Category: 8. Health

“Glucagon-like peptide 1 receptor agonists and combination medications (hereafter collectively referred to as GLP-1s) are shifting the treatment landscape for obesity. However, real-world challenges and limited clinician and public knowledge on nutritional and lifestyle interventions can limit GLP-1 efficacy, equitable results, and cost-effectiveness.”¹

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As the use of glucagon-like peptide-1 receptor agonists (GLP-1s) continues to grow for management of overweight and obesity, an increasingly bright light is revealing that pharmacotherapy alone is not sufficient to achieve long-term weight loss success. Although the medications, which include semaglutide (Ozempic, Wegovy) and tirzepatide (Mounjaro, Zepbound) have shown weight loss ranging from 5% to 18% in clinical trials, the real-world impact is often more modest, with high rates of discontinuation,² nutritional deficiencies, and weight regain.³ A new joint advisory from 4 leading professional organizations underscores the urgent need for comprehensive, patient-centered care that integrates nutrition, behavioral support, and lifestyle medicine to optimize the therapeutic potential of GLP-1s.¹

The advisory, titled “Nutritional Priorities to Support GLP-1 Therapy for Obesity,” was published in the American Journal of Clinical Nutrition and coauthored by representatives from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. It calls on clinicians to go beyond prescription-writing and actively engage patients in structured, evidence-based programs that support healthful eating, physical activity, and psychosocial well-being.¹

The Role of Comprehensive Support

GLP-1s are effective in promoting weight loss and offer additional benefits for conditions such as cardiovascular disease,⁴ heart failure,⁵ obstructive sleep apnea,⁶ chronic kidney disease,⁷ and in more recent studies, substance use disorders. However, therapy often comes with gastrointestinal side effects, including nausea, vomiting, and diarrhea, that can reduce appetite and compromise nutrient intake, the guideline authors stressed. As a result, patients may experience fatigue, hair loss, skin issues, poor wound healing, or muscle and bone loss, largely due to inadequate consumption of protein, vitamins, and minerals.¹

These physiological risks are compounded by behavioral and socioeconomic factors. Disordered eating patterns, low health literacy, food insecurity, and limited access to high-quality foods all interfere with adherence to nutritional guidelines. Furthermore, many clinicians have little time during routine visits to offer meaningful lifestyle counseling, and reimbursement mechanisms for health coaching and nutrition therapy remain limited.¹

“All these challenges may be partially mitigated by an evidence-based, structured lifestyle program, particularly around food, when prescribing GLP-1s for obesity,” advisory authors said. “However, practical guidance for clinicians to implement such an approach is limited.”

The financial barriers⁸ to overall success of GLP-1 therapy cannot be overlooked, the authors emphasize. Annual costs for GLP-1s can exceed $16,000, even with rebates or compounded formulations, and recent studies suggest they are not yet cost-effective relative to their impact on long-term health outcomes.¹

Patient-Centered Framework

To guide clinicians, the advisory proposes a structured approach built on the 5As framework: assess, advise, agree, assist, and arrange. This model supports ongoing dialogue, goal setting, and care coordination throughout the treatment journey. Eight key nutritional priorities are outlined to support patients using GLP-1s:

1. Initiation with a Patient-Centered Plan
   Treatment should begin with shared decision-making, realistic goal setting, and alignment with patients’ values and health priorities.
2. Baseline Nutritional Assessment and Screening
   A comprehensive evaluation of eating behaviors, psychosocial factors, body composition, and food security provides critical context for individualized care.
3. Management of Gastrointestinal Side Effects
   Strategies include modified dose titration, dietary modification, and education on symptom management to maintain adequate nutrient intake, especially protein.
4. Navigation of Dietary Preferences and Intake
   Shifts in taste or food tolerance reported with GLP-1 therapy require adaptive counseling to support the continued consumption of nutrient-dense, minimally processed foods.
5. Prevention and Mitigation of Nutrient Deficiencies
   Monitoring and supplementation of key nutrients—particularly iron, B vitamins, calcium, and vitamin D—are essential, especially when intake is reduced.
6. Preservation of Muscle and Bone Mass
   Incorporating resistance training and focusing on sufficient protein intake help mitigate the loss of lean body mass during weight reduction.
7. Maximizing Weight Loss Efficacy
   Behavioral support, physical activity, and personalized nutrition increase adherence and enhance pharmacologic effects.
8. Promotion of Other Lifestyle Measures
   Sleep quality, stress management, social support, and substance use cessation all contribute to better outcomes.

Team-Based Care, Emerging Tools

Given the time constraints in most primary care settings, successful implementation of this framework will depend in part on multidisciplinary collaboration, the advisory said. Referrals to community professionals, including registered dietitians and nutritionists, behavioral therapists, case managers, and social workers can help enhance behavior continuity and reinforce lifestyle strategies. Other strategies the advisory outlines include group medical visits, digital platforms, and telehealth services, which can all augment patient engagement and accountability.

Equity is a critical consideration. The advisory calls for systemic changes to improve access to medical nutrition therapy and behavioral health services, especially for marginalized communities. The expansion of “Food as Medicine” programs and culinary literacy initiatives may also bridge gaps in care.

Research Needs and The Future

The advisory authors are clear that additional research in the field of obesity medicine is essential. The field still lacks standardized language and diagnostic criteria for clinical and preclinical obesity, as well as data on the long-term impact of nutritional interventions in patients using GLP-1s, they wrote. Among other important investigations, future research should explore how dietary patterns influence endogenous GLP-1 activity, how best to maintain weight loss after medication discontinuation, and how to scale effective behavioral interventions across diverse populations.

GLP-1s represent a powerful tool in the treatment of obesity, but their potential is best realized when embedded in a robust, personalized plan that prioritizes nutrition, movement, and behavioral health, the group concluded. Clinicians prescribing these agents should ensure that every patient receives tailored guidance before, during, and after treatment that is supported by a multidisciplinary team. Integrating lifestyle medicine not only mitigates side effects and nutrient deficits, but also helps sustain functional health and weight loss long-term.

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References

1. Mozaffarian D, Agarwal M, Alexander L, et al. Nutritional priorities to support GLP-1 therapy for obesity: a joint Advisory from the American College of Lifestyle Medicine, the American Society for Nutrition, the Obesity Medicine Association, and The Obesity Society. Am J Clin Nutrition. 2025;122:344-367. doi:10.1016/j.ajcnut.2025.04.023

2. Halsey G. High Discontinuation Rates of GLP-1 RA-Based Drugs Linked to Weight Loss Far Below Phase 3 Clinical Trials. Patient Care. June 12, 2025. https://www.patientcareonline.com/view/high-discontinuation-rates-of-glp-1-ra-based-drugs-linked-to-weight-loss-far-below-phase-3-clinical-trials

3. Jennings S. Tirzepatide Demonstrates Sustained Weight Loss but Discontinuation Results in Weight Regain: SURMOUNT-4 Trial, Patient Care. December 13, 2025. https://www.patientcareonline.com/view/tirzepatide-demonstrates-sustained-weight-loss-but-discontinuation-results-in-weight-regain-surmount-4-trial

4. Halsey G. Oral semaglutide lowers risk of MACE 14% in high-risk adults: Final phase 3 SOULD trial readout. Patient Care. March 31, 2025. https://www.patientcareonline.com/view/oral-semaglutide-lowers-risk-of-mace-14-in-high-risk-adults-final-phase-3-soul-trial-readout

5. Halsey G. Semaglutide 2.4 mg significantly reduces HF symptom burden, body weight in adults with HFpEF and obesity. Patient Care. August 25, 2023. https://www.patientcareonline.com/view/semaglutide-2-4-mg-significantly-reduces-hf-symptom-burden-body-weight-in-adults-with-hfpef-and-obesity

6. Patient Care Editorial Staff. FDA approves tirzepatide as first drug for obstructive sleep apnea with obesity. Patient Care. December 20, 2024. https://www.patientcareonline.com/view/fda-approves-tirzepatide-as-first-drug-for-obstructive-sleep-apnea-with-obesity

7. Jennings S. Tirzepatide improves heart failure symptoms and renal function in people with obesity, CKD. Patient Care. April 11, 2025. https://www.patientcareonline.com/view/tirzepatide-improves-heart-failure-symptoms-and-renal-function-in-people-with-obesity-ckd

8. Halsey G. Cost of semaglutide, tirzepatide prohibitive despite significant benefits. Patient Care. March 14, 2025. https://www.patientcareonline.com/view/cost-of-semaglutide-tirzepatide-prohibitive-despite-significant-benefits

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A phase 3 study presented at the SDPA Annual Summer Dermatology Conference in Washington, DC, from June 25 to June 29th, demonstrated the effectiveness of once-daily roflumilast foam 0.3% over 8 weeks for psoriasis of the scalp and body.¹

“Patients reported improvements in symptoms, as well as a reduction in how psoriasis symptoms impacted daily life,” wrote investigators, led by Melinda J. Gooderham, MD, from SKiN Centre for Dermatology in Canada.

Common topical therapies for psoriasis, such as corticosteroids and calcineurin inhibitors, may lead to adverse events. For instance, corticosteroids may cause systemic adverse events, such glaucoma and loss of vision, growth retardation in infants and children, among others.2 Calcineurin inhibitors can result in a burning or stinging sensation, which should only last for about 15 – 20 minutes; this adverse event can occur after applying the topical and should settle down within the first week of use.3

Along with the adverse events, topical therapies for psoriasis also have limitations on duration of use and restrictions for use in thin-skinned areas, depending on the topicals’ strength. Moreover, patients may experience application difficulties that could reduce their adherence.

In ARRECTOR, a phase 3, randomized, parallel-group, double-blind, vehicle-controlled, multicenter trial evaluated once-daily roflumilast foam 0.3% for 8 weeks in children aged ≥ 12 years and adult patients with psoriasis of the scalp and body. Roflumilast, a PDE4 inhibitor formulated as a water-based foam or cream, does not contain skin-irritating ethanol, propylene glycol, or fragrances.

The primary endpoints included Scalp-Investigator Global Assessment (S-IGA) and Body-Investigator Global Assessment (B-IGA) success at week 8. S-IGA success was indicated by scores 0 (clear) and 1 (almost clear), along with a ≥ 2 grade improvement from baseline when rated from clear (0) to severe (4). B-IGA success was a score of 0/1 plus ≥ 2 grade improvement from baseline when rated from clear (0) to severe (4).

Secondary endpoints included the proportion of patients with 0 or 1 on SI/WI-NRS, which measured itch on a scale of 0 (no itch) to 10 (worst itch imaginable), and PSSI-75 and PSSI-100, referring to ≥ 75% and 100% reduction in PSSI, respectively. Other secondary endpoints included PSD, a validated 16-item questionnaire evaluating itch, pain, and scaling; scalpDex, a validated 23-item survey assessing the quality of life in patients with scalp dermatitis; and DLQI. Investigators also assessed safety and application-site tolerability.

Eligibility criteria included having at least moderate scalp and mild body psoriasis, BSA ≤ 25% (≤ 20% non-scalp BSA), PSSI ≥ 6, ≥ 10% scalp involvement, and PASI ≥ 2. Participants were randomized 2:1 to receive roflumilast foam 0.3% (n = 281) or vehicle foam (n = 151%) for 8 weeks.

The arms had similar demographic and baseline disease characteristics, with most patients (81.9%) previously using topical corticosteroids for psoriasis of the scalp and body. The roflumilast foam and vehicle foam arm had a mean age of 48.6 and 45 years, 54.1% and 60.3% females, respectively. Both arms at baseline had a mean S-IGA of 3.1 and a B-IGA of 2.8.

The analysis showed patients well-tolerated roflumilast foam 0.3%, which was consistent with safety outcomes reported in previous trials of roflumilast cream 0.3% in patients with psoriasis. Treatment-related adverse events (TEAEs) were mild or moderate in the roflumilast (96%) and vehicle (92%) arms, with 5.7% and 2% considered related to the study treatment, respectively.

The most common TEAEs were headache, diarrhea, COVID-19, and nausea. Discontinuations due to TEAEs were similar between the arms: roflumilast (n = 5; 1.8%) and vehicle (n = 2; 1.3%).

At week 8, significantly more patients on roflumilast achieved S-IGA success, B-IGA success, SI-NRS/WI-NRS 0/1, PSSI-75/100, and improvement in PROs, compared with the control arm (P < .0001). Furthermore, investigators observed improvements in patient-reported Scalpdex and PSD component scores with roflumilast as early as week 2 and continued through week 8.

“This is also in line with significant improvement (P<0.05) in scalp itch (SI-NRS) and worst itch (WI-NRS) previously observed within 24 hours after the first application of roflumilast foam 0.3%,” investigators concluded.

References

1. Gooderham M, Alonso-Llamazares J, Bhatia N, et al. Roflumilast Foam 0.3% in Patients with Psoriasis of the Scalp and Body: Improvements in Patient-Reported Outcomes in the ARRECTOR Trial. Presented at 2025 SDPA in Washington DC from June 25 – June 29th.

2. 2 Dhar S, Seth J, Parikh D. Systemic side-effects of topical corticosteroids. Indian J Dermatol. 2014 Sep;59(5):460-4. doi: 10.4103/0019-5154.139874. PMID: 25284850; PMCID: PMC4171913.

3. Topical Calcineurin Inhibitors (TCIs). Eczema Society. https://eczema.org/information-and-advice/treatments-for-eczema/topical-calcineurin-inhibitors/. Accessed July 8, 2025.

Liquid biopsies are tests that detect signs of cancer through a simple blood draw. Unlike traditional biopsies, which require removing a piece of tissue, a liquid biopsy typically looks for mutations or modification changes in fragments of DNA from cancer cells circulating in the blood. While liquid biopsies are a promising, non-invasive way to detect and monitor cancer as it progresses, they aren’t as sensitive or accurate for the early stages of disease.

Researchers at the University of Chicago have now developed a more sensitive liquid biopsy test that uses RNA instead of DNA for detecting cancer. Using blood samples from patients with colorectal cancer, the test was able to detect the earliest stages of the disease with 95% accuracy, vastly improving on current, commercially available, non-invasive testing methods.

Challenges to early diagnosis

When tumor cells die, they disintegrate and release particles of genetic material into the bloodstream. Standard liquid biopsies rely on this floating DNA, called circulating cell-free DNA (cfDNA) to detect cancer. In the early stages of disease when tumor cells are still growing and thriving, however, there isn’t very much cfDNA in the bloodstream.

“That has been a major challenge for early diagnosis. You just don’t have enough tumor DNA released into the blood,” said Chuan He, PhD, the John T. Wilson Distinguished Service Professor of Chemistry and Professor of Biochemistry and Molecular Biology at UChicago. “That was a challenge for us and everyone else to do early diagnosis of colon cancer, so we decided to look at RNA instead.” Dr. He is the senior author of the new study, published this week in Nature Biotechnology.

RNA is a transitional form of genetic code that copies and carries out instructions from DNA to produce proteins that cells need. Analyzing RNA is a good proxy for genetic activity, because the presence of RNA means that cells are busy doing things and building proteins.

For the new study, graduate student Cheng-Wei Ju and Li-Sheng Zhang, PhD, a former postdoc in Dr. He’s lab who is now a faculty member at the Hong Kong University of Science and Technology, began to investigate the possibility of using circulating cell-free RNA (cfRNA), instead of cfDNA, for the diagnosis and detection of cancer.

Measuring the simple abundance of RNA molecules in the blood isn’t always reliable, however, because amounts can vary greatly depending on the timing and preparation of samples. Dr. He’s lab specializes in studying the biological functions of RNA modifications, chemical changes made to RNA molecules that alter their activity.  So, for the new study, the researchers focused on analyzing RNA modification levels in blood samples, which remain relatively stable no matter how much RNA is present. For example, if an RNA transcript is modified by 30%, that percentage remains that the same whether it is measured on 100 or 1,000 copies.

Detecting changes in the microbiome

The team worked with samples from colorectal cancer patients provided by gastroenterologist and longtime collaborator Marc Bissonnette, MD, Associate Professor of Medicine at UChicago. To their surprise, not only were they able to measure modifications on cfRNA from human cells, but they were also able to detect RNA from gut microbes as well. Billions of bacteria coexist with us inside the digestive system, and in the presence of a cancerous tumor, their activity changes too.

Drawing on previous research in plants, Dr. He and his team knew that RNA modification levels reflect an organism’s state: the more active the organism, the more modifications are made to certain RNAs to sustain that activity. This same pattern was observed in the colorectal cancer samples as well.

“We found that RNA released from microbes has substantial differences between cancer patients versus healthy individuals,” Dr. He said. “In the gut when you have a tumor growing, the nearby microbiome must be reshaped in response to that inflammation. That affects the nearby microbes.”

The microbiome population also turns over much more quickly than human cells, with more cells dying more often and releasing RNA fragments into the bloodstream. This means that a test measuring modifications on microbial RNA can detect possible cancerous activity much earlier than tests that rely on DNA released by human tumor cells.

Commercial tests that measure DNA or RNA abundance in the stool are about 90% accurate for later stages of cancer, but their accuracy drops below 50% for early stages. The new RNA modification-based test was almost 95% accurate overall, and also accurate at the earliest stages of cancer.

“This is the first time RNA modifications have been used as a potential biomarker for cancer, and it looks to be much more reliable and sensitive compared to RNA abundance,” Dr. He said. “Being able to detect the cancer at those early stages is unprecedented.”

The study, “Modifications of microbiome-derived cell-free RNA in plasma discriminates colorectal cancer samples,” was supported by the Ludwig Center for Metastasis at the University of Chicago, the Rolfe Foundation, the National Institutes of Health, the Hong Kong Research Grants Council, and the Howard Hughes Medical Institute.

Additional authors include Ruitu Lyu, Han Li, Jiangbo Wei, Urszula Dougherty, Akushika Kwesi, Alexander Luna, Xuanhao Zhu, Xiaolong Cui, Bochen Jiang, Yiyi Ji, Peng Xia, Diana C. West-Szymanski, Chenxi Sun, Yuhao Zhong, Chang Ye, Angelica Moran, Christopher Lehmann, and Eric Pamer from UChicago; Alberto J. Parra Vitela from Advocate Lutheran General Hospital; Shenghai Shen from the Hong Kong University of Science and Technology; Yunzheng Liu from the California Institute of Technology, Liangliang Wang from the Chinese Academy of Sciences; Yuzhi Xu from New York University; and  Wei Zhang from Northwestern University.

A large prospective study published in Molecular Nutrition and Food Research reveals that a healthy plant-based diet is linked with a reduced risk of inflammatory bowel disease.

For the study, 143,434 individuals in the UK reported on their dietary intake. During an average follow-up of 14.5 years, 1,117 participants developed inflammatory bowel disease-795 cases of ulcerative colitis and 322 cases of Crohn’s disease.

A healthy plant-based diet was associated with an 8% lower risk of ulcerative colitis, and a 14% lower risk of Crohn’s disease. An unhealthy plant-based diet was associated with a 15% higher risk of Crohn’s disease, with results suggesting that this was in part due to higher intake of vegetable oils and animal fats. Fruits and vegetables were identified as protective factors against inflammatory bowel disease.

Blood analyses suggested that the benefits seen in this study might be explained by the anti-inflammatory properties of plant-based foods.

Our research indicates that a healthy plant-based diet may protect against inflammatory bowel disease, with its anti-inflammatory properties playing a key role.”

Zhe Shen, MD, corresponding author of the Zhejiang University School of Medicine, China

By mapping millions of real patient health records, UCLA scientists have uncovered four unique and predictable routes to Alzheimer’s, reshaping how we detect, understand, and potentially prevent the condition.

Study: Identifying common disease trajectories of Alzheimer’s disease with electronic health records. Image credit: Vitalii Vodolazskyi/Shutterstock.com

University of California, Los Angeles researchers identified four distinct pathways leading to Alzheimer’s disease. The study is published in eBioMedicine.

Background

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder characterized by memory loss, cognitive decline, and difficulty performing daily activities. The prevalence of AD and AD-related dementia is steadily increasing worldwide. In the United States, over 6.7 million people live with these conditions, which is projected to reach 13 million by 2050.

Several risk factors have been identified for AD, including cardiovascular disease, hearing loss, depression, diabetes, traumatic brain injury, and physical inactivity. Developing preventive, diagnostic, and therapeutic strategies for AD requires an in-depth understanding of how these risk factors co-occur and in what sequence they emerge, rather than analyzing individual risk factors. 

Evaluation of the timing and sequence of potential risk factors is particularly important for accurate AD risk prediction and identification of effective time frames for applying preventative measures or treatments. This study used millions of electronic health records to identify disease pathways that sequentially progress toward AD.

The Study

The researchers analyzed health data from 24,473 patients in the University of California Health Data Warehouse. They validated the findings in the nationally diverse All of Us Research Program, a diverse, nationally representative cohort.   

After filtering out diagnoses that were not positively associated with subsequent AD, researchers identified 5,762 patients who contributed 6,794 unique disease trajectories of AD. Disease trajectory is defined as a sequence of health events over time occurring irregularly and encompassing diagnoses, medications, procedures, and laboratory tests. Each trajectory included at least three temporally ordered diagnoses, and many patients were found to follow more than one distinct disease path, with up to three trajectories per individual.

Researchers mapped the temporal relationships between diagnoses leading to AD using advanced computational methods, including dynamic time warping, a method for comparing time series with irregular timing, k-means clustering, and network analysis.     

Key findings

The study identified four distinct disease trajectories leading to AD. These trajectories were: a mental health trajectory representing psychiatric conditions leading to cognitive decline; an encephalopathy trajectory representing brain dysfunctions that escalate over time; a mild cognitive impairment trajectory representing gradual progression of cognitive decline; and a vascular disease trajectory representing cardiovascular conditions contributing to dementia risk.

Each pathway had characteristic demographic features, comorbidity patterns, and progression rates, suggesting different progression trajectories for different populations.

The mental health trajectory focusing on depressive episode (F32) mainly affected women and Hispanic people and progressed to AD.  The mild cognitive impairment trajectory showed the progression from mild cognitive impairment (G31.84) to AD, and the vascular disease trajectory exhibited the longest electronic health record histories and the highest comorbidity burden, which highlights the chronic nature of cerebrovascular disease.

The encephalopathy trajectory was associated with the most rapid progression to AD and subsequent death, highlighting a more aggressive disease course. The study further found that the encephalopathy cluster showed the shortest interval from the first disease indicator to AD diagnosis, and from AD diagnosis to death, suggesting a faster disease course in that subgroup.

The presence of shared vascular risk factors such as hypertension across multiple trajectories indicates that these distinct disease progression pathways may be associated with common pathophysiological mechanisms. These findings highlight the importance of considering and managing shared risk factors to prevent the progression of multiple disease pathways to AD.

The study found consistent directional ordering for approximately 26% of diagnostic progressions regarding directionality of relationships within these trajectories. For example, essential hypertension is frequently followed by depressive episodes, which then progress to AD, suggesting a potential causal sequence.

The validation of study findings in the All of Us Research Program highlighted the generalizability of these trajectories across diverse populations and healthcare settings. These progression trajectories were found to predict the risk of AD more accurately than individual risk factors.

As researchers suggest, healthcare professionals can use these trajectories to identify high-risk patients early, develop targeted interventions, and restrict harmful consequences.

The study used causal inference modeling (Greedy Equivalence Search) to identify likely directional links between diagnoses within each trajectory. The encephalopathy cluster showed more consistent directional relationships (42.9%), indicating a more substantial potential for causal interpretation in this group.

The researchers also constructed simplified “backbone” networks to highlight the most common disease sequences within each trajectory, using modularity-based pruning to reduce noise and emphasize dominant patterns.

Study significance

The study provides a comprehensive framework for identifying distinct and interconnected disease progression routes that lead to AD. This approach can be applied in different clinical settings to improve risk assessment, timely diagnosis, and targeted interventions. Healthcare professionals should consider the cumulative impact of sequential disease progression while assessing AD risk.

The distinct trajectories identified in the study suggest that AD may develop through multiple pathways. The identification of specific risk factors such as depression, cerebrovascular disease, and other neurodegenerative conditions that often precede AD by several years provides opportunities for early intervention.

The dataset analyzed in the study excluded patients older than 90 years, which may restrict the generalizability of its findings to the population with a high prevalence of AD. Furthermore, health data was collected from six academic health systems in California, which may limit representativeness relative to population-based samples.

Potential misclassifications of AD patients in electronic health records may affect the study findings. Given this concern, researchers advise interpreting these trajectories as pathways leading to clinically diagnosed AD rather than biologically confirmed AD, which would require biomarkers for amyloid or tau pathology. Some diagnostic codes like “unspecified dementia” may reflect temporary or transitional clinical labels, highlighting the real-world complexity of disease classification in health records.

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