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Advances in Pharmacology (San Diego,... 2018Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in... (Review)
Review
Neuroinflammation has long been considered a potential contributor to neurodegenerative disorders that result in dementia. Accumulation of abnormal protein aggregates in Alzheimer's disease, frontotemporal dementia, and dementia with Lewy bodies is associated with the activation of microglia and astrocytes into proinflammatory states, and chronic low-level activation of glial cells likely contributes to the pathological changes observed in these and other neurodegenerative diseases. The 18kDa translocator protein (TSPO) is a key biomarker for measuring inflammation in the brain via positron emission tomography (PET). Increased TSPO density has been observed in brain tissue from patients with neurodegenerative diseases and colocalizes to activated microglia and reactive astrocytes. Several radioligands have been developed to measure TSPO density in vivo with PET, and these have been used in clinical studies of different dementia syndromes. However, TSPO radioligands have limitations, including low specific-to-nonspecific signal and differential affinity to a polymorphism on the TSPO gene, which must be taken into consideration in designing and interpreting human PET studies. Nonetheless, most PET studies have shown that increased TSPO binding is associated with various dementias, suggesting that TSPO has potential as a biomarker to further explore the role of neuroinflammation in dementia pathogenesis and may prove useful in monitoring disease progression.
Topics: Biomarkers; Dementia; Disease Progression; Humans; Inflammation; Nervous System; Receptors, GABA
PubMed: 29413519
DOI: 10.1016/bs.apha.2017.08.004 -
The Lancet. Healthy Longevity Aug 2021People with dementia die prematurely. Identifying differences in mortality rates between different types of dementia might aid in the development of preventive... (Meta-Analysis)
Meta-Analysis
BACKGROUND
People with dementia die prematurely. Identifying differences in mortality rates between different types of dementia might aid in the development of preventive interventions for the most vulnerable populations. The aim of this study was to compare the difference in mortality rates between individuals without dementia and individuals with various types of dementia.
METHODS
For this systematic review and meta-analysis, we did a systematic search of MEDLINE, PubMed, Embase, and Cochrane Library from inception to July 11, 2020, for cross-sectional or cohort studies that assessed mortality and survival-related outcomes among people with different types of dementia compared with people without dementia. Single-arm studies without comparison groups and autopsy studies or family studies that used a selected sample were excluded. The Newcastle-Ottawa Scale was used by two authors (D-JL and C-SC) independently to measure the methodological quality of included studies, and two authors (F-CY and P-TT) independently extracted data. We assessed differences in all-cause mortality rate and survival time from dementia diagnosis between individuals without dementia, individuals with Alzheimer's disease, and individuals with non-Alzheimer's disease dementias. The secondary outcomes were age at death and survival time from disease onset. Random-effects meta-analyses were done. Effect sizes included hazard ratios (HRs) and mean differences (MDs) with 95% CIs. Potential moderators, including age-associated moderators, were identified through meta-regression and subgroup analyses. This study is registered with PROSPERO, CRD42020198786.
FINDINGS
Our database search identified 11 973 records, and we included 78 eligible studies in our analyses, encompassing 63 125 individuals with dementia and 152 353 controls. Individuals with any type of dementia had a higher mortality rate than individuals without dementia (HR 5·90, 95% CI 3·53 to 9·86), and the HR for all-cause mortality was highest for Lewy body dementia (17·88, 5·87 to 54·46). After diagnosis, the mean survival time for people with Alzheimer's disease was 5·8 years (SD 2·0). Compared with people with Alzheimer's disease, a diagnosis of any non-Alzheimer's disease dementia was associated with a higher risk of all-cause mortality (HR 1·33, 1·21 to 1·46), a shorter survival time from diagnosis (MD -1·12 years, 95% CI -1·52 to -0·72), and a younger age at death (-1·76 years, -2·66 to -0·85). Survival time from disease onset was also shorter in people with non-Alzheimer's dementia, across types, compared with people with Alzheimer's disease, but the subgroup analysis revealed that this difference was only significant for vascular dementia (MD -1·27 years, -1·90 to -0·65) and dementia with Lewy bodies (MD -1·06 years, -1·68 to -0·44). The interactions between age and several survival-related outcomes were significant. 39 (50%) of the 78 included studies were rated as good quality, and large heterogeneity (I>75%) was observed for most of the study outcomes.
INTERPRETATION
Alzheimer's disease is the most common type of dementia and one of the major causes of mortality worldwide. However, the findings from the current study suggest that non-Alzheimer's disease dementias were associated with higher morality rates and shorter life expectancy than Alzheimer's disease. Developing tailored treatment and rehabilitation programmes for different types of dementia is important for mental health providers, patients, and their families.
FUNDING
None.
Topics: Alzheimer Disease; Cross-Sectional Studies; Dementia; Dementia, Vascular; Humans; Lewy Body Disease
PubMed: 36097997
DOI: 10.1016/S2666-7568(21)00140-9 -
Cleveland Clinic Journal of Medicine Apr 2014Dementia is commonly encountered in the elderly, with prevalence increasing with age. Although Alzheimer disease is the most recognized form of dementia, other types... (Review)
Review
Dementia is commonly encountered in the elderly, with prevalence increasing with age. Although Alzheimer disease is the most recognized form of dementia, other types have distinct clinical features and are often overlooked. Proper identification aids patients, caregivers, and physicians in planning and management.
Topics: Aging; Brain; Brain Diseases; Dementia; Diagnosis, Differential; Diagnostic Imaging; Humans; Neurodegenerative Diseases
PubMed: 24692443
DOI: 10.3949/ccjm.81a.13068 -
Journal of Communication Disorders 2010There are many distinct forms of dementia whose pharmacological and behavioral management differ. Differential diagnosis among the dementia variants currently relies... (Review)
Review
UNLABELLED
There are many distinct forms of dementia whose pharmacological and behavioral management differ. Differential diagnosis among the dementia variants currently relies upon a weighted combination of genetic and protein biomarkers, neuroanatomical integrity, and behavior. Diagnostic specificity is complicated by a high degree of overlap in the initial presenting symptoms across dementia subtypes. For this reason, reliable markers are of considerable diagnostic value. Communication disorders have proven to be among the strongest predictors for discriminating among dementia subtypes. As such, speech-language pathologists may be poised to make an increasingly visible contribution to dementia diagnosis and its ongoing management. The value and durability of this potential contribution, however, demands an improved discipline-wide knowledge base about the unique features associated with different dementia variants. To this end we provide an overview of cognition, language, and clinical pathological features of four of the most common non-Alzheimer's dementias: frontotemporal dementia, vascular dementia, Lewy body disease dementia, and Parkinson's disease dementia.
LEARNING OUTCOMES
Readers will learn characteristics and distinguishing features of several non-Alzheimer's dementias, including Parkinson's disease dementia, frontotemporal dementia, vascular dementia, and Lewy body dementia. Readers will also learn to distinguish between several variants of frontotemporal dementia. Finally, readers will gain knowledge of the term primary progressive aphasia as it relates to the aforementioned dementia etiologies.
Topics: Aphasia; Cognition Disorders; Dementia; Disease Progression; Humans; Language Disorders; Parkinson Disease; Semantics; Speech Disorders
PubMed: 20493496
DOI: 10.1016/j.jcomdis.2010.04.011 -
Neurobiology of Disease Nov 2020Causative genes involved in familial forms of dementias, including Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies... (Review)
Review
Causative genes involved in familial forms of dementias, including Alzheimer's disease (AD), frontotemporal lobar degeneration (FTLD) and dementia with Lewy bodies (DLB), as well as amyotrophic lateral sclerosis and prion diseases where dementia is present as a significant clinical feature, are associated with distinct proteinopathies. This review summarizes the relationship between known genetic determinants of these dementia syndromes and variations in key neuropathological proteins in terms of three types of heterogeneity: (i) Locus Heterogeneity, whereby mutations in different genes cause a similar proteinopathy, as exemplified by mutations in APP, PSEN1 and PSEN2 leading to AD neuropathology; (ii) Allelic Heterogeneity, whereby different mutations in the same gene lead to different proteinopathies or neuropathological severity, as exemplified by different mutations in MAPT and PRNP giving rise to protein species that differ in their biochemistry and affected cell types; and (iii) Phenotypic Heterogeneity, where identical gene mutations lead to different proteinopathies, as exemplified by LRRK2 p.G2019S being associated with variable Lewy body presence and alternative AD neuropathology or FTLD-tau. Of note, the perceived homogeneity in histologic phenotypes may arise from laboratory-specific assessment protocols which can differ in the panel of proteins screened. Finally, the understanding of the complex relationship between genotype and phenotype in dementia families is highly relevant in terms of therapeutic strategies which range from targeting specific genes, to a broader strategy of targeting a downstream, common biochemical problem that leads to the histopathology.
Topics: Dementia; Genetic Association Studies; Humans
PubMed: 32927063
DOI: 10.1016/j.nbd.2020.105082 -
Annals of Neurology Jul 2008In contrast with more common dementing conditions that typically develop over years, rapidly progressive dementias can develop subacutely over months, weeks, or even... (Review)
Review
In contrast with more common dementing conditions that typically develop over years, rapidly progressive dementias can develop subacutely over months, weeks, or even days and be quickly fatal. Because many rapidly progressive dementias are treatable, it is paramount to evaluate and diagnose these patients quickly. This review summarizes recent advances in the understanding of the major categories of RPD and outlines efficient approaches to the diagnosis of the various neurodegenerative, toxic-metabolic, infectious, autoimmune, neoplastic, and other conditions that may progress rapidly.
Topics: Autoimmune Diseases; Brain; Dementia; Diagnosis, Differential; Disease Progression; Early Diagnosis; Encephalitis; Humans; Neurodegenerative Diseases; Paraneoplastic Syndromes, Nervous System; Prion Diseases; Time Factors
PubMed: 18668637
DOI: 10.1002/ana.21430 -
Alzheimer Disease and Associated... 2011We compared patterns of neuropsychiatric symptoms across 4 dementia types [Alzheimer disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB), and... (Comparative Study)
Comparative Study Randomized Controlled Trial
We compared patterns of neuropsychiatric symptoms across 4 dementia types [Alzheimer disease (AD), vascular dementia (VAD), dementia with Lewy bodies (DLB), and Parkinson disease dementia], and 2 mixed groups (AD/VAD and AD/DLB) in sample of 2,963 individuals from the National Alzheimer's Coordinating Center Uniform Data Set between September 2005 and June 2008. We used confirmatory factor analysis to compare neuropsychiatric symptom severity ratings made by collateral sources on the Neuropsychiatric Inventory Questionnaire for people with Clinical Dementia Rating scores of 1 or higher. A 3-factor model of psychiatric symptoms (mood, psychotic, and frontal) was shared across all dementia types. Between-group comparisons revealed unique neuropsychiatric profiles by dementia type. The AD group had moderate levels of mood, psychotic, and frontal symptoms whereas VAD exhibited the highest levels and Parkinson disease dementia had the lowest levels. DLB and the mixed dementias had more complex symptom profiles. Depressed mood was the dominant symptom in people with mild diagnoses. Differing psychiatric symptom profiles provide useful information regarding the noncognitive symptoms of dementia.
Topics: Aged; Aged, 80 and over; Alzheimer Disease; Dementia; Dementia, Vascular; Female; Humans; Lewy Body Disease; Male; Middle Aged; Neuropsychological Tests; Parkinson Disease; Psychiatric Status Rating Scales
PubMed: 22086220
DOI: 10.1097/WAD.0b013e31820d89b6 -
The Western Journal of Medicine Jun 1987Dementia is an acquired impairment of intellect produced by brain dysfunction. In the past, dementia was regarded as inevitably chronic, progressive and irreversible....
Dementia is an acquired impairment of intellect produced by brain dysfunction. In the past, dementia was regarded as inevitably chronic, progressive and irreversible. More recently dementia has been viewed as a clinical syndrome that may be produced by both irreversible and reversible conditions. Recognition of the presence of a dementia syndrome should be followed by an evaluation for potentially treatable causes of the intellectual deterioration. Dementia treatment includes therapy for reversible or curable dementias and nonspecific interventions that may improve the condition of patients with progressive dementia syndromes.
Topics: Alzheimer Disease; Dementia; Humans
PubMed: 3617715
DOI: No ID Found -
International Journal of Geriatric... Apr 2023To compare survival and risk factors associated with mortality in common young-onset dementias (YOD) including Huntington's disease.
OBJECTIVES
To compare survival and risk factors associated with mortality in common young-onset dementias (YOD) including Huntington's disease.
METHODS
This retrospective cohort study included inpatients from an Australian specialist neuropsychiatry service, over 20 years. Dementia diagnoses were based on consensus criteria and Huntington's disease (HD) was confirmed genetically. Mortality and cause of death were determined using linkage to the Australian Institute of Health and Welfare National Death Index.
RESULTS
There were 386 individuals with YOD included. The dementia types included frontotemporal dementia (FTD) (24.5%), HD (21.2%) and Alzheimer's disease (AD) (20.5%). 63% (n = 243) individuals had died. The longest median survival was for those who had HD, 18.8 years from symptom onset and with a reduced mortality risk compared to AD and FTD (hazard ratio 0.5). Overall, people with YOD had significantly increased mortality, of 5-8 times, compared to the general population. Females with a YOD had higher standardised mortality ratio compared to males (9.3 vs. 4.9) overall. The most frequent cause of death in those with HD was reported as HD, with other causes of death in the other YOD-subtypes related to dementia and mental/behavioural disorders.
DISCUSSION
This is the first Australian study to investigate survival and risk factors of mortality in people with YOD. YOD has a significant risk of death compared to the general population. Our findings provide useful clinical information for people affected by YOD as well as future planning and service provision.
Topics: Male; Female; Humans; Huntington Disease; Frontotemporal Dementia; Retrospective Studies; Age of Onset; Australia; Alzheimer Disease
PubMed: 37062919
DOI: 10.1002/gps.5913 -
American Journal of Alzheimer's Disease... 2002Dementia and its associated diseases are important causes of disability and morbidity in developed countries, especially in the aged population. As the babyboomers... (Review)
Review
Dementia and its associated diseases are important causes of disability and morbidity in developed countries, especially in the aged population. As the babyboomers arrive at retirement and individuals over 100 are one of the fastest growing segments of our nation's population, we may realize the substantial cost these diseases bring to society. Dementia is characterized by a significant loss of cognitive function and should be clinically distinguished from an acute delirium or decreased arousal. Its manifestations cause anguish to millions of caregivers and family members, who are pressed to cope with their loved one's unfortunate decline in multiple cognitive domains, functioning, and behavior. Early detection and management may prevent overuse of costly medical resources and allow patients and family members time to prepare for future medical, financial, and emotional challenges. Diagnostic clues to the etiology of the patient's dementia can be found in a medical workup in which the neurologic history and examination (including mental status examination) are essential and neuroimaging is indicated. Herein, the concept of central nervous system (CNS) degenerative diseases as disorders of specific proteins is introduced. This review is intended to summarize clinical, biological, and genetic features of the common subtypes of dementia, and bring light to potential benefits of early and accurate diagnoses to optimize treatment. Details of the various diseases remain only partially uncovered, raising extensive prospects for future research and therapy for patients with dementia.
Topics: Alzheimer Disease; Brain; Dementia; Diagnosis, Differential; Humans; Nerve Tissue Proteins
PubMed: 11831415
DOI: 10.1177/153331750201700106