{"title":"Genetics and Neuropathology of Neurodegenerative Dementias.","authors":"Sonja W Scholz, Inma Cobos","doi":"10.1212/CON.0000000000001505","DOIUrl":"10.1212/CON.0000000000001505","url":null,"abstract":"<p><strong>Objective: </strong>This article provides an overview of the current understanding of the genetic and pathologic features of neurodegenerative dementias, with an emphasis on Alzheimer disease and related dementias.</p><p><strong>Latest developments: </strong>In recent years, there has been substantial progress in genetic research, contributing significant knowledge to our understanding of the molecular risk factors involved in neurodegenerative dementia syndromes. Several genes have been linked to monogenic forms of dementia (eg, APP, PSEN1, PSEN2, SNCA, GRN, C9orf72, MAPT) and an even larger number of genetic variants are known to influence susceptibility for developing dementia. As anti-amyloid therapies for patients with early-stage Alzheimer disease have entered the clinical arena, screening for the apolipoprotein E ε4 high-risk allele has come into focus, emphasizing the importance of genetic counseling. Similarly, advances in the pathologic classifications of neurodegenerative dementia syndromes and molecular pathology highlight their heterogeneity and overlapping features and provide insights into the pathogenesis of these conditions.</p><p><strong>Essential points: </strong>Recent progress in neurogenetics and molecular pathology has improved our understanding of the complex pathogenetic changes associated with neurodegenerative dementias, facilitating improved disease modeling, enhanced diagnostics, and individualized counseling. The hope is that this knowledge will ultimately pave the way for the development of novel therapeutics.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"30 6","pages":"1801-1822"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774681","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":"Vascular Cognitive Impairment.","authors":"Lisa C Silbert","doi":"10.1212/CON.0000000000001508","DOIUrl":"10.1212/CON.0000000000001508","url":null,"abstract":"<p><strong>Objective: </strong>Vascular cognitive impairment is a major contributor to age-associated cognitive decline, both independently and as a contributor to mixed dementia syndromes. This article reviews the current understanding of how vascular dysfunction contributes to cognitive impairment and dementia risk in older individuals and includes updated diagnostic criteria and treatment recommendations.</p><p><strong>Latest developments: </strong>Clinical and research criteria have been evolving to more accurately determine the full prevalence of vascular cognitive impairment. The Boston Criteria version 2.0 for cerebral amyloid angiopathy now includes multiple punctate MRI T2 white matter hyperintensities and MR-visible perivascular spaces in addition to previously described T2* hemorrhagic signatures. MR-visible perivascular spaces are associated with both vascular cognitive impairment and Alzheimer disease, potentially linking cerebrovascular dysfunction to neurodegenerative disorders through its role in brain waste clearance. The American Heart Association's goal for cardiovascular health promotion, \"Life's Essential 8,\" has been updated to include sleep health and acknowledges psychological well-being and social determinants of health as fundamental components necessary to achieve optimal cardiovascular health for all adults.</p><p><strong>Essential points: </strong>Vascular cognitive impairment is a common and often underrecognized contributor to cognitive impairment in older individuals, with heterogeneous etiologies requiring individualized treatment strategies. Effective cerebrovascular disease risk factor modification starting in midlife is critical to reducing the risk of Alzheimer disease and related dementias, with the goal of preventing vascular brain injury and maintaining cognitive reserve in the presence of nonvascular age-related brain pathologies.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"30 6","pages":"1699-1725"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774702","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":"Neuroimaging in Dementia.","authors":"Shannon L Risacher","doi":"10.1212/CON.0000000000001509","DOIUrl":"10.1212/CON.0000000000001509","url":null,"abstract":"<p><strong>Objective: </strong>This article captures the current literature regarding the use of neuroimaging measures to study neurodegenerative diseases, including early- and late-onset Alzheimer disease, vascular cognitive impairment, frontotemporal lobar degeneration disorders, dementia with Lewy bodies, and Parkinson disease dementia. In particular, the article highlights significant recent changes in novel therapeutics now available for the treatment of Alzheimer disease and in defining neurodegenerative disease using biological frameworks. Studies summarized include those using structural and functional MRI (fMRI) techniques, as well as metabolic and molecular emission tomography imaging (ie, positron emission tomography [PET] and single-photon emission computerized tomography [SPECT]).</p><p><strong>Latest developments: </strong>Neuroimaging measures are considered essential biomarkers for the detection and diagnosis of most neurodegenerative diseases. The recent approval of anti-amyloid antibody therapies has highlighted the importance of MRI and PET techniques in treatment eligibility and monitoring for associated side effects. Given the success of the initial biomarker-based classification system for Alzheimer disease (the amyloid, tau, neurodegeneration [A/T/N] framework), researchers in vascular cognitive impairment have created similar techniques for biomarker-based diagnosis. Further, the A/T/N framework for Alzheimer disease has been updated to include several pathologic targets for biomarker detection.</p><p><strong>Essential points: </strong>Neurodegenerative diseases have a major health impact on millions of patients around the world. Neuroimaging biomarkers are rapidly becoming major diagnostic tools for the detection, monitoring, and treatment of neurodegenerative diseases. This article educates readers about the current literature surrounding the use of neuroimaging tools in neurodegenerative diseases along with recent important developments in the field.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"30 6","pages":"1761-1789"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774627","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":"Frontotemporal Dementia.","authors":"David Glenn Clark","doi":"10.1212/CON.0000000000001506","DOIUrl":"https://doi.org/10.1212/CON.0000000000001506","url":null,"abstract":"<p><strong>Objective: </strong>This article discusses frontotemporal dementia (FTD) syndromes using a simplified framework of three core syndromes, including details on their pathology and unique genetic variations.</p><p><strong>Latest developments: </strong>FTD includes at least seven major clinical syndromes. The three core syndromes are behavioral variant FTD and two forms of progressive aphasia, commonly referred to as the nonfluent variant and semantic variant of primary progressive aphasia. Clinical features reflect the involvement of major functional brain networks. Derangements of three proteins account for nearly all underlying pathology for FTD syndromes: transactive response DNA-binding protein 43 (TDP-43) (approximately 50% of cases), MAPT (45% of cases), and FUS (5% of cases). The clinical presentation and imaging provide clues to the underlying pathology. FTD is more heritable than Alzheimer disease, with variations in C9orf72, MAPT, or GRN (which encodes progranulin) occurring in more than 10% of FTD cases.</p><p><strong>Essential points: </strong>The framework described here will provide clinicians with a foundation for understanding the complex and heterogeneous set of FTD syndromes. There are currently no disease-modifying or US Food and Drug Administration (FDA)-approved treatments for FTD, but clinical trials are underway, including some targeting presymptomatic genetic variation carriers. Available FTD treatments address deficits in behavior or language nonpharmacologically or through the off-label use of medications approved for other indications. Improvements in biomarkers will accelerate the discovery of new pharmacologic treatments.</p>","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"30 6","pages":"1642-1672"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774678","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":"List of Abbreviations.","authors":"","doi":"10.1212/01.CON.0001095700.45238.1e","DOIUrl":"10.1212/01.CON.0001095700.45238.1e","url":null,"abstract":"","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"30 6","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774624","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":"Table of Contents.","authors":"","doi":"10.1212/CON.0000000000001511","DOIUrl":"https://doi.org/10.1212/CON.0000000000001511","url":null,"abstract":"","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"30 6","pages":"1572-1573"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142958707","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":"Table of Contents.","authors":"","doi":"10.1212/CON.0000000000001511","DOIUrl":"https://doi.org/10.1212/CON.0000000000001511","url":null,"abstract":"","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"30 6","pages":"1572-1573"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144052297","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":"SELF-ASSESSMENT AND CME.","authors":"","doi":"10.1212/CON.0000000000001513","DOIUrl":"https://doi.org/10.1212/CON.0000000000001513","url":null,"abstract":"","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"30 6","pages":"1875"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"144048754","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":"Dementia at the Crossroads of Prediction and Prevention.","authors":"Lyell K Jones","doi":"10.1212/CON.0000000000001538","DOIUrl":"10.1212/CON.0000000000001538","url":null,"abstract":"","PeriodicalId":52475,"journal":{"name":"CONTINUUM Lifelong Learning in Neurology","volume":"30 6","pages":"1582-1583"},"PeriodicalIF":0.0,"publicationDate":"2024-12-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142774670","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}
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