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Movement Disorders : Official Journal... Jul 2024Patients in late-stage Parkinson's disease (PD) are caregiver-dependent, have low quality of life, and higher healthcare costs.
BACKGROUND
Patients in late-stage Parkinson's disease (PD) are caregiver-dependent, have low quality of life, and higher healthcare costs.
OBJECTIVE
To estimate the prevalence of PD patients in the current US healthcare system.
METHODS
We downloaded the 2010-2022 data from the TriNetX Diamond claims network that consists of 92 US healthcare sites. PD was identified using standard diagnosis codes, and PD was identified by the usage of wheelchair dependence, personal care assistance, and/or presence of diagnoses of dementia. Age of PD identification and survival information were obtained and stratified by demographic and the disability subgroups.
RESULTS
We identified 1,031,377 PD patients in the TriNetX database. Of these, 18.8% fitted our definition of PD (n = 194,297), and 10.2% met two or more late-stage criteria. Among all PD, the mean age of PD identification was 78.1 (±7.7) years, and 49% were already reported as deceased. PD patients were predominantly male (58.5%) with similar distribution across PD subgroups. The majority did not have race (71%) or ethnicity (69%) information, but for the available information >90% (n = 53,162) were White, 8.2% (n = 5121) Hispanic/Latino, 7.8% (n = 4557) Black, and <0.01% (n = 408) Asian. Of the PD cohort, 71.6% identified with dementia, 12.9% had personal care assistance, and 4.8% were wheelchair-bound.
CONCLUSIONS
Late-stage patients are a significant part of the PD landscape in the current US healthcare system, and largely missed by traditional motor-based disability staging. It is imperative to include this population as a clinical, social, and research priority. © 2024 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.
PubMed: 38962960
DOI: 10.1002/mds.29900 -
Alzheimer's & Dementia : the Journal of... Jul 2024Physical activity is associated with reduced risk of cognitive and functional decline but scalable, sustainable interventions for populations at risk for Alzheimer's...
INTRODUCTION
Physical activity is associated with reduced risk of cognitive and functional decline but scalable, sustainable interventions for populations at risk for Alzheimer's disease (AD) and AD and related dementias (ADRD) are lacking.
METHODS
A 12-week randomized-controlled trial was conducted with a 3-week follow-up using a national AD prevention registry (GeneMatch). The control group (n = 50) set step goals and received daily feedback. The intervention group (n = 44) also received a behaviorally designed game based on achieving step goals and reinforced by a support partner.
RESULTS
Intervention participants (94 participants, mean age 70, 78% female) had greater change in mean daily step count than control of 1699 steps/day (95% confidence interval [CI], 1149-2249), P < 0.0001, which was sustained in the follow-up period at 1219 steps/day (95% CI, 455-1983), P = 0.0018. Carriers of the apolipoprotein E ε4 gene (high risk) did not perform differently than non-carriers; however, high self-reported risk perception was associated with higher activity.
DISCUSSION
A gamified intervention was effective in promoting and sustaining higher physical activity in older adults at genetic risk for AD/ADRD.
HIGHLIGHTS
A simple game played with a support partner increased walking in older adults at risk for Alzheimer's disease (AD). The game also increased minutes of moderate-to-vigorous physical activity per day. Perception of lifelong AD risk was associated with increased activity but genetic risk (apolipoprotein E ε4+) was not.
TRIAL REGISTRATION
ClinicalTrials.gov: NCT05069155.
PubMed: 38962958
DOI: 10.1002/alz.14058 -
International Journal of... Jul 2024Communication partner training is a recommended intervention for partners of people with acquired brain injury. In this paper we explore the past, present, and future of... (Review)
Review
PURPOSE
Communication partner training is a recommended intervention for partners of people with acquired brain injury. In this paper we explore the past, present, and future of communication partner training (CPT) based on our 2023 Speech Pathology Australia national conference address.
METHOD
We focus on our research team's contributions, and highlight research knowledge across stroke, traumatic brain injury (TBI), and dementia. This work is anchored in the voice of people with communication disability. One partner in the CPT journey, Rosey Morrow, co-authors this paper.
RESULT
The CPT evidence base for acquired neurological conditions is growing, including in the areas of technology, co-design, and translation. However, knowledge and implementation gaps remain.
CONCLUSION
The future of CPT will require us to harness co-design and technology, whilst meeting the implementation challenges of complex systems to enable communication for all.
PubMed: 38962904
DOI: 10.1080/17549507.2024.2362856 -
Frontiers in Neurology 2024Executive dysfunction is a core symptom of vascular cognitive impairment (VCI), which seriously affects patients' prognosis. This paper aims to investigate the...
OBJECTIVE
Executive dysfunction is a core symptom of vascular cognitive impairment (VCI), which seriously affects patients' prognosis. This paper aims to investigate the effectiveness of rTMS on executive function in VCI.
METHODS
The databases selected for this study included Pubmed, Embase, Cochrane Library, China National Knowledge Infrastructure (CNKI), Wanfang, China Science and Technology Journal Database (VIP), and China Biology Medicine Disc (CBM). The screening times were conducted from the time of library construction until August 23, 2023. The inclusion criteria for this meta-analysis were randomized controlled trials (RCTs) on rTMS for VCI, which include executive function scores. The primary metrics were executive subscale scores of the Cognitive Comprehensive Scale and total scores of the Executive Specificity Scale. The secondary metrics were subscale scores of the Executive Specificity Scale. The quality of each eligible study was assessed using the Cochrane Risk of Bias tool. Meta-analysis and bias analysis were performed using Stata (version 16.0) and RevMan (version 5.3).
RESULTS
A total of 20 high-quality clinical RCTs with 1,049 samples were included in this paper. The findings from the primary outcomes revealed that within the rTMS group, there were significantly higher scores observed for the executive sub-item on the cognitive composite scale (SMD = 0.93, 95% CI = 0.77-1.08, < 0.00001, = 14%) and the total score on the executive specific scale (SMD = 0.69, 95% CI = 0.44-0.94, < 0.00001, = 0%) compared to the control group. As for the secondary outcome measures, as shown by the Trail Making Test-A (time) (MD = -35.75, 95% CI = -68.37 to -3.12, = 0.03, = 55%), the Stroop-C card (time) (SMD = -0.46, 95% CI = -0.86 to -0.06, = 0.02, = 0%) and the Stroop-C card (correct number) (SMD = 0.49, 95% CI = 0.04-0.94, = 0.03, = 0%), the experimental group shorts time and enhances accuracy of executive task in comparison to the control group. Subgroup analysis of the main outcome demonstrated that intermittent theta burst stimulation (iTBS), higher frequency, lower intensity, longer duration, and combined comprehensive therapy exhibited superior efficacy.
CONCLUSION
rTMS is effective in the treatment of the executive function of VCI. The present study has some limitations, so multi-center, large-sample, objective indicators and parameters are needed to further explore in the future.https://www.crd.york.ac.uk/prospero/, CRD42023459669.
PubMed: 38962482
DOI: 10.3389/fneur.2024.1374395 -
Frontiers in Nutrition 2024As the world's population ages the prevalence of age-related health concerns is increasing, including neurodegeneration disorders such as mild cognitive impairment,... (Review)
Review
As the world's population ages the prevalence of age-related health concerns is increasing, including neurodegeneration disorders such as mild cognitive impairment, vascular dementia and Alzheimer's disease. Diet is a key modifiable risk factor for the development of neurodegeneration, likely due to gut-brain axis interactions related to neuroinflammation. Analyses of dietary patterns identified dairy as being part of a cognitively healthy diet; however, its contribution to cognitive outcomes is difficult to discern. This narrative review evaluates the literature to determine whether there is sufficient evidence that the consumption of dairy products helps to maintain cognitive function in later life. A search using the terms (dairy OR milk OR cheese OR yogurt OR yogurt) AND ("mild cognitive impairment" OR dementia OR "Alzheimer's disease") identified 796 articles. After screening and sorting, 23 observational studies and 6 intervention studies were identified. The results of the observational studies implied that the relationship between total dairy consumption and cognitive outcomes is inverse U-shaped, with moderate consumption (1-2 servings per day) being the most beneficial. The analysis of the intake of different types of dairy products indicated that fermented products, particularly cheese, were most likely responsible for the observed benefits. The experimental studies all used dairy-derived peptides produced during fermentation as the dietary intervention, and the results indicated that these could be an effective treatment for early-stage cognitive impairment. Further experimental studies with whole dairy products, particularly fermented dairy, are needed to determine whether the regular consumption of these foods should be recommended to maximize the likelihood of healthy cognitive aging.
PubMed: 38962439
DOI: 10.3389/fnut.2024.1366949 -
Australian Prescriber Jun 2024Established drug therapies for Alzheimer disease (cholinesterase inhibitors and memantine) do not modify the disease course and provide only modest clinical benefit.... (Review)
Review
Established drug therapies for Alzheimer disease (cholinesterase inhibitors and memantine) do not modify the disease course and provide only modest clinical benefit. Biomarker measures of amyloid, tau and neurodegeneration have been integral to Alzheimer disease clinical trials for biologic drugs, for patient selection and efficacy monitoring. At the time of writing, two monoclonal antibodies targeting the amyloid-beta protein (aducanumab and lecanemab) have been approved in the USA, and two agents (lecanemab and donanemab) are under evaluation by the Therapeutic Goods Administration in Australia. Clinical trials have demonstrated that monoclonal antibodies are effective at removing amyloid from the brain in people with early Alzheimer disease. Cognitive benefits are statistically significant, but do not achieve the minimal clinically important difference. Amyloid-related imaging abnormalities of vasogenic oedema and microhaemorrhages occur more frequently on treatment; although these are usually asymptomatic or transient, in some people they are serious or fatal. Targeting amyloid as a unimodal strategy is unlikely to be sufficient and future therapies may need to be multimodal, targeting multiple pathogenic pathways. The burden of dementia is greatest in the older population where mixed dementia pathology dominates; the relationship between biomarkers, clinical phenotype and pathology attenuates; and frailty and comorbidity impact cognition. This creates challenges in identifying effective therapies for the group where dementia is most prevalent.
PubMed: 38962384
DOI: 10.18773/austprescr.2024.021 -
Frontiers in Psychology 2024Few studies have examined the association of loneliness and cognitive functioning in the US. We used two common measures of loneliness and examined their association in...
INTRODUCTION
Few studies have examined the association of loneliness and cognitive functioning in the US. We used two common measures of loneliness and examined their association in a large sample of US Black, Latino, and White adults (ages ≥ 50).
METHODS
We analyzed Wave 3 of the National Social Life, Health, and Aging Project ( = 2,757). We examined loneliness using one item from the CES-D and the Felt Loneliness Measure (NFLM); cognitive functioning was assessed using the Montreal Cognitive Assessment (MoCA) tool, where higher scores indicated better functioning. We used weighted ordinary least squares regressions to examine the effects of loneliness (CES-D loneliness and NFLM in separate models) on MoCA scores. In exploratory analyses, we examined if these relationships varied by race and ethnicity. We adjusted all models for sociodemographic and other salient factors (e.g., chronic disease, depressive symptoms, living alone).
RESULTS
Mean age was 63.49 years, 52% were female, and 9% were Black and 6% Latino persons. Approximately 54% endorsed feeling lonely on at least one measure; 31% (CES-D) and 46% (NFLM). The relationship between loneliness measures was positive and significant, (1, = 2,757) = 435.493 < 0.001. However, only 40% of lonely individuals were identified as lonely on both assessments. CES-D loneliness was inversely (βˆ = -0.274, = 0.032) associated with MoCA scores and this association did not vary by race and ethnicity. Greater NFLM loneliness was positively associated (βˆ = 0.445, < 0.001) with higher MoCA scores for
DISCUSSION
Loneliness appears to be an important predictor of cognitive functioning. However, the association of loneliness and cognitive functioning varied when using the CES-D loneliness item or the NFLM. Future work is needed to understand how loneliness and its clinically relevant dimensions (social, emotional, existential, chronicity) relate to global and individual cognitive domains. Research is needed with racially and ethnically diverse midlife and older adults, particularly to understand our counterintuitive finding for Latino participants. Finally, findings also support the need for research on interventions to prevent cognitive decline targeting loneliness.
PubMed: 38962235
DOI: 10.3389/fpsyg.2024.1344044 -
Oxidative Medicine and Cellular... 2024Approximately 70% of all strokes occur in patients over 65 years old, and stroke increases the risk of developing dementia. The circle of Willis (CoW), the ring of...
Approximately 70% of all strokes occur in patients over 65 years old, and stroke increases the risk of developing dementia. The circle of Willis (CoW), the ring of arteries at the base of the brain, links the intracerebral arteries to one another to maintain adequate cerebral perfusion. The CoW proteome is affected in cerebrovascular and neurodegenerative diseases, but changes related to aging have not been described. Here, we report on a quantitative proteomics analysis comparing the CoW from five young (2-3-month-old) and five aged male (18-20-month-old) mice using gene ontology (GO) enrichment, ingenuity pathway analysis (IPA), and iPathwayGuide tools. This revealed 242 proteins that were significantly dysregulated with aging, among which 189 were upregulated and 53 downregulated. GO enrichment-based analysis identified blood coagulation as the top biological function that changed with age and integrin binding and extracellular matrix constituents as the top molecular functions. Consistent with these findings, iPathwayGuide-based impact analysis revealed associations between aging and the complement and coagulation, platelet activation, ECM-receptor interaction, and metabolic process pathways. Furthermore, IPA analysis revealed the enrichment of 97 canonical pathways that contribute to inflammatory responses, as well as 59 inflammation-associated upstream regulators including 39 transcription factors and 20 cytokines. Thus, aging-associated changes in the CoW proteome in male mice demonstrate increases in metabolic, thrombotic, and inflammatory processes.
Topics: Animals; Circle of Willis; Aging; Male; Proteome; Mice; Vascular Diseases; Mice, Inbred C57BL; Proteomics
PubMed: 38962180
DOI: 10.1155/2024/4887877 -
Frontiers in Neuroscience 2024Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in... (Review)
Review
Unmatched by other non-invasive brain stimulation techniques, transcranial ultrasound (TUS) offers highly focal stimulation not only on the cortical surface but also in deep brain structures. These unique attributes are invaluable in both basic and clinical research and might open new avenues for treating neurological and psychiatric diseases. Here, we provide a concise overview of the expanding volume of clinical investigations in recent years and upcoming research initiatives concerning focused ultrasound neuromodulation. Currently, clinical TUS research addresses a variety of neuropsychiatric conditions, such as pain, dementia, movement disorders, psychiatric conditions, epilepsy, disorders of consciousness, and developmental disorders. As demonstrated in sham-controlled randomized studies, TUS neuromodulation improved cognitive functions and mood, and alleviated symptoms in schizophrenia and autism. Further, preliminary uncontrolled evidence suggests relieved anxiety, enhanced motor functions in movement disorders, reduced epileptic seizure frequency, improved responsiveness in patients with minimally conscious state, as well as pain reduction after neuromodulatory TUS. While constrained by the relatively modest number of investigations, primarily consisting of uncontrolled feasibility trials with small sample sizes, TUS holds encouraging prospects for treating neuropsychiatric disorders. Larger sham-controlled randomized trials, alongside further basic research into the mechanisms of action and optimal sonication parameters, are inevitably needed to unfold the full potential of TUS neuromodulation.
PubMed: 38962179
DOI: 10.3389/fnins.2024.1420255 -
Nanotheranostics 2024The blood-brain barrier (BBB) is a major bottleneck in delivering therapeutics to the brain. Treatment strategies to transiently open this barrier include focused...
The blood-brain barrier (BBB) is a major bottleneck in delivering therapeutics to the brain. Treatment strategies to transiently open this barrier include focused ultrasound combined with intravenously injected microbubbles (FUS) and targeting of molecules that regulate BBB permeability. Here, we investigated BBB opening mediated by the claudin-5 binder cCPEm (a microorganismal toxin in a truncated form) and FUS at a centre frequency of 1 MHz, assessing dextran uptake, broadband emission, and endogenous immunoglobulin G (IgG) extravasation. FUS-induced BBB opening was detectable at a pressure ≥0.35 MPa when assessed for leakage of 10 and 70 kDa dextran, and at ≥0.2 MPa for uptake of endogenous IgG. Treating mice with 20 mg/kg cCPEm failed to open the BBB, and pre-treatment with cCPEm followed by FUS at 0.2 and 0.3 MPa did not overtly increase BBB opening compared to FUS alone. Using passive cavitation detection (PCD), we found that broadband emission correlated with the peak negative pressure (PNP) and dextran leakage, indicating the possibility of using broadband emission for developing a feedback controller to monitor BBB opening. Together, our study highlights the challenges in developing combinatorial approaches to open the BBB and presents an additional IgG-based histological detection method for BBB opening.
Topics: Animals; Blood-Brain Barrier; Mice; Claudin-5; Microbubbles; Immunoglobulin G; Ultrasonic Waves; Mice, Inbred C57BL; Dextrans
PubMed: 38961889
DOI: 10.7150/ntno.95146