, respectively. There were negative associations between overall Fazekas scores and MoCA (B = −2.11, p < 0.001), PV scores and MoCA (B = −1.46, p < 0.001) and SC scores and MoCA (B = −1.21, p = 0.002).

The association between MRI WMH and cognition supports prognostic use for cognitive decline to limit/delay deterioration. Specifically, stronger PV associations prompt research and perhaps development of revised scales prioritizing PV changes. Implementing this into the field of radiology whereby WMH severity and location assessment becomes a standard within brain MRI reports could improve patient outcomes.

Irisin is a glycosylated polypeptide hormone derived from muscles that plays a crucial role in learning and memory by promoting the growth of hippocampal neurons, thereby influencing cognitive function.

Despite increasing evidence, a comprehensive understanding of the exact role of irisin remains elusive, necessitating further research to unravel the complex mechanisms through which irisin influences cognitive function and to explore therapeutic approaches targeting irisin.

A literature review was performed by searching PubMed for articles published between 2012 and 2024, using the keywords ‘fibronectin type III domain-containing 5 (FNDC5)’, ‘irisin’, ‘cognitive impairment’, ‘Alzheimer’s disease’, ‘Age-related cognitive dysfunction’ and ‘Diabetes-associated cognitive dysfunction’, combined with Boolean operators (AND/OR).

This review highlighted the potential impact of irisin on cognitive function in the context of ageing, diabetes and Alzheimer’s disease. The anti-cognitive impairment effects of irisin are associated with the regulation of energy metabolism, insulin resistance, inflammation, oxidative stress, amyloid-beta deposition, synaptogenesis and plasticity. The signalling pathways through which irisin improves cognitive impairment are complex and highly regulated processes, involving multiple signalling pathways such as the adenosine monophosphate-activated protein kinase (AMPK) signalling pathway, mitogen-activated protein kinase (MAPK) signalling pathway, nuclear factor-κB (NF-κB) signalling pathway, ERK-STAT3 signalling pathway, cAMP/PKA/CREB signalling pathway and Nrf2/HO-1 signalling pathway.

This review delves into the positive effects of irisin on cognitive impairment, examines the signalling pathways related to fibronectin type III domain-containing 5 (FNDC5)/irisin and provides future perspectives for research on the anti-cognitive impairment effects of irisin.

The cognitive trajectory of aging individuals with childhood-onset epilepsy is poorly understood. Our aim was to examine cognitive change over a 7-year period in aging individuals with epilepsy, originally recruited for prospective follow up in the early 1960’s.

36 participants with childhood-onset epilepsy from a prospective population-based cohort and 39 controls participated in the 50-year and 57-year follow-up data collections. Eight participants had active epilepsy, 28 were in remission. Eleven neuropsychological tests were used to measure language/semantic function, episodic memory and learning, executive function, visuomotor function, and working memory. Regression-based standardized change scores were used to control for sources of error in test-retest assessments.

Participants with epilepsy lacked a test-retest effect in language functions. A significant decline was found in participants with active epilepsy in episodic memory functions overall, and in those with remitted epilepsy in learning, immediate recall and set-shifting. The risk of clinically significant general cognitive decline was higher in participants with active epilepsy (OR 61.25, 95% CI 5.92–633.81, p = .0006). Among those with remitted epilepsy the risk was lower and non-significant (OR 2.19, 95% CI 0.58–8.23, p = .24).

Our results demonstrate poorer cognitive trajectories in participants with childhood-onset epilepsy compared to controls, particularly in those with active epilepsy. The risk of general cognitive decline was lower in participants with remitted epilepsy, but a decline in episodic memory functions was observed. Our findings likely reflect faster brain aging in childhood-onset epilepsy, even in individuals with early remission.

Assessment of regional glucose metabolism by [18F]fluorodeoxyglucose position emission tomography ([18F]FDG PET) serves as a biomarker for differential diagnosis of dementia. Conversely, depressive cognitive impairment shows no abnormalities on cerebral [18F]FDG PET.

This study validates the diagnostic value of [18F]FDG PET in addition to clinical diagnosis in a real-life gerontopsychiatric clinical population.

Ninety-eight consecutive patients with depression and cognitive impairment were included. Baseline clinical diagnoses were independently established before and after disclosure of [18F]FDG PET, and dichotomised into neurodegenerative or non-neurodegenerative diseases (level 1). Subsequently, neurodegenerative cases were allocated to diagnostic subgroups (Alzheimer’s disease, Lewy body diseases, frontotemporal lobar degeneration, neurodegenerative other; level 2). An interdisciplinary, biomarker-supported consensus diagnosis after a median follow-up of 6.6 month after [18F]FDG PET served as reference. Changes of clinical diagnoses and diagnostic accuracy were assessed.

After disclosure of [18F]FDG PET, level-1 clinical diagnoses changed in 23% (95% CI 16–33%) of cases, improving the diagnostic accuracy from 72% (95% CI 62–81%) to 92% (95% CI 84–96%) (P < 0.001). [18F]FDG PET was of particular value for exclusion of neurodegenerative disease. Concerning level-2 decisions, the clinical diagnoses changed in 30% (95% CI 21–40%) of cases, increasing its accuracy from 64% (95% CI 54–74%) to 85% (95% CI 76–91%) (P < 0.001). A major fraction of incorrect level-2 diagnoses comprised Alzheimer’s disease misdiagnosed as Lewy body diseases.

[18F]FDG PET provides a significant incremental diagnostic value beyond the clinical diagnosis in depressive cognitive impairment. Thus, [18F]FDG PET should be considered in the diagnostic work-up of patients with mental disorders and cognitive impairment.

The relationship between emotional symptoms and cognitive impairments in major depressive disorder (MDD) is key to understanding cognitive dysfunction and optimizing recovery strategies. This study investigates the relationship between subjective and objective cognitive functions and emotional symptoms in MDD and evaluates their contributions to social functioning recovery.

The Prospective Cohort Study of Depression in China (PROUD) involved 1,376 MDD patients, who underwent 8 weeks of antidepressant monotherapy with assessments at baseline, week 8, and week 52. Measures included the Hamilton Depression Rating Scale (HAMD-17), Quick Inventory of Depressive Symptomatology-Self Report (QIDS-SR16), Chinese Brief Cognitive Test (C-BCT), Perceived Deficits Questionnaire for Depression-5 (PDQ-D5), and Sheehan Disability Scale (SDS). Cross-lagged panel modeling (CLPM) was used to analyze temporal relationships.

Depressive symptoms and cognitive measures demonstrated significant improvement over 8 weeks (p < 0.001). Baseline subjective cognitive dysfunction predicted depressive symptoms at week 8 (HAMD-17: β = 0.190, 95% CI: 0.108–0.271; QIDS-SR16: β = 0.217, 95% CI: 0.126–0.308). Meanwhile, baseline depressive symptoms (QIDS-SR16) also predicted subsequent subjective cognitive dysfunction (β = 0.090, 95% CI: 0.003-0.177). Recovery of social functioning was driven by improvements in depressive symptoms (β = 0.384, p < 0.0001) and subjective cognition (β = 0.551, p < 0.0001), with subjective cognition contributing more substantially (R2 = 0.196 vs. 0.075).

Subjective cognitive dysfunction is more strongly associated with depressive symptoms and plays a significant role in social functioning recovery, highlighting the need for targeted interventions addressing subjective cognitive deficits in MDD.

The study examines the behavioural and psychological symptoms (BPSs) associated with dementia and mild cognitive impairment (MCI), highlighting the prevalence and impact of these symptoms on individuals with varying levels of cognitive function, particularly in the context of the increasing incidence of dementia among the ageing population.

To explore the BPSs among out-patients with different cognitive statuses.

This cross-sectional study enrolled out-patients who attended the cognitive assessment out-patient clinic at our hospital between January 2018 and October 2022. The patients’ cognitive status was evaluated using the Neuropsychiatric Inventory (NPI), Activities of Daily Living and the Montreal Cognitive Assessment-Basic scales.

The study enrolled 3273 out-patients, including 688 (21%) with cognitively unimpairment, 1831 (56%) with MCI and 754 (23%) with dementia. The NPI score, the percentage of patients with BPSs and the number of BPSs increased with decreasing cognition level. Unordered logistic regression analysis showed that after adjustment of confounding variables, delusions, depression, euphoria and psychomotor alterations were independently associated with MCI. Delusions, agitation, euphoria, apathy, psychomotor alterations and sleep change were independently associated with dementia.

NPI scores, the percentage of patients with BPSs and the numbers of BPSs increased with declining cognitive function.

We sought to compare whether quality of life (QOL) in patients with subjective cognitive impairment (SCI) who performed normally on a neuropsychological battery significantly differed from those diagnosed with mild cognitive impairment (MCI), Alzheimer’s disease (AD) or non-Alzheimer’s dementia (non-AD) at initial assessment in a Rural and Remote Memory Clinic (RRMC).

610 patients referred to our RRMC between 2004 and 2019 were included in this study. We compared self-reported and caregiver-reported patient QOL scores in those with SCI (n = 166) to those diagnosed with MCI (n = 98), AD (n = 228) and non-AD (n = 118).

Patients with SCI self-reported significantly lower QOL compared to patients with AD. Interestingly, the reverse was seen in caregivers: SCI caregivers rated patient QOL higher than AD caregivers. Patients with SCI also reported lower QOL than patients with MCI. SCI caregivers reported higher patient QOL than their non-AD counterparts. Caregiver-rated patient QOL was higher in those with MCI compared to AD. Patients with MCI self-reported higher QOL scores compared to patients with non-AD dementias. Similarly, MCI caregivers reported higher patient QOL than non-AD caregivers. No other comparisons were statistically significant.

Although they lacked clinically significant cognitive deficits, patients with SCI self-reported significantly lower QOL than patients with MCI and AD. Conversely, caregiver-reported patient QOL was higher for patients with SCI than for patients with AD and non-AD. This shows that SCI seriously impacts QOL. More research is needed on how we can better support patients with SCI to improve their QOL.

Cognitive function plays a pivotal role in assessing an individual’s quality of life. This research aimed to investigate how azelaic acid (AzA), a natural dicarboxylic acid with antioxidant and anti-inflammatory properties, affects aluminium chloride (AlCl3)-induced behavioural changes and biochemical alterations in the hippocampus of rats.

Thirty-two male Wistar rats divided into four groups received distilled water, AzA 50 mg/kg, AlCl3 100 mg/kg and AzA plus AlCl3, respectively, by oral gavage for 6 weeks. Behavioural changes were evaluated using open-field maze, elevated plus maze, novel object recognition (NOR), passive avoidance task, and Morris water maze (MWM) tests. Also, malondialdehyde (MDA), carbonyl protein, tumour necrosis factor-alpha (TNF-α), interleukin-1 beta (IL-1β), nuclear factor-kappa B (NF-κB), C/EBP homologous protein (CHOP), glycogen synthase kinase-3 beta (GSK-3β), brain-derived neurotrophic factor (BDNF) and acetylcholinesterase (AChE) activity were examined.

AzA significantly affected AlCl3-provoked anxiety-like behaviours and learning and memory impairments. It also reduced the toxic effect of AlCl3 on MDA, carbonyl protein, TNF-α, IL-1β, NF-κB and GSK-3β status; however, its beneficial effects on AlCl3-induced changes of CHOP, BDNF and AChE activity were not significant.

These findings disclosed that AzA could improve behavioural and cognitive function and almost limit the oxidative stress and neuroinflammation caused by AlCl3.

Validated computerized assessments for cognitive functioning are crucial for older individuals and those at risk of cognitive decline. The National Institutes of Health (NIH) Toolbox Cognition Battery (NIHTB-CB) exhibits good construct validity but requires validation in diverse populations and for adults aged 85+. This study uses data from the Assessing Reliable Measurement in Alzheimer’s Disease and cognitive Aging study to explore differences in the factor structure of the NIHTB-CB for adults 85 and older, Black participants versus White participants, and those diagnosed as amnestic Mild Cognitive Impairment (aMCI) vs cognitively normal (CN).

Subtests from the NACC UDS-3 and NIHTB-CB were administered to 503 community-dwelling Black and White adults ages 55–99 (367 CN; 136 aMCI). Confirmatory factor analyses were used to investigate the original factor structure of NIHTB-CB that forms the basis for NIHTB-CD Index factor scores.

Factor analyses for all participants and some participant subsets (aMCI, White, 85+) substantiated the two anticipated factors (Fluid and Crystallized). However, while Black aMCI participants had the expected two-factor structure, for Black CN participants, the List Sorting Working Memory and Picture Sequence tests loaded on the Crystallized factor.

Findings provide psychometric support for the NIHTB-CB. Differences in factor structure between Black CN individuals and Black aMCI individuals suggest potential instability across levels of cognitive impairment. Future research should explore changes in NIHTB-CB across diagnoses in different populations.

Cognitive impairment, a major determinant of poor functioning in schizophrenia, had limited responses to existing antipsychotic drugs. The limited efficacy could be due to regional differences in the dysregulation of the dopamine system. This study investigated striatal and peripheral dopaminergic makers in schizophrenia and their relationship with cognitive impairment.

Thirty-three patients with schizophrenia and 36 age- and sex-matched healthy controls (HC) participated. We evaluated their cognitive performance, examined the availability of striatal dopamine transporter (DAT) using single-photon emission computed tomography with 99mTc-TRODAT, and measured plasma levels of dopaminergic precursors (phenylalanine and tyrosine) and three branched-chain amino acids (BCAA) that compete with precursors for brain uptake via ultra-performance liquid chromatography.

Schizophrenia patients exhibited lower cognitive performance, decreased striatal DAT availability, and reduced levels of phenylalanine, tyrosine, leucine, and isoleucine, and the ratio of phenylalanine plus tyrosine to BCAA. Within the patient group, lower DAT availability in the left caudate nucleus (CN) or putamen was positively associated with attention deficits. Meanwhile, lower tyrosine levels and the ratio of phenylalanine plus tyrosine to BCAA were positively related to executive dysfunction. Among all participants, DAT availability in the right CN or putamen was positively related to memory function, and plasma phenylalanine level was positively associated with executive function.

This study supports the role of dopamine system abnormalities in cognitive impairment in schizophrenia. The distinct associations between different dopaminergic alterations and specific cognitive domain impairments suggest the potential need for multifaceted treatment approaches to target these impairments.