Journal of Alzheimer's disease reports最新文献

Background: Despite the availability of these therapies, maintaining long-term adherence remains a significant challenge.

Objective: This retrospective cohort study aimed to investigate 12-month and 5-year persistence with antidementia drug therapy in Germany and to examine the association between demographic and clinical variables and the risk of therapy discontinuation.

Methods: Patients aged 60 years or older from the IQVIA Longitudinal Prescription Database who received an initial prescription for antidementia therapy between 2016 and 2023 (index date) were included. Time to discontinuation was estimated using the Kaplan-Meier method, and a multivariable Cox proportional hazards model was used to assess associations between predefined variables and the risk of discontinuation.

Results: The study included 567,815 patients (mean age: 80.2 years, 59.1% female). Five years after the index date, 19.8% of dementia patients were still receiving therapy, with a 12-month persistence rate of 53.1%. Cox regression models conducted for the total population revealed that younger age (<70 versus ≥90 years; HR: 1.21; 95% CI: 1.19-1.23; 71-80 years versus ≥90 years; HR: 1.13; 95% CI: 1.11-1.14) was significantly associated with an increased risk of therapy discontinuation. Initiating therapy with memantine was associated with a slightly lower risk of discontinuation compared to donepezil (HR: 0.87; 95% CI: 0.86-0.87).

Conclusion: In this study, half of the patients discontinued antidementia therapy within one year and 80% within five years. Younger age was linked to a higher risk of therapy discontinuation, while memantine therapy was associated with improved persistence, potentially reflecting better adherence among patients with more advanced dementia.

Background: Adverse reproductive outcomes (AROs) in women can lead to the occurrence of a variety of diseases later in life. However, research on AROs and dementia risk in women has not been reported.

Objective: This study explored the effects of miscarriage and stillbirth on future dementia risk in women.

Methods: The Cox proportional hazards model was used to clarify the association between miscarriage, stillbirth, and dementia risk. In this cohort, only women with a history of miscarriage and stillbirth were selected. A genetic risk score for dementia was constructed, and the combined effect of miscarriage, stillbirth, and the genetic risk score for dementia on the future risk of incident dementia was determined.

Results: For each increase in the number of miscarriages and stillbirths, the risk of dementia increased by 5% and 22%, respectively. Compared to women who had a low genetic risk score, no miscarriages and at least one live-born infant, women with more than 3 miscarriages and a high genetic risk score had a significantly increased risk of dementia.

Conclusions: Our results indicate that miscarriage and stillbirth are associated with an increased risk of dementia, especially in women with a high genetic risk score.

Background: Dementia insurance, a private insurance product covering the first diagnosis of dementia of the insured, may be beneficial for asymptomatic individuals who recognize their own high genetic risk for Alzheimer's disease.

Objective: We aimed to examine the cost-benefit of dementia insurance in cognitively unimpaired individuals, stratified by APOE ε4 genotype.

Methods: A simulation study using 18 years of longitudinal data from National Alzheimer's Coordinating Center study to simulate the income and expenses of dementia insurance from the insured's perspective. Cognitively unimpaired participants at baseline (approximately n = 9000) were included, and the loss ratio (= total benefits gained / total premium paid) was calculated by APOE ε4 subgroup, applying the premium rates of actual insurance products in Japan.

Results: For individuals aged 60 or older with ≥ 10-year follow-up, the estimated loss ratio was highest in APOE ε4 homozygotes. However, even for this group, the 95% confidence interval for the loss ratio was either below or included 1.0, indicating no clear financial gain. Their loss ratio was approximately 3 to 4 times higher than for ε4-negative individuals, and 2 times higher than for ε4-heterozygotes.

Conclusions: Dementia insurance may be relatively more cost-beneficial for asymptomatic ε4-homozygotes in their 60 s or older compared to other genotypes over policy periods of 10 years or longer. However, it does not represent a clear financial gain for the insured, highlighting the need for careful consideration. Our study provides an important basis for further investigating the advantages and limitations of dementia insurance for individuals with high-risk gene.

Oropharyngeal dysphagia frequently occurs in persons living with Alzheimer's disease and related dementias (PLWD) and results in negative health consequences. Strength-based exercises may address swallowing biomechanical impairments. Expiratory muscle strength training (EMST) is an intervention examined in other neurodegenerative populations and has demonstrated promise for improving respiratory muscle strength and airway defense physiologic capacity, potentially improving swallowing safety. We describe a case of a patient with Alzheimer's disease who participated in five consecutive weeks of EMST. We demonstrate that EMST is a feasible intervention for PLWD. Further research should be conducted to assess efficacy and benefit of EMST for PLWD.

Cognitive dysfunction in the elderly is not only a disease but also could be considered a preclinical condition of Alzheimer's disease (AD), one of the most common types of dementia in the elderly. Therefore, treatment such as early detection and management of risk factors that could slow and prevent the onset of dementia is necessary for the elderly. Estrogen reduces the risk of AD in postmenopausal women. It has also been shown to reduce amyloid-β (Aβ) pathology in animal models of AD and suppress Aβ secretion from neuronal tissue. Estrogen receptors are involved in cognitive processes such as learning and memory, the formation of the hippocampus, the amygdala, and the cerebral cortex. Hormone replacement therapy (HRT) could improve cognition and thus delay the development of AD. Giving HRT after 9 years has been shown to increase the risk of breast cancer two-fold and cardiovascular disease. Phytoestrogens are hormones found in plants that can be an alternative to HRT. One of the foods that contains phytoestrogens and is widely consumed in Indonesia is tempeh. Isoflavone is a dominant phytoestrogen, structurally an estrogen-like substance, and functionally similar to 17β-estradiol. In this review article, we will discuss the role of tempeh isoflavones in a mechanism pathway on cognition.

Background: Early degeneration of the cholinergic nucleus basalis of Meynert contributes to cognitive decline in Alzheimer's disease (AD). Microstructural damage in downstream cholinergic tracts-the cingulum bundle (CGC), entorhinal cortex (EC), and uncinate fasciculus (UNC)-often precedes volumetric atrophy. While cholinesterase inhibitors (ChEIs) can preserve cortical and hippocampal volume, their influence on white-matter integrity is unclear.

Objective: To determine whether ChEIs slow microstructural decline in four cholinergic tracts (CGC, EC, UNC, posterior thalamic radiation [PTR]) in mild cognitive impairment (MCI), and whether baseline cognitive status modulates this effect.

Methods: Diffusion-tensor imaging from the Alzheimer's Disease Neuroimaging Initiative was analyzed in 46 MCI participants receiving donepezil or rivastigmine and 62 untreated MCI controls, each scanned serially over two years. Fractional anisotropy (FA) and mean diffusivity (MD) indexed tract integrity. Linear mixed-effects models tested time × medication × baseline cognition (ADAS-Cog13) interactions, adjusting for age, sex, APOE ε4, and white-matter hyperintensity burden.

Results: Across groups, CGC showed progressive degeneration (FA↓, MD↑; p < 0.001). Significant three-way interactions emerged for MD in bilateral CGC, FA in right EC, and MD in left PTR (all p < 0.01). ChEI users with milder baseline impairment (lower ADAS-Cog13) exhibited attenuated FA loss and MD increase, indicating slower microstructural decline; those with greater initial impairment derived minimal benefit. No medication effect was detected in UNC.

Conclusions: ChEIs confer tract-specific, stage-dependent protection of cholinergic white matter, particularly in early MCI. The findings underscore the value of initiating ChEI therapy before substantial cognitive deterioration and highlight the need for stage-tailored interventions aimed at preserving white-matter integrity in prodromal AD.

We analyzed how cardiovascular disease subtypes influence the prevalence and incidence of dementia among 30,582 individuals aged 50 and older in the National Alzheimer's Coordinating Center cohort. We calculated prevalence ratios (aPR) and hazard ratios (aHR), using models adjusted for age, sex, race, years of education, hypertension, diabetes, and dyslipidemia. Stroke (aPR: 1.26; 95% CI: 1.20-1.32) and history of arrhythmias (aPR: 1.17; 95% CI: 1.09-1.24) were associated with higher dementia prevalence. In survival analysis, stroke was associated with a 55% increased risk of incident dementia (aHR: 1.55; 95% CI: 1.36-1.77).

The FDA approval of disease-modifying Alzheimer's disease therapies marks a major shift in treatment but exposes a critical challenge: identifying patients during the mild cognitive impairment (MCI) stage when intervention is most effective. Despite early biological changes, most diagnoses occur after significant decline. Drawing from over 180 stakeholder interviews conducted through the NSF I-Corps program reveal major detection gaps across primary care, specialty access, and available tools. This commentary highlights the consequences of delayed diagnosis and proposes translational strategies to align early detection with therapeutic opportunity, positioning MCI as the critical window for Alzheimer's disease intervention.

We report a 76-year-old patient with mild cognitive impairment and APOE ε3/ε3 genotype who developed a rare pontine hemorrhage following treatment with lecanemab, an anti-amyloid-β monoclonal antibody for Alzheimer's disease. She was initially on clopidogrel and rivaroxaban; rivaroxaban was discontinued prior to lecanemab initiation. After two infusions, lecanemab was paused due to angina. She then underwent coronary stenting and was placed on dual antiplatelet therapy (aspirin and clopidogrel). Pontine hemorrhage occurred after twenty days. This case highlights heightened bleeding risk when lecanemab is combined with intensified antithrombotic therapy, even without APOE ε4 or significant cerebral small vessel disease load.

Background: Olfaction has enabled humans to survive and reproduce throughout their evolutionary history. Certain odors have been historically associated with danger while others, pleasure. Further, olfactory impairment is one of the earliest manifestations of neurodegeneration, such as Alzheimer's disease. Therefore, olfactory tests have the potential to reveal insights into a person's brain health. The landscape of orthonasal olfactory tools is vast, and many have been adapted for populations living in low- and middle-income countries, but challenges remain in the awareness of the utility of olfactory testing, effective deployment, and scalability.

Objective: This report explores the current landscape of olfactory tests, the potential for digital tests to provide scalable data in low-resource settings, and their potential applicability in the Alzheimer's disease and brain health space. We also describe the ScentAware digital odor identification test and present some preliminary findings from its use in Egypt, a site for the Davos Alzheimer's Collaborative's Global Cohorts Program.

Methods: The American University in Cairo in partnership with University College London collected olfactory data using the ScentAware test from 125 participants from the North African Dementia Registry, a longitudinal study of community dwelling adults over age 55 in Egypt and the surrounding Middle East and North Africa region.

Results: Participants' olfactory function measured by the culturally adapted ScentAware test somewhat correlated with language and memory, as assessed by the Egyptian Harmonized Cognitive Assessment Protocol battery.

Conclusions: Our adaptation of the ScentAware test suggests that digital olfactory assessment holds promise for cost-effective deployment at scale in a low-resource setting.