How are early-career dementia researchers considered and supported on a national level by dementia plans and organizations? An overview of global policy approaches.

INTRODUCTION: Despite representing an essential workforce, it is unclear how global policy efforts target early-career dementia researchers (ECDRs). Thus, this study aimed to provide an overview of policies through which ECDRs are considered and supported by dementia plans and organizations. METHODS: G20 member states were evaluated for their national dementia plan alongside policies of leading dementia organizations. Data targeting support for ECDRs were extracted and subject to content analysis using inductive coding. Findings were categorized and narratively synthesized. RESULTS: Only China, Denmark, England, Greece, Northern Ireland, Scotland, Spain, and the United States mentioned ECDRs in their national plan. Additionally, 17 countries formalized ECDR support via dementia organizations. Support efforts included research funding, dissemination and networking, career development, and research advice. DISCUSSION: Few nations formally recognized ECDRs in dementia plans or through dementia organizations. To facilitate equal prospects for ECDRs, top-down approaches are urged to enhance and align their efforts. HIGHLIGHTS: Few G20 countries (8/46) had national dementia plans for early-career researchers. Targeted support comes from government and nongovernmental dementia organizations. Support includes funding, training, advice, research dissemination, and networking. Inconsistent definitions and eligibility criteria are barriers to accessing support. Global coordination and top-down policy will aid early-career dementia researchers.

A systematic review of the challenges, emerging solutions and applications, and future directions of PET/MRI in Parkinson's disease.

PET/MRI is a hybrid imaging modality that boasts the simultaneous acquisition of high-resolution anatomical data and metabolic information. Having these exceptional capabilities, it is often implicated in clinical research for diagnosing and grading, as well as tracking disease progression and response to interventions. Despite this, its low level of clinical widespread use is questioned. This is especially the case with Parkinson's disease (PD), the fastest progressively disabling and neurodegenerative cause of death. To optimise the clinical applicability of PET/MRI for diagnosing, differentiating, and tracking PD progression, the emerging novel uses, and current challenges must be identified. This systematic review aimed to present the specific challenges of PET/MRI use in PD. Further, this review aimed to highlight the possible resolution of these challenges, the emerging applications and future direction of PET/MRI use in PD. EBSCOHost (indexing CINAHL Plus, PsycINFO) Ovid (Medline, EMBASE) PubMed, Web of Science, and Scopus from 2006 (the year of first integrated PET/MRI hybrid system) to 30 September 2022 were used to search for relevant primary articles. A total of 933 studies were retrieved and following the screening procedure, 18 peer-reviewed articles were included in this review. This present study is of great clinical relevance and significance, as it informs the reasoning behind hindered widespread clinical use of PET/MRI for PD. Despite this, the emerging applications of image reconstruction developed by PET/MRI research data to the use of fully automated systems show promising and desirable utility. Furthermore, many of the current challenges and limitations can be resolved by using much larger-sampled and longitudinal studies. Meanwhile, the development of new fast-binding tracers that have specific affinity to PD pathological processes is warranted.

Brain function effects of exercise interventions for cognitive decline: a systematic review and meta-analysis.

Introduction: Exercise is recognized as a modifiable lifestyle factor that can mitigate cognitive decline and dementia risk. While the benefits of exercise on cognitive aging have been reported on extensively, neuronal effects in adults experiencing cognitive decline have not been systematically synthesized. The aim of this systematic review was to assess the effects of exercise on cognition and brain function in people with cognitive decline associated with dementia risk. Method: A systematic search was conducted for randomized controlled trials of ≥ 4 weeks exercise (aerobic, resistance, or mind-body) that assessed cognition and brain function using neuroimaging and neurophysiological measures in people with subjective or objective cognitive decline. Study characteristics and brain function effects were narratively synthesized, while domain-specific cognitive performance was subjected to meta-analysis. Study quality was also assessed. Results: 5,204 records were identified and 12 unique trials met the eligibility criteria, representing 646 adults classified with cognitive frailty, mild or vascular cognitive impairment. Most interventions involved 40-minute sessions conducted 3 times/week. Exercise improved global cognition (g = -0.417, 95% CI, -0.694 to -0.140, p = 0.003, I2 = 43.56%), executive function (g = -0.391, 95% CI, -0.651 to -0.131, p = 0.003, I2 = 13.28%), but not processing speed or general short-term memory (both p >0.05). Across fMRI and ERP studies, significant neuronal adaptations were found with exercise cf. control throughout the brain and were linked with improved global cognition, memory, and executive function. Cerebral blood flow was also found to improve with 24 weeks of exercise, but was not linked with cognitive changes. Discussion: The cognitive improvements associated with exercise are likely driven by increased metabolic activity, cerebrovascular mechanisms, and neuroplasticity throughout the brain. Our paper shows the promise in, and need for, high-quality trials integrating cognitive and brain function measures to elucidate the functional relationship between exercise and brain health in populations with a high risk of dementia. Systematic review registration: PROSPERO, identifier: CRD42022291843.

Study protocol for a phase III randomised controlled trial of Sailuotong (SLT) for vascular dementia and Alzheimer's disease with cerebrovascular disease.

Vascular dementia (VaD) accounts for 15-20% of all dementia cases. It is a syndrome of acquired cognitive impairment with a complex pathophysiological basis. A novel herbal formulation (Sailuotong; SLT) consisting of Panax ginseng C.A Mey, Ginkgo biloba L and Crocus sativus L extracts was developed to treat VaD. Preclinical animal studies found significant improvements in memory and in pathogenic biochemical parameters. Appropriate safety of SLT was shown in acute and chronic toxicity studies, and early clinical trials of SLT demonstrated enhancements in cognition in VaD patients. A fully powered study with a long intervention period is needed to confirm the efficacy and safety of this novel intervention. A rigorous phase III clinical trial was developed with the aim of recruiting 238 patients diagnosed with mild to moderate probable VaD, or VaD mixed with Alzheimer's disease (where cerebrovascular disease is the clinical dominant contributor to dementia, abbreviated as CVD+AD). Using a permuted block strategy, participants will be randomly allocated to receive SLT (120 mg bd) or placebo capsules for an intervention period of 52 weeks and will be followed-up for an additional 13 weeks. The primary outcome measures are the Vascular Dementia Assessment Scale-cognitive subscale and Alzheimer's Disease Cooperative Study-Activities of Daily Living scale. Secondary outcome measures include the Clinician's Interview Based Impression of Change-Plus, CLOX, EXIT-25, Neuropsychiatric Inventory-Clinician rating scale, and Dementia Quality of Life questionnaire. Safety is assessed through adverse event reports and liver, renal, and coagulation studies. Primary and secondary outcome measures will be compared between treatment and placebo groups, using intention to treat and per protocol analyses. We hypothesise that a 52-week treatment of SLT will be clinically effective and well tolerated in participants with VaD or AD+CVD. This project will provide vital efficacy and safety data for this novel treatment approach to VaD.

Computerized cognitive training in Parkinson's disease: A systematic review and meta-analysis.

Cognitive impairment is a central non-motor symptom of Parkinson's disease (PD), and there are no established treatments. Computerized cognitive training (CCT) is a safe and efficacious strategy but its efficacy in PD is unclear. We aimed to investigate the efficacy of CCT on cognitive, psychosocial and daily function, and assess potential effect moderators in people with PD without dementia. Randomized controlled trials of CCT were included in multivariate meta-analyses and meta-regressions. Seventeen studies (16 trials) encompassing 679 participants were included. The pooled effect of CCT relative to control was small and statistically significant for overall cognitive function (g=0.16; 95% CI 0.02-0.29). There was robust evidence for benefit on clinical measures of global cognition across 10 trials (g=0.33; 95% CI 0.19-0.48), especially in PD with mild cognitive impairment (PD-MCI), as well as on individual cognitive domains. Greater CCT dose and PD-MCI population were associated with larger effect sizes, but no statistically significant differences were found between subgroups. There was no significant difference in the efficacy of home-based compared to supervised training. Our findings suggest that CCT is associated with cognitive benefits in PD, including when delivered remotely. Larger, well-powered trials are warranted to examine what specific CCT regimens are most likely to promote cognitive and everyday functioning in the long-term.

Association between lifetime depression history, hippocampal volume and memory in non-amnestic mild cognitive impairment.

Hippocampal subfield volume loss in older adults with amnestic mild cognitive impairment (aMCI) and depression history are associated with amyloid beta and tau pathology, thereby increasing the risk for Alzheimer's disease (AD). However, no studies have exclusively examined distinct alterations in hippocampal subfields in non-amnestic MCI (naMCI) in relation to depression history. Here, we used both longitudinal and transverse hippocampal segmentation methods using the automated FreeSurfer software to examine whether a lifetime depression history is associated with differences in hippocampal head/body/tail (H/B/T) and key subfield volumes (CA1, subiculum, dentate gyrus) in older adults with naMCI. Further, we explored whether differences in hippocampal H/B/T and subfield volumes were associated with structured and unstructured verbal encoding and retention, comparing those with and without a depression history. The naMCI with a depression history group demonstrated larger or relatively preserved right CA1 volumes, which were associated with better unstructured verbal encoding and as well as structured verbal memory retention. This association between memory encoding and hippocampal CA1 and total head volume was significantly different to those with no depression history. The relationship between right CA1 volume and memory retention was also moderated by depression history status F (5,143) = 7.84, p < 0.001, R2  = 0.22. Those participants taking antidepressants had significantly larger hippocampal subiculum (p = 0.008), and right hippocampal body (p = 0.004) and better performance on structured encoding (p = 0.011) and unstructured memory retention (p = 0.009). These findings highlight the importance of lifetime depression history and antidepressant use on the hippocampus and encoding and memory retention in naMCI.

Computerised cognitive training in Parkinson's disease: a protocol for a systematic review and updated meta-analysis.

INTRODUCTION: Cognitive impairment is recognised as an important non-motor symptom in Parkinson's disease (PD) and there is a need for evidence-based non-pharmacological interventions that may prevent or slow cognitive decline in this patient group. One such intervention is computerised cognitive training (CCT), which has shown efficacious for cognition across older adult populations. This systematic review aims to investigate the efficacy of CCT across cognitive, psychosocial and functional domains for people with PD and examine study and intervention design factors that could moderate CCT effects on cognition. METHODS AND ANALYSIS: Randomised controlled trials investigating the effects of CCT in patients with PD without dementia, on cognitive, psychosocial or functional outcomes, will be included. The primary outcome is overall cognitive function. Secondary outcomes are domain-specific cognitive function, psychosocial functioning and functional abilities. We systematically searched MEDLINE, Embase and PsycINFO through 14 May 2020 to identify relevant literature. Risk of bias will be assessed using the revised Cochrane Risk of Bias tool. Effect sizes will be calculated as standardised mean difference of baseline to postintervention change (Hedges' g) with 95% CI for each eligible outcome measure. Pooling of outcomes across studies will be conducted using random-effects models, accounting for dependency structure of effect sizes within studies. Heterogeneity will be assessed using τ2 and I2 statistic. Potential moderators, based on key study and intervention design factors, will be investigated using mixed-effects meta-regression models. ETHICS AND DISSEMINATION: No ethical approval is required. The findings will be disseminated in a peer-reviewed scientific journal. PROSPERO REGISTRATION NUMBER: CRD42020185386.

Memory Performance Correlates of Hippocampal Subfield Volume in Mild Cognitive Impairment Subtype.

The increased understanding that neuropathology begins decades before symptom onset, has led to the conceptualization and widespread utilization of Mild Cognitive Impairment (MCI) as an important transitional state between healthy aging and dementia. Further subcategorization to MCI subtype has led to more distinct prognoses and it is widely considered that amnestic and non-amnestic MCI (aMCI, naMCI) likely have distinct pathophysiologies. Yet, accurately classification remains contentious. Here, we differentiate hippocampal subfield volume between subtypes, diagnosed according to stringent clinical consensus criteria, where aMCI is characterized based on deficits in delayed recall (rather than encoding). We then identify memory performance correlates to subfield volume and associations with long-term cognitive performance and outcome. 3D T1-weighted structural MRI was acquired in 142 participants recruited from the Healthy Brain Aging (HBA) Clinic and diagnosed with aMCI (n = 38), naMCI (n = 84) or subjective memory complaints (SMC; n = 20). T1-weighted datasets were processed with the cortical and hippocampal subfield processing streams in FreeSurfer (v6.0). Subfield volumes, and associations with baseline and longitudinal objective memory scores were then examined. Subfield volumes were found to differentiate clinical profiles: subiculum, CA1, CA4 and dentate gyrus volumes were significantly reduced in aMCI compared to both naMCI and SMC. CA1 subfield volume was shown to predict concurrent memory performance in aMCI, while dentate gyrus volume significantly predicted longitudinal verbal learning and memory decline in the entire cohort. Our findings demonstrate that using a more stringent diagnostic approach to characterizing aMCI is well justified, as delayed recall deficits are strongly linked to underlying volumetric subfield reductions in CA1, CA4 and the dentate gyrus, subfields known to be associated with mnemonic processes. Further research is now warranted to replicate these findings in other MCI samples.

Computerized Cognitive Training in Multiple Sclerosis: A Systematic Review and Meta-analysis.

Background. Cognitive impairments are common in people with multiple sclerosis (MS). Systematic reviews reported promising evidence for various cognitive interventions in this population. Computerized cognitive training (CCT) has strong evidence for safety and efficacy in several populations, but its effects in MS have yet to be specified. Objective. We aimed to synthesize the evidence from randomized controlled trials (RCTs) investigating the effects of CCT on cognitive, psychosocial, and functional outcomes in adults with MS. Method. We searched MEDLINE, EMBASE, PsycINFO, CINAHL, and CENTRAL from inception to March 2019. We calculated standardized mean difference (Hedges' g) of change from baseline in untrained measures of cognition, individual domains, psychosocial functioning, and daily function between CCT and control groups using a random-effects model. Results. A total of 20 RCTs encompassing 982 participants (78% with relapsing-remitting MS) were included. The overall cognitive effect size was moderate (g = 0.30; 95% CI = 0.18-0.43), with no evidence of small-study effect or between-study heterogeneity (prediction interval = 0.17-0.44). Small to moderate effect sizes were found for attention/processing speed, executive functions, and verbal and visuospatial memory. Evidence for working memory, fatigue, and psychosocial and daily functioning were inconclusive. Cognitive effects waned without further training. Conclusions. CCT is efficacious for overall and key cognitive domains in adults with MS, but efficacy on other outcomes and in progressive subtypes remains unclear. Long-term and well-powered trials with diverse cohorts are needed to optimize and maintain the efficacy of CCT, investigate transfer to daily living, and determine who can benefit and whether CCT is a cost-effective strategy to attenuate cognitive decline in MS.

Cognitive training in Parkinson disease: A systematic review and meta-analysis.

OBJECTIVE: To quantify the effects of cognitive training (CT) on cognitive and behavioral outcome measures in patients with Parkinson disease (PD). METHODS: We systematically searched 5 databases for randomized controlled trials (RCTs) of CT in patients with PD reporting cognitive or behavioral outcomes. Efficacy was measured as standardized mean difference (Hedges g) of post-training change. RESULTS: Seven studies encompassing 272 patients with Hoehn & Yahr Stages 1-3 were included. The overall effect of CT over and above control conditions was small but statistically significant (7 studies: g = 0.23, 95% confidence interval [CI] 0.014-0.44, p = 0.037). True heterogeneity across studies was low (I(2) = 0%) and there was no evidence of publication bias. Larger effect sizes were noted on working memory (4 studies: g = 0.74, CI 0.32-1.17, p = 0.001), processing speed (4 studies: g = 0.31, CI 0.01-0.61, p = 0.04), and executive function (5 studies: g = 0.30, CI 0.01-0.58, p = 0.042), while effects on measures of global cognition (4 studies), memory (5 studies), visuospatial skills (4 studies), and depression (5 studies), as well as attention, quality of life, and instrumental activities of daily living (3 studies each), were not statistically significant. No adverse events were reported. CONCLUSIONS: Though still small, the current body of RCT evidence indicates that CT is safe and modestly effective on cognition in patients with mild to moderate PD. Larger RCTs are necessary to examine the utility of CT for secondary prevention of cognitive decline in this population.