Frontiers in Dementia最新文献

{"title":"Beneficial effects of physical exercise and an orally active mGluR2/3 antagonist pro-drug on neurogenesis and behavior in an Alzheimer's amyloidosis model","authors":"Georgina S. Perez Garcia, Mesude Bicak, Jacqueline Buros, Jean-Vianney Haure-Mirande, G. Perez, Alena Otero-Pagan, M. A. Gama Sosa, R. De Gasperi, Mary Sano, Fred H. Gage, Carrolee Barlow, Joel T. Dudley, B. Glicksberg, Yanzhuang Wang, B. Readhead, M. Ehrlich, G. Elder, Samuel Gandy","doi":"10.3389/frdem.2023.1198006","DOIUrl":"https://doi.org/10.3389/frdem.2023.1198006","url":null,"abstract":"Modulation of physical activity represents an important intervention that may delay, slow, or prevent mild cognitive impairment (MCI) or dementia due to Alzheimer's disease (AD). One mechanism proposed to underlie the beneficial effect of physical exercise (PE) involves the apparent stimulation of adult hippocampal neurogenesis (AHN). BCI-838 is a pro-drug whose active metabolite BCI-632 is a negative allosteric modulator at group II metabotropic glutamate receptors (mGluR2/3). We previously demonstrated that administration of BCI-838 to a mouse model of brain accumulation of oligomeric AβE22Q (APPE693Q = “Dutch APP”) reduced learning behavior impairment and anxiety, both of which are associated with the phenotype of Dutch APP mice.3-month-old mice were administered BCI-838 and/or physical exercise for 1 month and then tested in novel object recognition, neurogenesis, and RNAseq.Here we show that (i) administration of BCI-838 and a combination of BCI-838 and PE enhanced AHN in a 4-month old mouse model of AD amyloid pathology (APPKM670/671NL/PSEN1Δexon9= APP/PS1), (ii) administration of BCI-838 alone or with PE led to stimulation of AHN and improvement in recognition memory, (iii) the hippocampal dentate gyrus transcriptome of APP/PS1 mice following BCI-838 treatment showed up-regulation of brain-derived neurotrophic factor (BDNF), PIK3C2A of the PI3K-mTOR pathway, and metabotropic glutamate receptors, and down-regulation of EIF5A involved in modulation of mTOR activity by ketamine, and (iv) validation by qPCR of an association between increased BDNF levels and BCI-838 treatment.Our study points to BCI-838 as a safe and orally active compound capable of mimicking the beneficial effect of PE on AHN and recognition memory in a mouse model of AD amyloid pathology.","PeriodicalId":408305,"journal":{"name":"Frontiers in Dementia","volume":"36 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"122381463","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Adherence to cognitive and physical exercise engagement: a challenge to successful dementia risk reduction and prevention efforts","authors":"Therese M. O'Neil-Pirozzi, Davide B. Cappon, Alvaro Pascual-Leone","doi":"10.3389/frdem.2023.1254986","DOIUrl":"https://doi.org/10.3389/frdem.2023.1254986","url":null,"abstract":"With human life expectancy and proportion of older adults increasing, global use of evidence-supported preventative methods to minimize risk of brain-related disabilities such as Alzheimer's disease and other dementias—as well as interventions to slow rate of disease progression—is important. Sustained engagement in cognitive and physical exercise programs may prevent or delay dementia onset as well as maximize health and function of those with dementia. Despite awareness of the importance of cognitive and physical exercise to brain health, exercise program adherence by older adults is extremely challenging. In this Perspective article, we summarize what is known about contributors to exercise program adherence and strategies to promote it. We discuss our viewpoint on knowledge gaps regarding exercise adherence and research that needs to be conducted. We conclude by proposing a multi-dimensional exercise adherence assessment framework that includes portable neurophysiologic technologies to inform initial design and updating of individualized exercise programs that optimize sustained exercise program engagement and, ultimately, maximize brain health in older adults with and without mild cognitive impairment and dementia.","PeriodicalId":408305,"journal":{"name":"Frontiers in Dementia","volume":"65 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-09-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126506323","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Dimensions of cognitive reserve and their predictive power of cognitive performance and decline in the elderly","authors":"T. del Ser, Elizabeth Valeriano-Lorenzo, L. Jáñez-Escalada, M. Avila-Villanueva, B. Frades, María-Ascensión Zea, M. Valentí, Linda Zhang, M. Fernández-Blázquez","doi":"10.3389/frdem.2023.1099059","DOIUrl":"https://doi.org/10.3389/frdem.2023.1099059","url":null,"abstract":"The relative importance of different components of cognitive reserve (CR), as well as their differences by gender, are poorly established.To explore several dimensions of CR, their differences by gender, and their effects on cognitive performance and trajectory in a cohort of older people without relevant psychiatric, neurologic, or systemic conditions.Twenty-one variables related to the education, occupation, social activities, and life habits of 1,093 home-dwelling and cognitively healthy individuals, between 68 and 86 years old, were explored using factorial analyses to delineate several dimensions of CR. These dimensions were contrasted with baseline cognitive performance, follow-up over 5 years of participants' cognitive trajectory, conversion to mild cognitive impairment (MCI), and brain volumes using regression and growth curve models, controlling for gender, age, marital status, number of medications, trait anxiety, depression, and ApoE genotype.Five highly intercorrelated dimensions of CR were identified, with some differences in their structure and effects based on gender. Three of them, education/occupation, midlife cognitive activities, and leisure activities, were significantly associated with late-life cognitive performance, accounting for more than 20% of its variance. The education/occupation had positive effect on the rate of cognitive decline during the 5-year follow up in individuals with final diagnosis of MCI but showed a reduced risk for MCI in men. None of these dimensions showed significant relationships with gray or white matter volumes.Proxy markers of CR can be represented by five interrelated dimensions. Education/occupation, midlife cognitive activities, and leisure activities are associated with better cognitive performance in old age and provide a buffer against cognitive impairment. Education/occupation may delay the clinical onset of MCI and is also associated with the rate of change in cognitive performance.","PeriodicalId":408305,"journal":{"name":"Frontiers in Dementia","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"129452776","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Cognitive aging in rural communities: preliminary memory characterization of a community cohort from Southern Nevada","authors":"Justin B. Miller, C. Wong, J. Caldwell, Jessica Rodrigues, Shehroo B. Pudumjee, Samantha E John, A. Ritter","doi":"10.3389/frdem.2023.1236039","DOIUrl":"https://doi.org/10.3389/frdem.2023.1236039","url":null,"abstract":"Rural-dwelling older adults face unique health challenges that may increase risk for Alzheimer's disease and dementia but are underrepresented in aging research. Here, we present an initial characterization of a rural community cohort compared to an urban cohort from the same region.Adults over age 50 living in a non-metropolitan area are clinically characterized using the Uniform Data Set, enriched with additional measures of verbal and non-verbal memory measures. Neighborhood disadvantage is also assessed. Clinical and cognitive differences between cohorts were explored after stratifying by cognitive impairment.Between group comparisons found that rural-dwellers demonstrated better verbal memory than urban-dwellers on primary indices of learning, recall, and recognition, with small to medium effects in overall comparisons. When stratified by impairment, rural-urban differences were notably larger among cognitively normal individuals. Within-group comparisons found that the magnitude of impairment between cognitively normal and impaired groups was greater among rural-dwellers compared to urban-dwellers. No differences in non-verbal memory or overall clinical status were found, and there were no effects of neighborhood disadvantage on any cognitive measure.Living in a rural community presents a complex set of contextual factors that for some, may increase risk for dementia. In this study, we found small to moderate memory advantages for rural-dwellers, leaving open the possibility that late-life rural living may be advantageous for some and promote resilience. Additional prospective research is critically needed to better understand the factors that influence aging outcomes in this underrepresented population.","PeriodicalId":408305,"journal":{"name":"Frontiers in Dementia","volume":"26 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133806727","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Case report: Anti-ARHGAP26 autoantibodies in atypical dementia with Lewy bodies","authors":"Niels Hansen, K. Rentzsch, S. Hirschel, J. Wiltfang, B. Schott, C. Bartels, C. Lange, C. Bouter","doi":"10.3389/frdem.2023.1227823","DOIUrl":"https://doi.org/10.3389/frdem.2023.1227823","url":null,"abstract":"Dementia with Lewy bodies (DLB) is the second most common type of neurodegenerative dementia. Here, we report a case of dementia associated with anti-Rho-GTPase-activating protein 26 (ARHGAP26) autoantibodies, which have never been previously linked to DLB.We describe the case of a 78-year-old man who underwent cerebrospinal fluid (CSF) analysis, magnetic resonance imaging (MRI), 18F-fluorodesoxyglucose positron emission tomography (FDG-PET), and a detailed neuropsychological evaluation.The patient presented with mild dementia syndrome associated with extrapyramidal symptoms. Neuropsychological testing revealed impaired cognitive flexibility, figural memory, and verbal memory. Fluctuating cognitive abilities with deficits in attention-executive dysfunction and visuoconstruction also developed over time. A brain MRI showed reduced biparietal and cerebellar brain volume with generalized accentuation of the outer CSF spaces. The patient's CSF revealed anti-ARHGAP26 autoantibodies, which were also detectable in serum. In the differential complementary imaging diagnosis at 2 years, an FDG-PET revealed decreased occupancy of the posterior cingulum and precuneus. Although the FDG-PET, MRI, and clinical findings were potentially consistent with Alzheimer's disease, negative amyloid biomarkers in the CSF made an AD diagnosis highly unlikely. Single photon emission computed tomography (SPECT) with [(123)I] N-omega-fluoropropyl-2beta-carbomethoxy-3beta-{4-iodophenyl}nortropane ([(123)I]FP-CIT) showed right-sided predominance, reduced dopamine transporter uptake in the putamen, consistent with a positive indicative biomarker finding typical of DLB. Considering the clinically probable DLB associated with the two core features of Parkinsonism and fluctuating cognition with deficits in attention, supported by an abundant tracer uptake in the right putamen and lower uptake in the left putamen on 123I-FP-CIT-SPECT as an indicative biomarker, we started an antidementia drug using a cholinesterase inhibitor.Our report shows that atypical DLB may be associated with anti-ARHGAP26 autoantibodies, although their role and significance in the pathogenesis of DLB are unknown. However, it has to be mentioned that it is also possible that antibody-specific synthesis of anti-ARHGAP26 autoantibodies is a hallmark of a rare autoimmune disease that may cause the clinical and laboratory features involving altered dopamine transporter uptake on 123I-FP-CIT-SPECT, dementia, and mild Parkinson's symptoms rather than idiopathic DLB with only two core DLB features and inconsistent cognitive and imaging findings. Further research is needed to investigate the role of these autoantibodies in different dementias, particularly in DLB and mixed DLB-AD types.","PeriodicalId":408305,"journal":{"name":"Frontiers in Dementia","volume":"PP 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-03","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"126434028","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Limited evidence of a shared genetic relationship between C-reactive protein levels and cognitive function in older UK adults of European ancestry","authors":"Amy E. Packer, A. Corbett, R. Arathimos, C. Ballard, D. Aarsland, A. Hampshire, D. Dima, B. Creese, M. Malanchini, T. Powell","doi":"10.3389/frdem.2023.1093223","DOIUrl":"https://doi.org/10.3389/frdem.2023.1093223","url":null,"abstract":"Previous studies have shown associations between cognitive function and C-reactive protein (CRP) levels in older adults. Few studies have considered the extent to which a genetic predisposition for higher CRP levels contributes to this association.Data was analyzed from 7,817 UK participants aged >50 years as part of the PROTECT study, within which adults without dementia completed a comprehensive neuropsychological battery. We constructed a polygenic risk score (PRS-CRP) that explained 9.61% of the variance in serum CRP levels (p = 2.362 × 10−7) in an independent cohort. Regressions were used to explore the relationship between PRS-CRP and cognitive outcomes.We found no significant associations between PRS-CRP and any cognitive measures in the sample overall. In older participants (>62 years), we observed a significant positive association between PRS-CRP and self-ordered search score (i.e., spatial working memory).Whilst our results indicate a weak positive relationship between PRS-CRP and spatial working memory that is specific to older adults, overall, there appears to be no strong effects of PRS-CRP on cognitive function.","PeriodicalId":408305,"journal":{"name":"Frontiers in Dementia","volume":"15 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-08-02","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"121767219","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Primary care biomarkers and dementia in people of the Torres Strait, Australia: extended data analysis","authors":"F. Thompson, S. Russell, R. Quigley, Malcolm I McDonald, B. Sagigi, Sean M Taylor, Sandy Campbell, B. Schmidt, A. Esterman, L. Harriss, Gavin Miller, Phillip Mills, E. Strivens, R. Mcdermott","doi":"10.3389/frdem.2023.1218709","DOIUrl":"https://doi.org/10.3389/frdem.2023.1218709","url":null,"abstract":"Dementia disproportionately affects First Nations populations. Biomarkers collected in primary care may assist with determining dementia risk. Our previous underpowered study showed some suggestive associations between baseline biomarkers with follow-up dementia or cognitive impairment. The current study extended this work with a larger linked dataset.Probabilistic data linkage was used to combine four baseline datasets with one follow-up assessment of dementia status 0–20 years later in a First Nations population in Australia. Mixed Effects Generalized Linear Regression models were used to test associations between baseline measures and follow-up status, accounting for repeated measures within individuals.Linked data were available for 88 individuals, with 101–279 baseline observations, depending on the type of measure. Higher urinary albumin to creatine ratio was associated with greater risk of cognitive impairment/dementia, whereas body weight and key lipid markers were negatively associated. There was no clear trend when these associations were examined by timing of measurement (i.e., ≤10 years or >10 years before a dementia assessment).The results of this study support findings from our previous work and indicate that microalbuminuria can be an early indicator of dementia risk in this population. The weight and lipid profile findings reflect the mixed results in the published literature and require further investigation and interpretation.","PeriodicalId":408305,"journal":{"name":"Frontiers in Dementia","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"130611902","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"An alternative method of SNP inclusion to develop a generalized polygenic risk score analysis across Alzheimer's disease cohorts","authors":"K. Brookes, Tamar Guetta‐Baranés, Alan Thomas, K. Morgan","doi":"10.3389/frdem.2023.1120206","DOIUrl":"https://doi.org/10.3389/frdem.2023.1120206","url":null,"abstract":"Polygenic risk scores (PRSs) have great clinical potential for detecting late-onset diseases such as Alzheimer's disease (AD), allowing the identification of those most at risk years before the symptoms present. Although many studies use various and complicated machine learning algorithms to determine the best discriminatory values for PRSs, few studies look at the commonality of the Single Nucleotide Polymorphisms (SNPs) utilized in these models.This investigation focussed on identifying SNPs that tag blocks of linkage disequilibrium across the genome, allowing for a generalized PRS model across cohorts and genotyping panels. PRS modeling was conducted on five AD development cohorts, with the best discriminatory models exploring for a commonality of linkage disequilibrium clumps. Clumps that contributed to the discrimination of cases from controls that occurred in multiple cohorts were used to create a generalized model of PRS, which was then tested in the five development cohorts and three further AD cohorts.The model developed provided a discriminability accuracy average of over 70% in multiple AD cohorts and included variants of several well-known AD risk genes.A key element of devising a polygenic risk score that can be used in the clinical setting is one that has consistency in the SNPs that are used to calculate the score; this study demonstrates that using a model based on commonality of association findings rather than meta-analyses may prove useful.","PeriodicalId":408305,"journal":{"name":"Frontiers in Dementia","volume":"19 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-31","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"128910331","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Assessing behavioral and psychological symptoms of dementia: a comprehensive review of current options and future perspectives","authors":"F. Pozzi, Luisa Calì, C. Ferrarese, I. Appollonio, L. Tremolizzo","doi":"10.3389/frdem.2023.1226060","DOIUrl":"https://doi.org/10.3389/frdem.2023.1226060","url":null,"abstract":"The behavioral and psychological symptoms of dementia (BPSD) are a heterogeneous set of challenging disturbances of behavior, mood, perception, and thought that occur in almost all patients with dementia. A huge number of instruments have been developed to assess BPSD in different populations and settings. Although some of these tools are more widely used than others, no single instrument can be considered completely satisfactory, and each of these tools has its advantages and disadvantages. In this narrative review, we have provided a comprehensive overview of the characteristics of a large number of such instruments, addressing their applicability, strengths, and limitations. These depend on the setting, the expertise required, and the people involved, and all these factors need to be taken into account when choosing the most suitable scale or tool. We have also briefly discussed the use of objective biomarkers of BPSD. Finally, we have attempted to provide indications for future research in the field and suggest the ideal characteristics of a possible new tool, which should be short, easy to understand and use, and treatment oriented, providing clinicians with data such as frequency, severity, and triggers of behaviors and enabling them to find appropriate strategies to effectively tackle BPSD.","PeriodicalId":408305,"journal":{"name":"Frontiers in Dementia","volume":"1 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"115490558","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"SARS-CoV-2 amyloid, is COVID-19-exacerbated dementia an amyloid disorder in the making?","authors":"N. Milton","doi":"10.3389/frdem.2023.1233340","DOIUrl":"https://doi.org/10.3389/frdem.2023.1233340","url":null,"abstract":"","PeriodicalId":408305,"journal":{"name":"Frontiers in Dementia","volume":"6 1","pages":"0"},"PeriodicalIF":0.0,"publicationDate":"2023-07-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"133781230","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}