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Molecular Psychiatry Oct 2023Dementia is a leading cause of disability and death worldwide. At present there is no disease modifying treatment for any of the most common types of dementia such as... (Review)
Review
Dementia is a leading cause of disability and death worldwide. At present there is no disease modifying treatment for any of the most common types of dementia such as Alzheimer's disease (AD), Vascular dementia, Lewy Body Dementia (LBD) and Frontotemporal dementia (FTD). Early and accurate diagnosis of dementia subtype is critical to improving clinical care and developing better treatments. Structural and molecular imaging has contributed to a better understanding of the pathophysiology of neurodegenerative dementias and is increasingly being adopted into clinical practice for early and accurate diagnosis. In this review we summarise the contribution imaging has made with particular focus on multimodal magnetic resonance imaging (MRI) and positron emission tomography imaging (PET). Structural MRI is widely used in clinical practice and can help exclude reversible causes of memory problems but has relatively low sensitivity for the early and differential diagnosis of dementia subtypes. F-fluorodeoxyglucose PET has high sensitivity and specificity for AD and FTD, while PET with ligands for amyloid and tau can improve the differential diagnosis of AD and non-AD dementias, including recognition at prodromal stages. Dopaminergic imaging can assist with the diagnosis of LBD. The lack of a validated tracer for α-synuclein or TAR DNA-binding protein 43 (TDP-43) imaging remain notable gaps, though work is ongoing. Emerging PET tracers such as C-UCB-J for synaptic imaging may be sensitive early markers but overall larger longitudinal multi-centre cross diagnostic imaging studies are needed.
Topics: Humans; Frontotemporal Dementia; Diagnosis, Differential; Alzheimer Disease; Lewy Body Disease; Neuroimaging; Positron-Emission Tomography
PubMed: 37608222
DOI: 10.1038/s41380-023-02215-8 -
FP Essentials Nov 2023Dementia, also called major neurocognitive disorder, is characterized by a chronic progressive loss of cognitive function in the absence of fluctuating consciousness. It...
Dementia, also called major neurocognitive disorder, is characterized by a chronic progressive loss of cognitive function in the absence of fluctuating consciousness. It represents a primarily geriatric syndrome that may be caused by one of several underlying conditions. There is insufficient evidence to support universal screening for cognitive impairment in older adults; however, clinicians should be alert to patient and caregiver concerns about cognitive changes and investigate such concerns with validated cognitive assessment tools. Alzheimer disease is the leading cause and prototypical form of dementia, presenting insidiously and causing progressive cognitive impairment with increasing severity over a period of years. Vascular dementia is the second most common form of dementia and often co-occurs with other progressive cognitive disorders. Lewy body dementias encompass Parkinson disease dementia and dementia with Lewy bodies, which have similar features and are differentiated primarily by the order of motor and cognitive symptom onset. Frontotemporal dementias occur earlier than other forms of dementia, progress rapidly, and often have a genetic component. An understanding of the conditions that cause dementia will assist clinicians in making an accurate diagnosis and providing appropriate treatment recommendations and counseling regarding the diagnosis and prognosis.
Topics: Humans; Aged; Dementia; Parkinson Disease; Lewy Body Disease; Alzheimer Disease
PubMed: 37976169
DOI: No ID Found -
Journal of Neurology, Neurosurgery, and... Jun 2022This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's disease (AD), Lewy body dementia...
OBJECTIVES
This longitudinal study compared emerging plasma biomarkers for neurodegenerative disease between controls, patients with Alzheimer's disease (AD), Lewy body dementia (LBD), frontotemporal dementia (FTD) and progressive supranuclear palsy (PSP).
METHODS
Plasma phosphorylated tau at threonine-181 (p-tau181), amyloid beta (Αβ)42, Aβ40, neurofilament light (NfL) and glial fibrillar acidic protein (GFAP) were measured using highly sensitive single molecule immunoassays (Simoa) in a multicentre cohort of 300 participants (controls=73, amyloid positive mild cognitive impairment (MCI+) and AD dementia=63, LBD=117, FTD=28, PSP=19). LBD participants had known positron emission tomography (PET)-Aβ status.
RESULTS
P-tau181 was elevated in MCI+AD compared with all other groups. Aβ42/40 was lower in MCI+AD compared with controls and FTD. NfL was elevated in all dementias compared with controls while GFAP was elevated in MCI+AD and LBD. Plasma biomarkers could classify between MCI+AD and controls, FTD and PSP with high accuracy but showed limited ability in differentiating MCI+AD from LBD. No differences were detected in the levels of plasma biomarkers when comparing PET-Aβ positive and negative LBD. P-tau181, NfL and GFAP were associated with baseline and longitudinal cognitive decline in a disease specific pattern.
CONCLUSION
This large study shows the role of plasma biomarkers in differentiating patients with different dementias, and at monitoring longitudinal change. We confirm that p-tau181 is elevated in MCI+AD, versus controls, FTD and PSP, but is less accurate in the classification between MCI+AD and LBD or detecting amyloid brain pathology in LBD. NfL was elevated in all dementia groups, while GFAP was elevated in MCI+AD and LBD.
Topics: Alzheimer Disease; Amyloid beta-Peptides; Biomarkers; Cognitive Dysfunction; Frontotemporal Dementia; Glial Fibrillary Acidic Protein; Humans; Lewy Body Disease; Longitudinal Studies; Neurodegenerative Diseases; Supranuclear Palsy, Progressive; tau Proteins
PubMed: 35078917
DOI: 10.1136/jnnp-2021-327788 -
Journal of Neurology, Neurosurgery, and... Nov 2019Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer's disease. The mechanisms by which trauma can trigger neurodegeneration are... (Review)
Review
Traumatic brain injury (TBI) leads to increased rates of dementia, including Alzheimer's disease. The mechanisms by which trauma can trigger neurodegeneration are increasingly understood. For example, diffuse axonal injury is implicated in disrupting microtubule function, providing the potential context for pathologies of tau and amyloid to develop. The neuropathology of post-traumatic dementias is increasingly well characterised, with recent work focusing on chronic traumatic encephalopathy (CTE). However, clinical diagnosis of post-traumatic dementia is problematic. It is often difficult to disentangle the direct effects of TBI from those produced by progressive neurodegeneration or other post-traumatic sequelae such as psychiatric impairment. CTE can only be confidently identified at postmortem and patients are often confused and anxious about the most likely cause of their post-traumatic problems. A new approach to the assessment of the long-term effects of TBI is needed. Accurate methods are available for the investigation of other neurodegenerative conditions. These should be systematically employed in TBI. MRI and positron emission tomography neuroimaging provide biomarkers of neurodegeneration which may be of particular use in the postinjury setting. Brain atrophy is a key measure of disease progression and can be used to accurately quantify neuronal loss. Fluid biomarkers such as neurofilament light can complement neuroimaging, representing sensitive potential methods to track neurodegenerative processes that develop after TBI. These biomarkers could characterise endophenotypes associated with distinct types of post-traumatic neurodegeneration. In addition, they might profitably be used in clinical trials of neuroprotective and disease-modifying treatments, improving trial design by providing precise and sensitive measures of neuronal loss.
Topics: Biomarkers; Brain; Brain Injuries, Traumatic; Chronic Traumatic Encephalopathy; Clinical Trials as Topic; Dementia; Disease Progression; Humans; Nerve Degeneration
PubMed: 31542723
DOI: 10.1136/jnnp-2017-317557 -
Journal of Music Therapy Oct 2023The number of people living with Alzheimer's disease and related dementias (ADRD) is growing proportional to our aging population. Although music-based interventions may... (Randomized Controlled Trial)
Randomized Controlled Trial
The number of people living with Alzheimer's disease and related dementias (ADRD) is growing proportional to our aging population. Although music-based interventions may offer meaningful support to these individuals, most music therapy research lacks well-matched comparison conditions and specific intervention focus, which limits evaluation of intervention effectiveness and possible mechanisms. Here, we report a randomized clinical crossover trial in which we examined the impact of a singing-based music therapy intervention on feelings, emotions, and social engagement in 32 care facility residents with ADRD (aged 65-97 years), relative to an analogous nonmusic condition (verbal discussion). Both conditions were informed by the Clinical Practice Model for Persons with Dementia and occurred in a small group format, three times per week for two weeks (six 25-minute sessions), with a two-week washout at crossover. We followed National Institutes of Health Behavior Change Consortium strategies to enhance methodological rigor. We predicted that music therapy would improve feelings, positive emotions, and social engagement, significantly more so than the comparison condition. We used a linear mixed model approach to analysis. In support of our hypotheses, the music therapy intervention yielded significant positive effects on feelings, emotions, and social engagement, particularly for those with moderate dementia. Our study contributes empirical support for the use of music therapy to improve psychosocial well-being in this population. Results also highlight the importance of considering patient characteristics in intervention design and offer practical implications for music selection and implementation within interventions for persons with ADRD.
Topics: Aged; Humans; Cross-Over Studies; Dementia; Emotions; Music; Music Therapy; Quality of Life; Singing; Aged, 80 and over
PubMed: 37220880
DOI: 10.1093/jmt/thad015 -
Nature Aging May 2023The increasing number of people with dementia globally illustrates the urgent need to reduce dementia's scale and impact. Lifetime social participation may affect... (Review)
Review
The increasing number of people with dementia globally illustrates the urgent need to reduce dementia's scale and impact. Lifetime social participation may affect dementia risk by increasing cognitive reserve, and through brain maintenance by reducing stress and improving cerebrovascular health. It may therefore have important implications for individual behavior and public health policy aimed at reducing dementia burden. Observational study evidence indicates that greater social participation in midlife and late life is associated with 30-50% lower subsequent dementia risk, although some of this may not be causal. Social participation interventions have led to improved cognition but, partly due to short follow-up and small numbers of participants, no reduction in risk of dementia. We summarize the evidence linking social participation with dementia, discuss potential mechanisms by which social participation is likely to reduce and mitigate the impact of neuropathology in the brain, and consider the implications for future clinical and policy dementia prevention interventions.
Topics: Humans; Dementia; Social Participation; Brain; Cognition; Cognitive Reserve; Observational Studies as Topic
PubMed: 37202513
DOI: 10.1038/s43587-023-00387-0 -
Neuropharmacology May 2020Molecular genetics has been an invaluable tool to help understand the molecular basis of neurodegenerative dementias. In this review, we provide an overview of the... (Review)
Review
Molecular genetics has been an invaluable tool to help understand the molecular basis of neurodegenerative dementias. In this review, we provide an overview of the genetic architecture underlying some of the most prevalent causes of dementia, including Alzheimer's dementia, frontotemporal lobar degeneration, Lewy body dementia, and prion diseases. We also discuss the complexity of the human genome and how the novel technologies have revolutionized and accelerated the way we screen the variety of our DNA. Finally, we also provide some examples about how this genetic knowledge is being transferred into the clinic through personalized medicine. This article is part of the special issue entitled 'The Quest for Disease-Modifying Therapies for Neurodegenerative Disorders'.
Topics: Alzheimer Disease; Animals; Dementia; Frontotemporal Lobar Degeneration; Genetic Testing; Humans; Lewy Body Disease; Neurodegenerative Diseases; Pharmacogenetics; Prion Diseases
PubMed: 32097768
DOI: 10.1016/j.neuropharm.2020.108014 -
Journal of Neurochemistry Jul 2021Long-term or severe lack of protective factors is important in the pathogenesis of neurodegenerative dementia. Progranulin (PGRN), a neurotrophic factor expressed mainly... (Review)
Review
Long-term or severe lack of protective factors is important in the pathogenesis of neurodegenerative dementia. Progranulin (PGRN), a neurotrophic factor expressed mainly in neurons and microglia, has various neuroprotective effects such as anti-inflammatory effects, promoting neuron survival and neurite growth, and participating in normal lysosomal function. Mutations in the PGRN gene (GRN) have been found in several neurodegenerative dementias, including frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD). Herein, PGRN deficiency and PGRN hydrolytic products (GRNs) in the pathological changes related to dementia, including aggregation of tau and TAR DNA-binding protein 43 (TDP-43), amyloid-β (Aβ) overproduction, neuroinflammation, lysosomal dysfunction, neuronal death, and synaptic deficit have been summarized. Furthermore, as some therapeutic strategies targeting PGRN have been developed in various models, we highlighted PGRN as a potential anti-neurodegeneration target in dementia.
Topics: Alzheimer Disease; Animals; Dementia; Frontotemporal Lobar Degeneration; Humans; Neurodegenerative Diseases; Progranulins
PubMed: 33930186
DOI: 10.1111/jnc.15378 -
Neurologic Clinics Feb 2020Neuroimaging provides a window on the biological events underlying dementia. Amyloid PET is positive in Alzheimer disease (AD) and some cases of diffuse Lewy body... (Review)
Review
Neuroimaging provides a window on the biological events underlying dementia. Amyloid PET is positive in Alzheimer disease (AD) and some cases of diffuse Lewy body disease, but negative in the frontotemporal dementias (FTDs). Tau PET using the current tracers shows the greatest signal in AD and a lesser signal in FTD. Quantifying volume loss with MRI and measuring metabolism with fluorodeoxyglucose PET helps separate different causes of dementia and follow their progression. Brain inflammation can be assessed with PET. Some of these techniques, still investigational, are likely to find their clinical niche in the near future.
Topics: Alzheimer Disease; Dementia; Disease Progression; Frontotemporal Dementia; Humans; Lewy Body Disease; Magnetic Resonance Imaging; Neuroimaging; Positron-Emission Tomography; tau Proteins
PubMed: 31761062
DOI: 10.1016/j.ncl.2019.08.003 -
Canadian Journal on Aging = La Revue... Sep 2019ABSTRACTThe prevention and management of dementia in Canada is at a crossroads. Despite the low diagnosis rates, the number of persons living with dementia continues to... (Review)
Review
ABSTRACTThe prevention and management of dementia in Canada is at a crossroads. Despite the low diagnosis rates, the number of persons living with dementia continues to increase. Yet, Canada's health care policies have resulted in more people living with dementia living at home, and with most of their care being provided by family, friends, and significant others. This Policy Note provides an overview of a joint submission from the Canadian Gerontological Nursing Association (CGNA) and the Registered Nurses' Association of Ontario (RNAO) to the Standing Senate Committee on Social Affairs, Science, and Technology. This article outlines the background and recommendations in five key areas of dementia care in Canada: health system resources, education and training of health providers, housing, care partners, and the integration of health and social supports. Based on these five key areas, a number of health and social policy interventions are discussed.
Topics: Aged; Canada; Caregivers; Dementia; Education, Nursing; Geriatrics; Health Policy; Humans
PubMed: 31385569
DOI: 10.1017/S071498081800065X