Rising mortality related to early-onset Alzheimer’s disease in the United States: trends and disparities, 2003–2023. This retrospective population-based study used Centers for Disease Control (CDC) and Prevention WONDER data to examine early-onset Alzheimer’s disease-related mortality (EOAD-RM) in the United States (US) from 2003 to 2023. Among 5,167 EOAD-related deaths, 62.4% occurred in female patients, and the age-adjusted mortality rate (AAMR) increased from 0.08 to 2.06 per 1 million population. From 2015 to 2023, the annualized percentage change was 19.9% (95% confidence interval [CI]: 17.98–21.82), with increases observed across sex, race/ethnicity, and region. Women had a faster increase in AAMR than men, Black individuals had the greatest relative increase from 2018 to 2023 (206%), and the West and Midwest had the largest regional increases. Overall, EOAD-RM rose substantially over 2 decades, supporting further investigation into factors driving these mortality trends and disparities.
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Lifestyle interventions vs monoclonal antibodies in mild cognitive impairment and early Alzheimer’s disease: a comparative review of randomized controlled trials. This comparative review evaluated randomized controlled trials of multimodal lifestyle interventions (MMLIs) and monoclonal antibody (MAB) therapies in patients with mild cognitive impairment (MCI) or early Alzheimer’s disease (AD) using Alzheimer’s Disease Assessment Scale–Cognitive Subscale (ADAS-Cog) outcomes. Five MMLI trials reported ADAS-Cog improvements of 1.3 to 2.6 points, with benefits also reported for executive function, mood, gait speed, quality of life, and biomarkers. Three phase 3 MAB trials showed 1.4 to 1.5 points of ADAS-Cog preservation vs placebo, with robust amyloid clearance but modest clinical benefit. Relative benefit analysis showed 27% to 32% preservation with MABs compared to greater than 200% benefit with MMLIs. Overall, the review suggests that lifestyle interventions might provide broader cognitive and health benefits than MABs alone and supports future studies looking at lifestyle and pharmacologic approaches.
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Investigating the association between episodic and persistent depression in early to middle life with Alzheimer’s disease and related dementias in later life: a retrospective cohort analysis. This retrospective cohort study used TriNetX electronic medical records from 108 healthcare organizations to assess whether depression diagnoses from ages 18 to 44 years were associated with later Alzheimer’s disease and related dementias (ADRDs). A single episode of major depressive disorder (MDD) was most strongly associated with vascular dementia (odds ratio [OR]: 15.069; 95% CI: 13.159–17.255), while recurrent MDD was associated with increased risk across all dementia outcomes and showed the strongest association with AD (OR: 417.82; 95% CI: 373.785–460.879). Dysthymia showed intermediate associations between single-episode and recurrent MDD, with the greatest risk observed for vascular dementia (OR: 16.178; 95% CI: 12.277–21.317). Overall, chronic episodic depression showed the strongest association with later ADRD diagnoses, while dysthymia also appeared to contribute to ADRD risk.
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Diverging trends in Alzheimer’s disease mortality linked to psychoactive substance in White adult population in US, 1999–2023. This mortality analysis used CDC and Prevention WONDER data to examine deaths involving AD and psychoactive substance use (PASU) among White US adults aged ≥25 years from 1999 to 2023. Across 62,894 deaths, the age-adjusted mortality rate increased from 0.15 in 1999 to 1.98 in 2023, with the steepest rise from 1999 to 2005 and a nonsignificant decline from 2020 to 2023. Mortality was higher in men compared to women (1.70 vs 1.13), higher in nonmetropolitan compared to metropolitan areas (1.67 vs 1.14), and highest in the Midwest US (1.67). Overall, deaths involving AD and PASU increased substantially over time, with persistent demographic and geographic disparities.
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Associations between continuing medical education participation and real-world readiness for amyloid-targeting therapies in Alzheimer’s disease. This matched real-world analysis evaluated whether participation in a multi-activity continuing medical education (CME) curriculum improved clinician readiness to integrate amyloid-targeting therapies (ATTs) for AD. Clinician learners were matched 1:1 with nonparticipating controls (n=311 matched pairs) using baseline characteristics, and ATT initiation was tracked from May 2024 through January 2025. CME participants initiated 1,079 ATT treatments vs 548 in controls, corresponding to 531 incremental treatments with a 96.2% confidence level in statistical significance. Clinicians who completed multiple activities had greater increases than those completing a single activity, supporting the value of longitudinal, curriculum-based education. Overall, CME participation was associated with higher ATT initiation and greater real-world readiness to incorporate emerging AD therapies.
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Demographic variances and regional trends in Alzheimer’s and cardiac arrest-related mortality among older adults in the United States: a 20-year nationwide analysis. This nationwide mortality analysis used CDC and Prevention WONDER data to examine AD and cardiac arrest (CA)–related deaths among US adults aged 65 years and older from 1999 to 2020. A total of 254,007 deaths were identified, with mortality declining significantly from 2005 to 2013 (annual percent change [APC]: −2.93%; P<0.001) before mildly increasing, resulting in a slight overall rise from 1999 to 2020 (average APC: 0.32). AAMRs were higher in women compared to men (29.4 vs 23.5), highest among Hispanic individuals (39), and highest geographically in the West US (56.1), with California showing the highest state-level rate (93.6). Overall, AD and CA-related mortality showed modest long-term growth with notable sex, racial, geographic, and urban-rural disparities.
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Data-driven subtypes of subjective cognitive decline: neuropsychological profiles, Alzheimer’s disease biomarkers, and clinical trajectories. This study used Alzheimer’s Disease Neuroimaging Initiative data to identify data-driven subtypes of subjective cognitive decline (SCD) among 353 individuals with SCD, alongside 542 cognitively normal controls and 1,113 patients with MCI). Three SCD clusters were identified: a dysexecutive subtype with poorer executive functioning, fludeoxyglucose positron emission tomography hypometabolism, and phosphorylated tau and amyloid-beta 42 biomarker levels resembling MCI; a “worried-well” subtype with subjective memory and attentional complaints but no objective impairment; and an amnesic subtype with primarily memory deficits. Longitudinal analyses showed the greatest clinical decline in the dysexecutive cluster, suggesting higher risk for progression to neurodegenerative disease. Overall, the findings highlight the heterogeneity of SCD and suggest that some subtypes might reflect early neurodegeneration, while others might remain stable and potentially relate to psychological or affective factors.
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Feasibility, safety, and real-world implementation of a telehealth-delivered tDCS program for cognitive preservation in mild cognitive impairment and early Alzheimer’s disease. This real-world implementation study evaluated a remotely supervised, home-based transcranial direct current stimulation (tDCS) program paired with individualized cognitive-linguistic exercises in people with MCI or early AD receiving anti-amyloid therapy. Five participants completed daily Monday to Friday 30-minute tDCS sessions over 2 months, with stimulation individualized to clinical presentation and paired with computer-based training, tailored cognitive-linguistic rehabilitation, or both. All participants completed the program without adverse events, adherence exceeded 90%, and tolerability and satisfaction were high. Participants who continued extended treatment for up to 5 months maintained stable cognitive-linguistic performance despite progressive disease. Overall, telehealth-delivered tDCS appeared feasible, safe, and well tolerated, supporting future controlled trials of this care model in MCI and early AD.
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When sleep fails the brain: exploring early Alzheimer’s changes in young and midlife adults. This study examined links between sleep quality, memory, and early AD changes using an imaging cohort and US public health surveillance data. In the imaging cohort of 72 adults aged 20 to 55 years, “poor sleepers” had approximately 21% lower memory recall scores and significantly greater β-amyloid accumulation in the hippocampus and prefrontal cortex compared to “good sleepers” (P<0.05). Surveillance data showed that insufficient sleep is commonly reported among US adults, ranging from 30% to 46% by state, while AD mortality rates varied by state and demographic group. Age-adjusted AD mortality ranged from approximately 33 to 71 per 100,000 persons by race and ethnicity, and an estimated ≥6–7 million or more US adults aged ≥65 years have AD. Overall, the findings suggest that poor sleep in young and midlife adults could be associated with early memory decline and β-amyloid burden, supporting attention to sleep health as part of long-term brain health strategies.
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