Breakthrough Clinical Results
The Alzheimer's Association International Conference® 2025 (AAIC®) presented new research on Alzheimer's disease and other dementias. Key findings include: lifestyle interventions improving cognition in at-risk older adults; new clinical practice guidelines for blood biomarker tests in diagnosis; a potential link between combined heart-health drugs and slower cognitive decline; a correlation between lead pollution and memory problems; benefits of lifestyle changes, particularly walking, for individuals with the APOE4 gene; slower cognitive decline in SNAP participants; real-world effectiveness of new amyloid-targeting drugs; and insights into sex-based differences in brain health. The conference attracted nearly 19,000 attendees and featured over 6,400 scientific submissions.
Key Highlights
- Lifestyle interventions improved cognition in older adults at risk of cognitive decline.
- New clinical practice guidelines released for using blood biomarker tests in Alzheimer's diagnosis.
- Combination of heart-health drugs may slow cognitive decline.
- Real-world studies confirm the effectiveness and patient satisfaction with new amyloid-targeting Alzheimer's drugs.
Incidence and Prevalence
Global Estimates of Alzheimer's Disease: Incidence and Prevalence
Alzheimer's disease (AD) is the most common cause of dementia and has affected more than 40 million people worldwide, with projections indicating this number will significantly increase in the coming decades.
Currently, an estimated 6.2 million Americans age 65 and older are living with Alzheimer's dementia, with projections suggesting this number could grow to 13.8 million by 2060 without medical breakthroughs to prevent, slow or cure the disease.
According to a 2025 study analyzing Global Burden of Disease (GBD) data from 1990 to 2021, the global average annual percentage change (AAPC) in dementia incidence was 0.06 (95% confidence interval [CI]: 0.05-0.09). For dementia prevalence, the global AAPC was 0.09 (95% CI: 0.08-0.10) during this period.
The burden of Alzheimer's disease and other dementias has risen globally over the past three decades, accompanied by increasing cross-country inequalities. The Global Burden of Disease has increased significantly from 1990 to 2021, and the burden of dementia increases with age and is projected to remain on an upward trend until 2040.
Significant disparities exist in the numbers, rates, and age-standardized rates of disability-adjusted life years across 204 countries/territories. The global AAPC in disability-adjusted life years for dementia was 0.03 (95% CI: 0.01-0.05) from 1990 to 2021, while the mean AAPC in age-standardized mortality rate for dementia remained stable at 0 (95% CI: -0.02 to 0.03).
Females demonstrated higher disability-adjusted life year numbers (rates) for all age groups affected by Alzheimer's disease and other dementias. Age-standardized disability-adjusted life year rates increased worldwide and were high in high-middle and middle sociodemographic index regions but increased faster in low (AAPC=0.227%) and low-middle (AAPC=0.244%) sociodemographic index regions.
The age-standardized incidence rate and age-standardized prevalence rate of dementia showed a positive association with sociodemographic index. Cross-country inequality analyses indicated that disability-adjusted life years of Alzheimer's disease and other dementias were skewed and higher in countries with higher sociodemographic development, and this inequality increased over time.
Biologically defined Alzheimer's disease is more prevalent than clinically defined probable Alzheimer's disease at any age and is 3 times more prevalent at age 85 years among both women and men, mostly driven by asymptomatic individuals with biological Alzheimer's disease.
In the United States, Alzheimer's is the sixth-leading cause of death and the fifth-leading cause of death among Americans age 65 and older. Between 2000 and 2019, reported deaths from AD increased more than 145%.
Over the next 40 years, Latinos are projected to have the largest increase in ADRD cases in the U.S. The prevention and control of dementia represents a long-term and formidable challenge globally.
Risk Factors and Comorbidities
Top 3 Risk Factors and Comorbidities for Alzheimer's Disease
1. Genetic Factors
The APOE ε4 allele stands as the most significant genetic risk factor for Alzheimer's disease (AD). Studies show it was "significantly high" in AD cases compared to controls with an odds ratio of 2.66. The presence of any APOE ε4 alleles was associated with 2.42 times higher odds of dementia in European ancestry populations and 1.77 times higher odds in African ancestry populations. Beyond APOE ε4, cumulative genetic risk contributes independently to dementia risk. The familial form (FAD) has been linked to markers on chromosome 21 in some families, representing another important genetic component.
2. Cardiometabolic Factors
Hypertension is identified as the most significant modifiable risk factor, comparable to the genetic risk factor APOE-ε4 allele. MCI patients who develop hypertension within 18 months after their first diagnosis have a significantly higher risk of AD onset (HR = 2.77). Cardiometabolic multimorbidity shows the highest risk of dementia onset (HR:3.27), followed by metabolic (HR:1.83) and cardiovascular (HR:1.81) multimorbidity. Other significant cardiometabolic factors include dyslipidemia, impaired glucose metabolism, and insulin resistance. There is a bidirectional relationship between Type 2 diabetes (T2D) and AD, where AD neuropathology accelerates the development of peripheral insulin resistance and progression of T2D.
3. Inflammatory and Metabolic Factors
The inflammatory burden index (IBI) was significantly higher in AD patients compared to control groups and was found to be a predictor for severity of cognitive impairment. C-reactive protein (CRP) levels and neutrophil count were significantly higher in AD patients. The hemoglobin, albumin, lymphocyte, and platelet (HALP) score was lower in AD patients and was a predictor for cognitive impairment severity. Oxidative stress and the accumulation of free radicals are involved in the pathophysiology of Alzheimer's disease. Metal homeostasis also plays a role, with significant differences in levels of total copper, free copper, zinc, copper/zinc ratio, and iron observed between AD cases and controls.
Additional factors that modify AD risk include advanced age, with prevalence increasing rapidly with age, education status, and sex differences. Metabolic dysfunction-associated steatotic liver disease (MASLD) and metabolic alcohol-associated liver disease (MetALD) are associated with increased risks of AD and vascular dementia. Stroke is associated with a fourfold increased risk of AD and may interact with APOE-ε4 to further increase AD risk.
Recent Studies
Recent Alzheimer's Disease Studies: Interventions and Outcomes
Lecanemab (ClarityAD/Study 301)
Lecanemab is a disease-modifying therapy targeting amyloid-beta. The phase III trial (identified by government identifier NCT03887455) demonstrated enhanced accuracy and precision across various endpoints. The study showed that incorporating AD prognostic covariates (APCs) reduced variance estimates by up to 19.1%, increased power to 90.2%, and reduced sample size by 27.2%. This amyloid-targeting therapy was evaluated using clinical outcomes including ADCOMS, CDR-SB, ADAS-Cog 14, and amyloid burden on PET. Meta-analysis confirmed that Lecanemab outperformed control groups on these measures.
Donanemab Phase 3 Trial
The donanemab phase 3 trial (2023) evaluated this amyloid-targeting therapy with a primary outcome measuring change in integrated Alzheimer Disease Rating Scale (iADRS) score from baseline to 76 weeks. The trial showed significant results with least-squares mean (LSM) change in iADRS score of -6.02 in the donanemab group versus -9.27 in the placebo group (difference, 3.25) in the low/medium tau population. Secondary outcomes included the Clinical Dementia Rating Scale Sum of Boxes (CDR-SB), with LSM change at 76 weeks of 1.20 with donanemab and 1.88 with placebo (difference, -0.67) in the low/medium tau population. Tau PET imaging was used to classify participants by tau pathology level.
NavegApp Study
The NavegApp study (2025) evaluated a serious game (SG) designed to assess three key components of spatial cognition (SC) as potential cognitive markers for early detection of Alzheimer's disease. The study demonstrated strong content validity with expert panel confirmation that tasks were representative (Aiken V=0.96-1.00) and relevant (Aiken V=0.96-1.00) for measuring SC components. Usability testing showed positive ratings for digital ergonomics from both experts and non-experts, with observable differences in usability perceptions among participants with sporadic mild cognitive impairment compared to cognitively healthy individuals (r 0.26-0.29).
Neuroinflammation Research
Research on neuroinflammation as a therapeutic target (2025) investigated how increasing regulatory T cells can decrease activation of microglia, proinflammatory cytokines, and astrocytes. Evidence suggested that increasing regulatory T cells count does prevent Alzheimer's disease symptoms and pathology. The study explored the potential of immunotherapy in slowing the progression of cognitive decline, focusing on key components of neuroinflammation including microglia, astrocytes, cytokines and CD8+ effector T cells.
Other disease-modifying therapies that have entered late-stage trials include Gantenerumab, Aducanumab, ALZ-801, ALZT-OP1, Simufilam, NE3107, Semaglutide, and GV-971.