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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 -
Age (Dordrecht, Netherlands) Feb 2016Serum uric acid (sUA) level may be associated with cognitive impairment/dementia. It is possible this relationship varies with dementia subtype, particularly between... (Meta-Analysis)
Meta-Analysis Review
Serum uric acid (sUA) level may be associated with cognitive impairment/dementia. It is possible this relationship varies with dementia subtype, particularly between vascular dementias (VaD) and Alzheimer's (AD) or Parkinson's disease (PDD)-related dementia. We aimed to present a synthesis of all published data on sUA and relationship with dementia/cognition through systematic review and meta-analysis. We included studies that assessed the association between sUA and any measure of cognitive function or a clinical diagnosis of dementia. We pre-defined subgroup analyses for patients with AD, VaD, PDD, mild cognitive impairment (MCI), and mixed or undifferentiated. We assessed risk of bias/generalizability, and where data allowed, we performed meta-analysis to describe pooled measures of association across studies. From 4811 titles, 46 papers (n = 16,688 participants) met our selection criteria. Compared to controls, sUA was lower in dementia (SDM -0.33 (95%CI)). There were differences in association by dementia type with apparent association for AD (SDM -0.33 (95%CI)) and PDD (SDM -0.67 (95%CI)) but not in cases of mixed dementia (SDM 0.19 (95%CI)) or VaD (SDM -0.05 (95%CI)). There was no correlation between scores on Mini-Mental State Examination and sUA level (summary r 0.08, p = 0.27), except in patients with PDD (r 0.16, p = 0.003). Our conclusions are limited by clinical heterogeneity and risk of bias in studies. Accepting this caveat, the relationship between sUA and dementia/cognitive impairment is not consistent across all dementia groups and in particular may differ in patients with VaD compared to other dementia subtypes.
Topics: Aging; Cognition; Cognitive Dysfunction; Dementia; Disease Progression; Humans; Neuropsychological Tests; Uric Acid
PubMed: 26820749
DOI: 10.1007/s11357-016-9871-8 -
Journal of Alzheimer's Disease : JAD 2021Self-reported discrimination is a source of psychosocial stress that has been previously associated with poor cognitive function in older African Americans without...
BACKGROUND
Self-reported discrimination is a source of psychosocial stress that has been previously associated with poor cognitive function in older African Americans without dementia.
OBJECTIVE
Here, we examine the association of discrimination with dementia and cognitive impairment in racially diverse older Brazilians.
METHODS
We included 899 participants 65 years or older (34.3% Black) from the Pathology, Alzheimer's and Related Dementias Study (PARDoS), a community-based study of aging and dementia. A structured interview with informants of the deceased was conducted. The interview included the Clinical Dementia Rating (CDR) Scale for the diagnosis of dementia and cognitive impairment proximate to death and the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) as a second measure of cognitive impairment. Informant-reported discrimination was assessed using modified items from the Major and Everyday Discrimination Scales.
RESULTS
Discrimination was reported by informants of 182 (20.2%) decedents and was more likely reported by informants of Blacks than Whites (25.3% versus 17.6%, p = 0.006). Using the CDR, a higher level of informant-reported discrimination was associated with higher odds of dementia (OR: 1.24, 95% CI 1.08 -1.42, p = 0.002) and cognitive impairment (OR: 1.21, 95% CI: 1.06 -1.39, p = 0.004). Similar results were observed using the IQCODE (estimate: 0.07, SE: 0.02, p = 0.003). The effects were independent of race, sex, education, socioeconomic status, major depression, neuroticism, or comorbidities.
CONCLUSION
Higher level of informant-reported discrimination was associated with higher odds of dementia and cognitive impairment in racially diverse older Brazilians.
Topics: Aged; Aged, 80 and over; Brazil; Cognitive Dysfunction; Dementia; Family; Female; Humans; Interviews as Topic; Male; Mental Status and Dementia Tests; Social Discrimination; Stress, Psychological
PubMed: 33935076
DOI: 10.3233/JAD-201436 -
Journal of Alzheimer's Disease : JAD 2023Several clinical trials have examined diet and physical activity lifestyle changes as mitigation strategies for risk factors linked to cognitive decline and dementias...
A Mediterranean Diet and Walking Intervention to Reduce Cognitive Decline and Dementia Risk in Independently Living Older Australians: The MedWalk Randomized Controlled Trial Experimental Protocol, Including COVID-19 Related Modifications and Baseline Characteristics.
BACKGROUND
Several clinical trials have examined diet and physical activity lifestyle changes as mitigation strategies for risk factors linked to cognitive decline and dementias such as Alzheimer's disease. However, the ability to modify these behaviors longer term, to impact cognitive health has remained elusive.
OBJECTIVE
The MedWalk trial's primary aim is to investigate whether longer-term adherence to a Mediterranean-style diet and regular walking, delivered through motivational interviewing and cognitive-behavioral therapy (MI-CBT), can reduce age-associated cognitive decline and other dementia risk factors in older, independently living individuals without cognitive impairment.
METHODS
MedWalk, a one-year cluster-randomized controlled trial across two Australian states, recruited 60-90-year-old people from independent living retirement villages and the wider community. Participants were assigned to either the MedWalk intervention or a control group (maintaining their usual diet and physical activity). The primary outcome is 12-month change in visual memory and learning assessed from errors on the Paired Associates Learning Task of the Cambridge Neuropsychological Test Automated Battery. Secondary outcomes include cognition, mood, cardiovascular function, biomarkers related to nutrient status and cognitive decline, MI-CBT effectiveness, Mediterranean diet adherence, physical activity, quality of life, cost-effectiveness, and health economic evaluation.Progress and Discussion:Although COVID-19 impacts over two years necessitated a reduced timeline and sample size, MedWalk retains sufficient power to address its aims and hypotheses. Baseline testing has been completed with 157 participants, who will be followed over 12 months. If successful, MedWalk will inform interventions that could substantially reduce dementia incidence and ameliorate cognitive decline in the community.
TRIAL REGISTRATION
Registered on the Australia New Zealand Clinical Trials Registry ANZCTR 12620000978965 (https://www.anzctr.org.au).
Topics: Humans; Aged; Aged, 80 and over; Diet, Mediterranean; Quality of Life; Australia; COVID-19; Cognitive Dysfunction; Walking; Cognition; Dementia; Randomized Controlled Trials as Topic
PubMed: 37781806
DOI: 10.3233/JAD-230641 -
The Gerontologist Nov 2019Cognitive impairment and dementia continue to threaten the aging population. Although no one is immune, certain groups, namely black older persons, are more likely to... (Review)
Review
Cognitive impairment and dementia continue to threaten the aging population. Although no one is immune, certain groups, namely black older persons, are more likely to have a diagnosis of certain dementias. Because researchers have not found a purely biological reason for this disparity, they have turned to a biopsychosocial model. Specifically, black persons in the United States are more likely to live with social conditions that affect their stress levels which in turn affect physiological regulation leading to conditions that result in higher levels of cognitive impairment or dementia. Here we discuss some of these social conditions such as discrimination, education, and socioeconomic status, and how physiological dysregulation, namely allostatic load that can lead to cognitive impairment and dementia in black persons especially.
Topics: Black or African American; Allostasis; Cognitive Dysfunction; Dementia; Humans; Minority Groups; Racism; Socioeconomic Factors; Stress, Psychological; United States
PubMed: 30169640
DOI: 10.1093/geront/gny104 -
Journal of Pain and Symptom Management May 2022Pain is a significant concern among older adults with Alzheimer's disease and related dementias (ADRD).
CONTEXT
Pain is a significant concern among older adults with Alzheimer's disease and related dementias (ADRD).
OBJECTIVES
Examine the association between cognitive impairment across the ADRD spectrum and pain assessment and treatment in community-dwelling older Americans.
METHODS
This cross-sectional, population-based study included 16,836 community-dwelling participants ≥ 50 years in the 2018 Health and Retirement Study. ADRD, assessed by validated cognitive measures, was categorized into "dementia," "cognitive impairment, no dementia (CIND)" and "intact cognition." Pain assessment included pain presence (often being troubled with pain), pain severity (degree of pain most of the time [mild/moderate/severe]), and pain interference (pain making it difficult to do usual activities). Pain treatment included recent use of over-the-counter pain medications and opioids (past 3 months), and regular intake of prescriptions for pain.
RESULTS
Dementia were associated with lower likelihood of reporting pain presence (Odds Ratio [OR]= 0.61, P = 0.01), pain interference (OR = 0.46, P < 0.001), reporting lower pain severity (e.g., moderate vs. no: Relative Risk Ratio = 0.38, P < 0.001), and lower likelihood of receiving pain treatment, that is, recent use of over-the-counter pain medications (OR = 0.60, P = 0.02) and opioids (OR = 0.33, P < 0.001), and regular intake of prescriptions for pain (OR = 0.461, P = 0.002). CIND was associated with reporting lower pain severity (e.g., moderate vs. no: Relative Risk Ratio = 0.75, P = 0.021), lower likelihood of reporting pain interference (OR = 0.79, P = 0.045) and recent over-the-counter pain medication use (OR = 0.74, P = 0.026).
CONCLUSION
CIND and dementia increased the risk of under-report and under-treatment of pain. Systematic efforts are needed to improve pain recognition and treatment among older adults with cognitive impairment, regardless of dementia diagnosis.
Topics: Aged; Alzheimer Disease; Analgesics, Opioid; Cognitive Dysfunction; Cross-Sectional Studies; Dementia; Humans; Independent Living; Pain; United States
PubMed: 35081442
DOI: 10.1016/j.jpainsymman.2022.01.012 -
Journal of Alzheimer's Disease : JAD 2023Despite the high burden of Alzheimer's disease and other dementias among the Hispanic population worldwide, little is known about how dementia affects healthcare...
BACKGROUND
Despite the high burden of Alzheimer's disease and other dementias among the Hispanic population worldwide, little is known about how dementia affects healthcare utilizations among this population outside of the US, in particular among those in the Caribbean region.
OBJECTIVE
This study examines healthcare utilization associated with Alzheimer's disease and other dementias among older adults in the Caribbean as compared to the US.
METHODS
We conducted harmonized analyses of two population-based surveys, the 10/66 Dementia Group Research data collected in Dominican Republic, Cuba, and Puerto Rico, and the US-based Health and Retirement Study. We examined changes in hospital nights and physician visits in response to incident and ongoing dementias.
RESULTS
Incident dementia significantly increased the risk of hospitalization and number of hospital nights in both populations. Ongoing dementia increased the risk of hospitalization and hospital nights in the US, with imprecise estimates for the Caribbean. The number of physician visits was elevated in the US but not in the Caribbean.
CONCLUSIONS
The concentration of increased healthcare utilization on hospital care and among patients with incident dementia suggests an opportunity for improved outpatient management of new and existing dementia patients in the Caribbean.
Topics: United States; Humans; Aged; Alzheimer Disease; Delivery of Health Care; Patient Acceptance of Health Care; Puerto Rico; Ethnicity
PubMed: 37840491
DOI: 10.3233/JAD-230505 -
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 -
NeuroImage. Clinical 2022Lateral ventricles are reliable and sensitive indicators of brain atrophy and disease progression in behavioral variant frontotemporal dementia (bvFTD). We aimed to...
INTRODUCTION
Lateral ventricles are reliable and sensitive indicators of brain atrophy and disease progression in behavioral variant frontotemporal dementia (bvFTD). We aimed to investigate whether an automated tool using ventricular features could improve diagnostic accuracy in bvFTD across neurodegenerative diseases.
METHODS
Using 678 subjects -69 bvFTD, 38 semantic variant, 37 primary non-fluent aphasia, 218 amyloid + mild cognitive impairment, 74 amyloid + Alzheimer's Dementia and 242 normal controls- with a total of 2750 timepoints, lateral ventricles were segmented and differences in ventricular features were assessed between bvFTD, normal controls and other dementia cohorts.
RESULTS
Ventricular antero-posterior ratio (APR) was the only feature that was significantly different and increased faster in bvFTD compared to all other cohorts. We achieved a 10-fold cross-validation accuracy of 80% (77% sensitivity, 82% specificity) in differentiating bvFTD from all other cohorts with other ventricular features (i.e., total ventricular volume and left-right lateral ventricle ratios), and 76% accuracy using only the single APR feature.
DISCUSSION
Ventricular features, particularly the APR, might be reliable and easy-to-implement markers for bvFTD diagnosis. We have made our ventricle feature estimation and bvFTD diagnostic tool publicly available, allowing application of our model in other studies.
Topics: Alzheimer Disease; Atrophy; Cognitive Dysfunction; Disease Progression; Frontotemporal Dementia; Humans; Magnetic Resonance Imaging
PubMed: 35134704
DOI: 10.1016/j.nicl.2022.102947