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Age and Ageing Aug 2023The PRomoting Activity, Independence and Stability in Early Dementia (PrAISED) study delivered an exercise and functional activity programme to participants living with... (Randomized Controlled Trial)
Randomized Controlled Trial
The facilitators and barriers to improving functional activity and wellbeing in people with dementia: a qualitative study from the process evaluation of Promoting Activity, Independence and Stability in Early Dementia (PrAISED).
BACKGROUND
The PRomoting Activity, Independence and Stability in Early Dementia (PrAISED) study delivered an exercise and functional activity programme to participants living with dementia. A Randomised Controlled Trial showed no measurable benefits in activities of daily living, physical activity or quality of life.
OBJECTIVE
To explore participants' responses to PrAISED and explain why an intervention that might be expected to have produced measurable health gains did not do so.
METHODS
A process evaluation using qualitative methods, comprising interviews and researcher notes.
SETTING
Data were collected in participants' homes or remotely by telephone or videoconferencing.
SAMPLE
A total of 88 interviews were conducted with 44 participants living with dementia (n = 32 intervention group; n = 12 control group) and 39 caregivers. A total of 69 interviews were conducted with 26 therapists.
RESULTS
Participants valued the intervention as proactively addressing health issues that were of concern to them, and as a source of social contact, interaction, information and advice. Facilitators to achieving positive outcomes included perceiving progress towards desired goals, positive expectations, therapists' skills and rapport with participants, and caregiver support. Barriers included: cognitive impairment, which prevented independent engagement and carry-over between sessions; chronic physical health problems and intercurrent acute illness and injury; 'tapering' (progressively infrequent supervision intended to help develop habits and independent activity); and the COVID-19 pandemic.
CONCLUSIONS
Self-directed interventions may not be appropriate in the context of dementia, even in the mild stages of the condition. Dementia-specific factors affected outcomes including caregiver support, rapport with therapists, availability of supervision, motivational factors and the limitations of remote delivery. The effects of cognitive impairment, multimorbidity and frailty overwhelmed any positive impact of the intervention. Maintenance of functional ability is valued, but in the face of inevitable progression of disease, other less tangible outcomes become important, challenging how we frame 'health gain' and trial outcomes.
Topics: Humans; Activities of Daily Living; COVID-19; Pandemics; Quality of Life; Dementia
PubMed: 37603841
DOI: 10.1093/ageing/afad166 -
Alzheimer's disease and its related dementias in US Native Americans: A major public health concern.Ageing Research Reviews Sep 2023Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD) are growing public health concerns in aged populations of all ethnic and racial groups. AD and ADRD are... (Review)
Review
Alzheimer's disease (AD) and Alzheimer's related dementias (ADRD) are growing public health concerns in aged populations of all ethnic and racial groups. AD and ADRD are caused by multiple factors, such as genetic mutations, modifiable and non-modifiable risk factors, and lifestyle. Studies of postmortem brains have revealed multiple cellular changes implicated in AD and ADRD, including the accumulation of amyloid beta and phosphorylated tau, synaptic damage, inflammatory responses, hormonal imbalance, mitochondrial abnormalities, and neuronal loss. These changes occur in both early-onset familial and late-onset sporadic forms. Two-thirds of women and one-third of men are at life time risk for AD. A small proportion of total AD cases are caused by genetic mutations in amyloid precursor protein, presenilin 1, and presenilin 1 genes, and the APOE4 allele is a risk factor. Tremendous research on AD/ADRD, and other comorbidities such as diabetes, obesity, hypertension, and cancer has been done on almost all ethnic groups, however, very little biomedical research done on US Native Americans. AD/ADRD prevalence is high among all ethnic groups. In addition, US Native Americans have poorer access to healthcare and medical services and are less likely to receive a diagnosis once they begin to exhibit symptoms, which presents difficulties in treating Alzheimer's and other dementias. One in five US Native American people who are 45 years of age or older report having memory issues. Further, the impact of caregivers and other healthcare aspects on US Native Americans is not yet. In the current article, we discuss the history of Native Americans of United States (US) and health disparities, occurrence, and prevalence of AD/ADRD, and shedding light on the culturally sensitive caregiving practices in US Native Americans. This article is the first to discuss biomedical research and healthcare disparities in US Native Americans with a focus on AD and ADRD, we also discuss why US Native Americans are reluctant to participate in biomedical research.
Topics: Aged; Female; Humans; Male; Alzheimer Disease; American Indian or Alaska Native; Amyloid beta-Peptides; Presenilin-1; Public Health; United States
PubMed: 37544432
DOI: 10.1016/j.arr.2023.102027 -
European Neuropsychopharmacology : the... Nov 2023Alzheimer's Disease (AD) is a currently incurable but increasingly prevalent fatal and progressive neurodegenerative disease, demanding consideration of therapeutically... (Review)
Review
Alzheimer's Disease (AD) is a currently incurable but increasingly prevalent fatal and progressive neurodegenerative disease, demanding consideration of therapeutically relevant natural products and their synthetic analogues. This paper reviews evidence for effectiveness of natural and synthetic psychedelics in the treatment of AD causes and symptoms. The plastogenic effects of serotonergic psychedelics illustrate that they have efficacy for addressing multiple facets of AD pathology. We review findings illustrating neuroplasticity mechanisms of classic (serotonergic) and non-classic psychedelics that indicate their potential as treatments for AD and related dementias. Classic psychedelics modulate glutamatergic neurotransmission and stimulate synaptic and network remodeling that facilitates synaptic, structural and behavioral plasticity. Up-regulation of neurotrophic factors enable psychedelics to promote neuronal survival and glutamate-driven neuroplasticity. Muscimol modulation of GABAR reduces Aβ-induced neurotoxicity and psychedelic Sig-1R agonists provide protective roles in Aβ toxicity. Classic psychedelics also activate mTOR intracellular effector pathways in brain regions that show atrophy in AD. The potential of psychedelics to treat AD involves their ability to induce structural and functional neural plasticity in brain circuits and slow or reverse brain atrophy. Psychedelics stimulate neurotrophic pathways, increase neurogenesis and produce long-lasting neural changes through rewiring pathological neurocircuitry. Psychedelic effects on 5-HT receptor target genes and induction of synaptic, structural, and functional changes in neurons and networks enable them to promote and enhance brain functional connectivity and address diverse mechanisms underlying degenerative neurological disorders. These findings provide a rationale for immediate investigation of psychedelics as treatments for AD patients.
Topics: Humans; Alzheimer Disease; Hallucinogens; Neurodegenerative Diseases; Brain; Atrophy
PubMed: 37451163
DOI: 10.1016/j.euroneuro.2023.07.003 -
Progress in Neuro-psychopharmacology &... Mar 2024Several observational studies have suggested that oral anticoagulants (OACs) might reduce the risk of dementia in the elderly, but the evidence is inconclusive. And the...
BACKGROUND
Several observational studies have suggested that oral anticoagulants (OACs) might reduce the risk of dementia in the elderly, but the evidence is inconclusive. And the consistency of this relationship across different OAC classes and dementia subtypes is still uncertain.
METHODS
To comprehensively evaluate this association, we applied Mendelian randomization (MR) combined with pharmacovigilance analysis. MR was used to assess the associations between genetic proxies for three target genes of OACs (VKORC1, F2, and F10) and dementia, including Alzheimer's disease (AD) and vascular dementia (VaD). This genetic analysis was supplemented with real-world pharmacovigilance data, employing disproportionality analysis for more reliable causal inference.
RESULTS
Increased expression of the VKORC1 gene was strongly associated with increased risk of dementia, especially for AD (OR = 1.28, 95% CI = 1.14-1.43; p value < 0.001). Based on pharmacovigilance data, vitamin K antagonists (VKAs, inhibitors targeting VKORC1) exhibited a protective effect against dementia risk (ROR = 0.43, 95% CI = 0.28-0.67). Additional sensitivity analyses, including different MR models and cohorts, supported these results. Conversely, no strong causal associations of genetically proxied F2 and F10 target genes with dementia and its subtypes were found.
CONCLUSIONS
This study reveals that the inhibition of genetically proxied VKORC1 expression or VKAs exposure is associated with a reduced risk of Alzheimer's dementia. However, there is little evidence to support similar associations with direct oral anticoagulants (F2 inhibitors and F10 inhibitors). Further research is warranted to clinically validate our findings.
Topics: Humans; Aged; Administration, Oral; Anticoagulants; Dementia; Genomics; Genome-Wide Association Study; Alzheimer Disease; Vitamin K Epoxide Reductases
PubMed: 38154516
DOI: 10.1016/j.pnpbp.2023.110929 -
The American Journal of Geriatric... Jul 2024
Topics: Humans; Dementia; Estrogens; Female; Risk Factors
PubMed: 38448304
DOI: 10.1016/j.jagp.2024.02.009 -
Pharmacology & Therapeutics Jan 2024Dementia is a common cause of disability and dependency among the elderly due to its progressive neurodegenerative nature. As there is currently no curative therapy, it... (Review)
Review
Dementia is a common cause of disability and dependency among the elderly due to its progressive neurodegenerative nature. As there is currently no curative therapy, it is of major importance to identify new ways to reduce its prevalence. Hypertension is recognised as a modifiable risk factor for dementia, particularly for the two most common subtypes; vascular dementia (VaD) and Alzheimer's disease (AD). From the current literature, identified through a comprehensive literature search of PubMed and Cochrane Library, this review aims to establish the stage in adulthood when hypertension becomes a risk for cognitive decline and dementia, and whether antihypertensive treatment is effective as a preventative therapy. Observational studies generally found hypertension in mid-life (age 45-64) to be correlated with an increased risk of cognitive decline and dementia incidence, including both VaD and AD. Hypertension manifesting in late life (age ≥ 65) was demonstrated to be less of a risk, to the extent that incidences of high blood pressure (BP) in the very elderly (age ≥ 75) may even be related to reduced incidence of dementias. Despite the evidence linking hypertension to dementia, there were conflicting findings as to whether the use of antihypertensives was beneficial for its prevention and this conflicting evidence and inconsistent results could be due to the methodological differences between the reviewed observational and randomised controlled trials. Furthermore, dihydropyridine calcium channel blockers and potassium-sparing diuretics were proposed to have neuroprotective properties in addition to BP lowering. Overall, if antihypertensives are confirmed to be beneficial by larger-scale homogenous trials with longer follow-up durations, treatment of hypertension, particularly in mid-life, could be an effective strategy to considerably lower the prevalence of dementia. Furthermore, greater clarification of the neuroprotective properties that some antihypertensives possess will allow for better clinical practice guidance on the choice of antihypertensive class for both BP lowering and dementia prevention.
Topics: Humans; Aged; Middle Aged; Antihypertensive Agents; Hypertension; Alzheimer Disease; Dementia, Vascular; Cognitive Dysfunction
PubMed: 38052309
DOI: 10.1016/j.pharmthera.2023.108575 -
European Journal of Medical Research Nov 2023From an initial pool of 2303 studies, ten eligible and potential studies were selected through rigor inclusion and exclusion criteria for this systematic review to... (Review)
Review
From an initial pool of 2303 studies, ten eligible and potential studies were selected through rigor inclusion and exclusion criteria for this systematic review to examine music therapy's effect on dementia. The review included 967 participants, with the majority being female. A significant number of studies were conducted in Taiwan. Although several cognitive ability assessment methods were employed in the selected studies, the Mini-Mental State Examination (MMSE) was the most commonly used tool for evaluating the effects of music therapy on dementia. Overall, the current review demonstrates that music therapy can be a valuable strategy for treating patients with dementia, with its outcomes including improved cognitive function and potentially slowing the progression of the disease's severity. Therefore, this study can significantly contribute to future studies and practices aimed at using music therapy to treat dementia.
Topics: Humans; Female; Aged; Male; Music; Dementia; Music Therapy; Asia; Cognition
PubMed: 37990277
DOI: 10.1186/s40001-023-01355-5 -
JAMA Internal Medicine Oct 2023Dementia is a life-altering diagnosis that may affect medication safety and goals for chronic disease management.
IMPORTANCE
Dementia is a life-altering diagnosis that may affect medication safety and goals for chronic disease management.
OBJECTIVE
To examine changes in medication use following an incident dementia diagnosis among community-dwelling older adults.
DESIGN, SETTING, AND PARTICIPANTS
In this cohort study of adults aged 67 years or older enrolled in traditional Medicare and Medicare Part D, patients with incident dementia diagnosed between January 2012 and December 2018 were matched to control patients based on demographics, geographic location, and baseline medication count. The index date was defined as the date of first dementia diagnosis or, for controls, the date of the closest office visit. Data were analyzed from August 2021 to June 2023.
EXPOSURE
Incident dementia diagnosis.
MAIN OUTCOMES AND MEASURES
The main outcomes were overall medication counts and use of cardiometabolic, central nervous system (CNS)-active, and anticholinergic medications. A comparative time-series analysis was conducted to examine quarterly changes in medication use in the year before through the year following the index date.
RESULTS
The study included 266 675 adults with incident dementia and 266 675 control adults; in both groups, 65.1% were aged 80 years or older (mean [SD] age, 82.2 [7.1] years) and 67.8% were female. At baseline, patients with incident dementia were more likely than controls to use CNS-active medications (54.32% vs 48.39%) and anticholinergic medications (17.79% vs 15.96%) and less likely to use most cardiometabolic medications (eg, diabetes medications, 31.19% vs 36.45%). Immediately following the index date, the cohort with dementia had a greater increase in mean number of medications used (0.41 vs -0.06; difference, 0.46 [95% CI, 0.27-0.66]) and in the proportion of patients using CNS-active medications (absolute change, 3.44% vs 0.79%; difference, 2.65% [95% CI, 0.85%-4.45%]) owing to an increased use of antipsychotics, antidepressants, and antiepileptics. The cohort with dementia also had a modestly greater decline in use of anticholinergic medications (quarterly change in use, -0.53% vs -0.21%; difference, -0.32% [95% CI, -0.55% to -0.08%]) and most cardiometabolic medications (eg, quarterly change in antihypertensive use: -0.84% vs -0.40%; difference, -0.44% [95% CI, -0.64% to -0.25%]). One year after diagnosis, 75.2% of the cohort with dementia were using 5 or more medications (2.8% increase).
CONCLUSIONS AND RELEVANCE
In this cohort study of Medicare Part D beneficiaries, following an incident dementia diagnosis, patients were more likely to initiate CNS-active medications and modestly more likely to discontinue cardiometabolic and anticholinergic medications compared with the control group. These findings suggest missed opportunities to reduce burdensome polypharmacy by deprescribing long-term medications with high safety risks or limited likelihood of benefit or that may be associated with impaired cognition.
Topics: Aged; Humans; Female; United States; Aged, 80 and over; Male; Dementia; Cohort Studies; Cholinergic Antagonists; Medicare Part D; Cardiovascular Diseases
PubMed: 37603340
DOI: 10.1001/jamainternmed.2023.3575 -
BMC Psychiatry Oct 2023Alzheimer's disease (AD) is a progressive neurological disorder and the most common cause of dementia. The clinical continuum of AD ranges from asymptomatic disease to...
BACKGROUND
Alzheimer's disease (AD) is a progressive neurological disorder and the most common cause of dementia. The clinical continuum of AD ranges from asymptomatic disease to mild cognitive impairment (MCI), followed by AD dementia, categorized as mild, moderate, or severe. Almost one-third of patients suspected of having MCI or mild AD dementia are referred to specialists including psychiatrists. We sought to better understand the role that psychiatrists play in the diagnosis, treatment, and management of patients with all-cause MCI or mild AD dementia.
METHODS
We conducted an anonymous, online survey among physicians in the United States between February 4, 2021, and March 1, 2021. We surveyed psychiatrists, primary care physicians (PCPs), geriatricians, and neurologists who treat patients with all-cause MCI or mild AD dementia.
RESULTS
A total of 301 physicians participated in the survey, 50 of whom were psychiatrists. Of their patients with all-cause MCI or mild AD dementia, psychiatrists reported personally diagnosing two-thirds (67%). Psychiatrists used various methods to diagnose MCI or mild AD dementia including mental status testing (94%), review of patient medical history (86%), and neurological exams (61%). Upon diagnosis, psychiatrists reported most commonly discussing treatments (86%), management strategies (80%), disease progression (72%), and etiology of MCI or mild AD dementia (72%) with their patients. Most psychiatrists surveyed (82%) reported receiving advanced formal training in MCI and AD dementia care, primarily via residency training (38%), continuing medical education (22%) or fellowship (18%). Additionally, almost all psychiatrists (92%) reported receiving referrals for ongoing management of patients with MCI or mild AD dementia, primarily from PCPs or neurologists. However, only 46% of psychiatrists viewed themselves as the coordinator of care for their patients with MCI or mild AD dementia.
CONCLUSIONS
Many psychiatrists indicated that they were well-informed about MCI and AD dementia and have a strong interest in providing care for these patients. They can provide timely and accurate diagnosis of clinical MCI and mild AD dementia and develop optimal treatment plans for patients. Although many psychiatrists consider other physicians to be the care coordinators for patients with MCI and mild AD dementia, psychiatrists can play a key role in diagnosing and managing patients with MCI and mild AD dementia.
Topics: Humans; Alzheimer Disease; Cross-Sectional Studies; Dementia; Cognitive Dysfunction; Psychiatry; Disease Progression
PubMed: 37794326
DOI: 10.1186/s12888-023-05129-5 -
Alzheimer's & Dementia : the Journal of... Jun 2024Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect... (Review)
Review
Two of every three persons living with dementia reside in low- and middle-income countries (LMICs). The projected increase in global dementia rates is expected to affect LMICs disproportionately. However, the majority of global dementia care costs occur in high-income countries (HICs), with dementia research predominantly focusing on HICs. This imbalance necessitates LMIC-focused research to ensure that characterization of dementia accurately reflects the involvement and specificities of diverse populations. Development of effective preventive, diagnostic, and therapeutic approaches for dementia in LMICs requires targeted, personalized, and harmonized efforts. Our article represents timely discussions at the 2022 Symposium on Dementia and Brain Aging in LMICs that identified the foremost opportunities to advance dementia research, differential diagnosis, use of neuropsychometric tools, awareness, and treatment options. We highlight key topics discussed at the meeting and provide future recommendations to foster a more equitable landscape for dementia prevention, diagnosis, care, policy, and management in LMICs. HIGHLIGHTS: Two-thirds of persons with dementia live in LMICs, yet research and costs are skewed toward HICs. LMICs expect dementia prevalence to more than double, accompanied by socioeconomic disparities. The 2022 Symposium on Dementia in LMICs addressed advances in research, diagnosis, prevention, and policy. The Nairobi Declaration urges global action to enhance dementia outcomes in LMICs.
Topics: Humans; Dementia; Developing Countries; Aging; Brain; Congresses as Topic; Biomedical Research
PubMed: 38696263
DOI: 10.1002/alz.13836