Forensic science is a multidisciplinary field that plays a vital role in society by supporting criminal investigations and providing scientific evidence for judicial proceedings. Within this context, organic chemistry contributes fundamentally by enabling the structural elucidation of seized drugs and their intermediates, the synthesis of analytical reference standards for doping control, allied with a deeper understanding of drug metabolization, and the development of probes for detecting fingerprints and biological fluids. This review examines recent advances at the interface between organic synthesis and forensic science. The discussion is organized into three main application areas: drug identification, toxicology, and fingerprint analysis, highlighting how synthetic methodologies have been employed to address key challenges in each topic. Furthermore, this work aims to shed light on the broad range of opportunities for the organic synthesis community to contribute to the advancement of forensic science.
Animal cruelty is a persistent concern for animal welfare and society worldwide. In Thailand, the Prevention of Cruelty to Animals and Animal Welfare Act B.E. 2557 (2014) provides a legal framework to address animal abuse; however, effective enforcement remains constrained by limitations in investigative procedures and the limited integration of veterinary forensic science. Veterinarians from the Department of Livestock Development (DLD) play a central role in responding to cruelty reports, conducting inspections, and supporting legal processes. This study aimed to explore the attitudes of DLD veterinarians toward companion animal welfare, the effectiveness of existing animal welfare legislation, and the current and potential role of forensic science in animal cruelty investigations in Thailand. A cross-sectional qualitative study was conducted between August 2024 and December 2024. Eighteen veterinarians with DLD from six geographic regions of Thailand were recruited using stratified purposive sampling. Data were collected via a validated, open-ended online questionnaire that addressed animal welfare challenges, legal enforcement, investigative procedures, and forensic applications. Qualitative content analysis was performed using the NVivo software, with double-blind coding to enhance analytical rigor. The codes were organized into categories and overarching themes following inductive thematic analysis. Multiple interrelated drivers of companion animal cruelty were identified by veterinarians. The major welfare-related themes included a lack of owner responsibility and preparedness, insufficient knowledge and ethical awareness regarding animal care, socioeconomic constraints, deficiencies in stray animal management systems, weaknesses in law enforcement, and cultural attitudes that undermine animal welfare. While most respondents perceived the existing animal cruelty law as partially effective in reducing abuse, they highlighted critical gaps, including ambiguous legal definitions, inconsistent enforcement, and limited public awareness. The absence of standardized veterinary forensic protocols, limited forensic training, and restricted inspection authority were the primary factors driving investigative challenges. Respondents strongly supported the integration of forensic science, emphasizing its potential to improve evidentiary reliability, strengthen legal credibility, and enhance investigative outcomes, while also identifying the need for structured training programs and interagency collaboration. Companion animal cruelty in Thailand is driven by multifactorial welfare, legal, and societal challenges. Although current legislation provides a foundation for protection, the absence of standardized forensic practices limits investigative effectiveness. Strengthening veterinary forensic capacity through harmonized protocols, targeted training, and coordinated enforcement could substantially enhance animal welfare protection and support consistent application of animal cruelty legislation within a One Welfare framework.
Women constitute a minority among patients in forensic psychiatric care, which aims to improve the patients' health while ensuring safety for patients, caregivers, and society. Participation in forensic psychiatric care can be complex; its definition depends on the context and perspective and is influenced by several factors. This study examined the perceptions of female patients and caregivers regarding their participation, interactions, and experiences within the forensic psychiatric care environment. The participants (N = 108) completed validated questionnaires, including the Quality in Psychiatric Care Forensic Inpatient version, Verbal and Social Interactions, and EssenCES. The data were analyzed using both descriptive and analytical statistics. For female patients, establishing a care relationship and feeling a sense of cohesion with other patients, along with a therapeutic approach from caregivers, are crucial for perceived participation. The dual paradigm of medicine and law in forensic psychiatric care impacts both patients and caregivers. Safe wards and supportive care are essential for enhancing patients' well-being and helping them achieve their goals. Due to the results and the limited sample size, which reflects the actual low number of female patients, further research is needed. Also, to compare the differences (or similarities) between female and male patients.
The accurate documentation of bodies, injuries, death scenes, accidents, and crime scenes is fundamental to forensic investigations. Traditional two-dimensional (2D) photography and written reports have inherent limitations in representing complex spatial relationships. Recently, three-dimensional (3D) surface documentation technologies, including laser-scanning, structured light scanning, and photogrammetry, have been integrated into forensic practice to provide accurate, measurable, and reproducible digital evidence. This review provides an overview of current 3D methods and discusses their principles, advantages, and typical applications in documenting crime scenes and human remains. Furthermore, it introduces emerging image-based reconstruction approaches, such as neural radiance fields (NeRF) and 3D Gaussian splatting (3DGS), which generate high-quality reconstructions from multiple images. The integration of 3D data into immersive environments, such as virtual reality (VR) and augmented reality (AR), is also addressed, highlighting its potential in forensic analysis, courtroom presentation, and education. With the rapid evolution of 3D technologies, it is essential to understand the strengths and limitations of each technique in forensic applications. Future developments in algorithms and immersive integration will expand digital forensic capabilities.
Determining whether ligature marks represent antemortem or postmortem injuries is a critical issue in forensic practice because this distinction directly influences the reconstruction of perimortem events. Consequently, assessing the vital reaction of neck skin plays an essential role in evaluating the viability of compression-related injuries. Cathelicidin antimicrobial peptide (CAMP), a multifunctional host-defense peptide involved in inflammation, immune cell recruitment, and wound repair, may serve as a reliable molecular marker for wound vitality. In this study, we examined CAMP expression in 40 ligature mark samples (32 samples of hanging and 8 samples of ligature/manual strangulation) obtained during forensic autopsies, along with matched intact skin controls, all with postmortem intervals of ≤ 3 days. Immunohistochemistry revealed strong CAMP expression in epidermal keratinocytes and moderate expression in dermal cells at compression sites, whereas control skin showed only faint or absent staining. Morphometric analysis demonstrated that the ratio of CAMP‑positive keratinocytes and the number of CAMP-positive dermal cells were significantly higher in compressed skin than in controls, independent of age, sex or postmortem interval. Moreover, neither ligature type nor mode of neck compression also had no influence on CAMP expression in the keratinocytes or dermal cells. These findings indicate that CAMP expression reflects a biological response to antemortem neck compression and may provide an objective molecular marker for assessing wound vitality in forensic pathology. Furthermore, combining CAMP with other established biomarkers may enhance diagnostic reliability when evaluating antemortem neck compression injuries.
Falling trees and large branches can result in severe blunt trauma; however, detailed correlations between postmortem computed tomography (PMCT) and forensic autopsy findings in such deaths remain limited. We retrospectively analysed eight consecutive deaths occurring between 2012 and 2025 in which impact or compression by a tree trunk or large branch constituted the primary traumatic event and in which both PMCT and complete forensic autopsy were performed. Thin-slice PMCT of the head and trunk was obtained using standard brain, soft-tissue, lung, and bone windows, supplemented by a gas-optimised thoracic setting. Scene information, PMCT, and autopsy findings were integrated to determine the primary mechanism of death and to compare intracranial, thoracoabdominal, skeletal, and asphyxial injuries. Four lethal mechanisms were identified: instantly fatal head or brainstem injury (n = 2), haemorrhagic shock without cardiac rupture (n = 2), traumatic shock with cardiac rupture and/or aortic injury (n = 2), and asphyxia due to smothering or thoracic compression (n = 2). PMCT demonstrated complex fractures of the ribs, scapulae, spine, and pelvis, as well as haemothorax, haemoperitoneum, pneumomediastinum, and pre-existing coronary artery calcification, and suggested aortic injury in one case. However, brainstem lesions, precise sites of cardiac and aortic rupture, and low-contrast parenchymal injuries were identified only at autopsy. These results suggest that PMCT is valuable for delineating global injury patterns and high-energy marker lesions in falling-tree deaths, whereas full forensic autopsy remains essential for establishing the exact mechanism of death.
Down syndrome (DS), or trisomy 21 (T21), represents the most common genetic cause of intellectual disability worldwide and is associated with a wide range of medical, developmental, and neurodegenerative conditions, including a universal predisposition to early-onset Alzheimer's disease (AD). Since its establishment in 2014, the Trisomy 21 Research Society (T21RS) has provided a global forum for advancing DS research across disciplines and promoting translational efforts to improve health and quality of life. Every two years, T21RS hosts an international scientific meeting that brings together researchers, clinicians, self-advocates, families, and industry stakeholders. In 2024, the 5th T21RS International Conference was held in Rome, Italy, from June 5 to 8, under the theme "Promoting Research Excellence in Down Syndrome." The meeting brought together about 500 scientists from 26 countries across five continents, and more than 900 attendees overall, including families and caregivers. The scientific program featured 5 keynote lectures, 2 satellite meetings, 17 symposia, 7 nano symposia, 2 workshops, and 1 industry-focused session, totaling more than 150 oral presentations. More than 230 abstracts were presented as posters. The conference covered research across the lifespan of individuals with DS, spanning genomic and epigenetic regulation, molecular and cellular mechanisms, preclinical and experimental models, cognition and behavior, neurodevelopment, aging and neurodegeneration, co-occurring medical conditions, and therapeutic interventions. Dedicated sessions focused on capacity-building in DS research and societal engagement were established. Significantly, T21RS promoted inclusivity by supporting 60 young investigator fellowships, providing childcare awards, and organizing a two-day program for families and caregivers in collaboration with Italian DS associations. This proceeding summarizes the main scientific highlights of the 5th T21RS International Conference, reflecting the latest advances in DS biology, clinical research, biomarker development, and therapeutic innovation.
Despite the digital transformation of society, handwritten documents continue to be collected in various investigations, such as fraud investigations and drug trafficking. Recent research highlighted that handwriting offers not only comparative value (i.e. helping address a source question), but it also has the potential to infer a writer's background profile (i.e. helping address other questions than source). This study compared binary logistic regression (BLR) and classification & regression tree (CRT) models to infer a writer's cultural background based on handwriting features. An experimental two-step modelling approach was employed to distinguish Australian, Korean, and Vietnamese writers (N = 196) using categorical handwriting features coded from scanned handwritten texts. The first step was classifying Australian from non-Australian writers, and the second step was further specifically classifying non-Australians into Korean and Vietnamese. The results demonstrated how a two-step modelling framework could be operationalised for early-stage writer classification and highlighted its practical strengths and limitations. The BLR model provided statistical depths for detailed interpretation, and it achieved higher classification accuracy, 93.4% and 97.8% in each step. The CRT model also achieved a high accuracy rate, but lower than BLR with 86.7% and 94.2%. Furthermore, blind test results reflected the practical challenges and strengths of each model. The CRT model correctly classified six out of seven blind specimens while the BLR correctly classified three out of seven blind specimens. Each model presented distinct strengths as the BLR model provided rich detailed statistical outputs, such as odds ratios and significance levels, while the CRT model offered greater accessibility and usability for non-statistical experts. These findings suggest that model selection should balance interpretability, robustness and accuracy. Although more work is required until such models can be applied in practice, this study highlights the potential to extract operational insights from handwriting beyond traditional comparison methods, supporting intelligence-led workflows even when no comparison material is available.
Intellectual disability (ID) equivalence describes conditions in which individuals function cognitively and adaptively at levels comparable to ID without meeting IQ-based diagnostic criteria. Fetal alcohol spectrum disorder (FASD) is characterised by impaired executive and adaptive functioning despite IQs often above the ID threshold, suggesting functional overlap with ID. This meta-analytic study is the first to examine whether FASD and ID share vulnerabilities in interrogative suggestibility. Two PRISMA-guided systematic searches of six databases were undertaken, and identified studies involving FASD or ID. Bayesian random-effects meta-analyses were conducted on Gudjonsson Suggestibility Scale-2 outcomes: Yield 1, Yield 2, Shift, and Total Suggestibility. Individuals with FASD showed levels of interrogative suggestibility comparable to, and sometimes exceeding, those with ID across all indices. Effect sizes were large for both groups, with particularly elevated Shift scores in individuals with FASD. Both groups are highly vulnerable to leading questions and interrogative pressure. Individuals with FASD may be especially prone to changing responses following negative feedback, highlighting important forensic interviewing implications.
Elder abuse is an increasingly common problem in modern society, in the context of rapid population aging. Despite increasing awareness, this phenomenon remains heavily underreported, and effective interventions are yet to be made, thus leading to significant medical, social, and legal implications. The purpose of this review is to present an updated situation of the depths of elder abuse, presenting its prevalence both at the global and European level, the two main environments in which it is the most common (community and institutional settings), different forms of abuse, risk factors, and consequences for each one of them, as well as medico-legal aspects on the matter. A narrative review was conducted based on PubMed/MEDLINE, Scopus, and Web of Science databases, in association with data presented in reports from international organizations. The review included only articles published in English, in peer-reviewed journals, addressing elder abuse in adults aged 60 years and older, and those that didn't respect the criteria were excluded. Elder abuse comes in different forms, most of the time overlapping, with psychological abuse being the most prevalent. Each one of them has its own risk factors and specific consequences, but all of them will eventually lead to increased morbidity, accelerated cognitive impairment, and functional decline. In community settings, the elders usually experience abuse related to dependency on the family and social isolation, while in institutional settings, abuse is frequently associated with understaffing and inadequate care. From a forensic perspective, functional and cognitive decline complicate the proper documentation of the abuse. Thus, the role of the physician in providing legal support to the victim is essential. Elder abuse continues to be heavily overlooked, losing sight of the fact that its consequences extend beyond immediate physical harm, affecting the general physical and mental health of the victims. A possible solution to this problem is envisioned, with the purpose of raising awareness of this situation and contributing to a change in the perspective from which society looks at the elderly.
Giorgetti et al. report a carefully designed in vivo cross-over experiment showing that brief passive exposures to cannabis or "light cannabis" smoke inside a vehicle can deposit detectable Δ9-tetrahydrocannabinol (Δ9-THC) or cannabidiol (CBD) into hair, even after a validated dichloromethane washing step. Their findings are forensically relevant because washed-hair concentrations sometimes approached or exceeded Society of Hair Testing cut-offs used to infer active use. The work advances beyond in vitro models by using realistic exposure durations. However, two statistical practices warrant further examination: the repeated-measures structure from four volunteers contributing multiple samples was not fully accounted for in primary tests, and values below the limit of quantification were replaced by a constant equal to the limit of detection. These choices may underestimate variability and produce narrow confidence intervals. This discussion reanalyses the authors' tabulated data using linear mixed-effects models and maximum-likelihood Tobit regression. The qualitative conclusions remain consistent, but uncertainty estimates widen materially, suggesting the value of more conservative reporting in small-cohort forensic toxicology studies.
Lung cancer is the leading cause of global cancer-related morbidity and mortality, with tobacco smoking as its strongest risk factor. Nuclear factor erythroid 2-related factor 2 (NRF2) is a redox-regulated transcription factor frequently dysregulated in non-small cell lung cancer (NSCLC), leading to aggressive disease and resistance to therapy. In this study, we analyzed circulating cell-free tumor DNA from a real-world cohort to characterize clinicopathological features and identify risk factors associated with oncogenic NRF2 activation in inoperable NSCLC. Key findings were further validated using retrospective datasets. Our results demonstrate that NRF2 pathway-mutated NSCLC represents a smoking-associated, high-risk molecular subtype frequently accompanied by detrimental SMARCA4 mutations. Importantly, these co-occurring mutations cumulatively worsen clinical outcomes independently of other risk factors. We show that NRF2-mutated tumors generally exhibit lower leukocyte infiltration, while high tumor mutation burden independently correlates with increased cytotoxic T lymphocyte density, regardless of NRF2 status. Furthermore, our data indicate that NRF2 activation can be reliably identified through immunohistochemical detection of protein expression of markers AKR1B10 and AKR1C1, both of which correlate with inferior outcomes. As mutations in NRF2-regulating tumor suppressors KEAP1 and CUL3 are not confined to specific hotspot regions, our findings advocate for a multimodal profiling approach combining somatic mutation assessment with protein or transcriptomic evaluation of NRF2 targets. This comprehensive strategy effectively identifies oncogenic NRF2 hyperactivity, enhancing diagnostic accuracy and clinical decision-making in NSCLC management. © 2026 The Author(s). The Journal of Pathology published by John Wiley & Sons Ltd on behalf of The Pathological Society of Great Britain and Ireland.
Acute ischemic heart disease (AIHD) is a major cause of sudden cardiac death, yet postmortem diagnosis is difficult, particularly in early-phase ischemic injury or decomposed bodies. We investigated the diagnostic value of two molecular biomarkers—8-hydroxy-2′-deoxyguanosine (8-OHdG), indicating oxidative DNA damage, and N-terminal pro-brain natriuretic peptide (NT-proBNP), reflecting cardiac wall stress—in 67 human forensic autopsy cases (33 AIHD, 34 non-AIHD). Immunohistochemistry revealed significantly greater and more diffuse nuclear 8-OHdG expression in AIHD cardiomyocytes compared with controls. Postmortem blood NT-proBNP levels were also significantly higher in AIHD cases (2389.1 ± 499.6 pg/mL) than in non-AIHD cases (896.1 ± 190.1 pg/mL). No significant correlations were found between 8-OHdG expression and NT-proBNP levels, contraction band necrosis, postmortem interval, age, or sex, suggesting that these markers reflect distinct pathological processes—oxidative injury and hemodynamic stress. Both markers demonstrated postmortem stability, and their combined evaluation improved diagnostic confidence in cases with inconclusive histology. This dual-biomarker approach may enhance the accuracy of AIHD diagnosis in forensic practice and provide complementary insights into the molecular mechanisms underlying sudden cardiac death. The online version contains supplementary material available at 10.1038/s41598-026-38797-w.
Multiple sclerosis (MS) is a progressive, long‑term disorder affecting the central nervous system. The management and treatment of MS require significant medical resources, placing a heavy burden on both individuals and society. Autophagy is essential for the degradation of dysfunctional or excess cellular components. In the context of MS, autophagy exhibits dual roles, both protective and detrimental. On one hand, it mitigates disease progression by reducing oxidative stress and inflammation. On the other hand, autophagy activates various immune and supportive cells pivotal in MS pathogenesis. This review aims to explore the relationship between autophagy and MS, its impact on disease progression and the current challenges in this field.
Prolonged immersion in a reheated bathtub can cause extensive thermal alteration and produce intracranial findings that mimic traumatic lesions on postmortem computed tomography (PMCT). Here, we report a bath-related fatality in a woman in her late 60s in which PMCT demonstrated a crescent-shaped epidural collection along the right parietal convexity. The collection exhibited layered components, consisting of a fat-attenuation upper layer and a dependent low-attenuation layer with a small amount of gas. PMCT also demonstrated diffuse bilateral ground-glass opacities, bilateral pleural effusions, and left pneumothorax, as well as fluid accumulation in the paranasal sinuses and airway fluid with foam. At autopsy, extensive epidermal stripping and blistering with heat rigor were observed, and red frothy fluid was present within the airway. Autopsy revealed a brick-colored epidural deposit (approximately 15 g) without skull fracture, consistent with heat-coagulated blood. Toxicological analysis detected triazolam and mirtazapine in the blood. Drowning was considered highly likely; however, definitive confirmation was limited by severe systemic thermal alteration. This case highlights a forensic diagnostic pitfall in which heat hematoma-like epidural changes following prolonged hot-water immersion may mimic traumatic epidural hematoma on PMCT, underscoring the importance of integrating scene information, toxicology, PMCT, and autopsy findings.
The direct blood-alcohol biomarker phosphatidylethanol (PEth), especially its most abundant analogue 1-palmitoyl-2-oleoyl-sn-phosphatidylethanol (PEth 16:0/18:1) has gained increasing relevance in clinical and forensic applications for assessing alcohol consumption. Accurate quantification of PEth is essential to reliably differentiate between abstinence, moderate alcohol consumption and excessive alcohol intake. Measurement accuracy of PEth 16:0/18:1 by well-established liquid chromatography-tandem mass spectrometry (LC-MS/MS) approaches such as multiple reaction monitoring (MRM) can be confounded by the presence of the regioisomer 1-oleoyl-2-palmitoyl-sn-phosphatidylethanol (PEth 18:1/16:0) in samples and synthetic reference standards. To address this measurement uncertainty, we conducted a new assessment of the isomeric composition of six currently available reference materials from four suppliers using collision-induced dissociation/ozone-induced dissociation (CID/OzID). Examination of these synthetic compounds found a high degree of regioisomeric purity of > 95%. Thus verified, the relative abundance of two key LC-MS/MS transitions were compared across a range of collision energies for both reference materials and an exemplary set of 10 dried blood spot case samples. These findings suggest a significantly wider range of natural isomer distributions spanning both higher and lower regiochemical composition (88.8%-98.85%) than the reference materials but within a range that would not significantly impact clinical classification.
Sudden Unexplained Nocturnal Death Syndrome (SUNDS) is a lethal disorder with a largely elusive genetic etiology. While traditionally associated with cardiac channelopathies and cardiomyopathies, the role of skeletal muscle excitation-contraction (E-C) coupling genes, such as CACNA1S and RYR1, remains under-explored in its pathogenesis. This study aimed to investigate the potential contribution of CACNA1S and RYR1 variants to SUNDS susceptibility within a Thai cohort. We performed whole-exome sequencing (WES) on 98 Thai SUNDS cases following forensic autopsy. Variants were prioritized using dbNSFP annotations and public population databases. Furthermore, molecular modeling was employed to evaluate the structural impact of identified variants by comparing wild-type and mutant protein models. Genetic analysis identified 16 individuals (16.3%) carrying missense variants in CACNA1S and/or RYR1. In CACNA1S, we identified five rare variants (T55M, F275L, R865C, K962E, R1547Q) and three common variants (L458H, R1539C, L1800S). In RYR1, five rare variants (V347M, A612T, P1774L, E3397K, G3482S) and three common variants (P1773S, G2060C, E3578Q) were detected. These findings expand the known genetic architecture of SUNDS and suggest that variations in the E-C coupling machinery-specifically within CACNA1S and RYR1-may significantly contribute to the risk of sudden nocturnal death.
Alzheimer's disease (AD) is a chronic neurodegenerative disease that is frequent among the aged and is characterized by symptoms of memory loss. With the development of the disease, cognitive impairment becomes obvious and leads to a heterogeneous spectrum of mental and behavioral problems that put a heavy burden on families and the society. Recent investigations suggest that the phosphoinositide 3-kinase (PI3K)/protein kinase B (AKT)/mammalian target of rapamycin (mTOR) signaling pathway is important in AD. In this paper, we describe the detailed mechanisms of this pathway that are also involved in AD, and the current research status in terms of the relationship of the effects of acupuncture with it.
Necrotizing soft-tissue infection (NSTI) is a rapidly progressing, life-threatening disease that is difficult to diagnose based on clinical findings alone. NSTI often does not present with pus at the infection site, so it may not be suspected during an autopsy. Consequently, bacterial cultures are not performed, which hinders identification of the causative organism. In this study, we attempted to amplify the 16S ribosomal RNA (16S rRNA) gene (also referred to as 16S rDNA) from blood samples collected during forensic autopsies in two cases where death was suspected to be due to NSTI, as determined by postmortem histological examination. These samples had been stored frozen for up to 170 months. However, bacteriological testing was not performed at the time of autopsy because NSTI was not suspected. In one case, a 16S rRNA gene was amplified for Vibrio vulnificus, and in the other, for Streptococcus pyogenes (Group A Streptococcus). Based on the autopsy findings and laboratory results, it was determined that the NSTI caused by these bacteria was the most likely cause of death. These results suggest that amplifying bacterial 16S rRNA genes from frozen postmortem blood samples may help in future cases.
Life expectancy for individuals with Down syndrome (DS) has significantly increased, primarily due to medical advances. While DS is considered a genetically determined form of Alzheimer’s disease (DS-AD), with neuropathological markers evident by age 40, the onset of clinical dementia varies. Modifiable risk factors are thought to contribute meaningfully to dementia risk in the general population. Advances in intervention studies in the general population suggest cognitive decline can be reduced through multimodal lifestyle interventions, however no large-scale multimodal studies have been conducted in the DS population. A comprehensive search was conducted across five electronic databases—Medline, EMBASE, CINAHL, Web of Science, and ASSIA to identify studies that examined the relationship between lifestyle interventions and cognitive outcomes in adults with DS. The search combined database-specific controlled language with keywords related to exercise, diet, social activities, cardiovascular health, and brain stimulation. Studies included were peer-reviewed original research articles focusing on adults with DS and reported on cognitive outcomes or AD-related biomarkers. The search yielded 24,774 articles, with 16,868 remaining after duplicates were removed. A total of 44 articles met inclusion criteria across the domains of exercise, diet, cardiovascular health, social connectedness, and cognitive stimulation. Most studies focused on exercise, indicating some cognitive benefits, particularly in executive functions and working memory, though results were inconsistent, and many suggested the necessity of high adherence to intervention protocols. No studies were found that examined the direct impact of diet on cognition in DS. Findings on cognitive stimulation, cardiovascular health and social connectedness suggested potential but inconclusive benefits for cognitive function. This review underscores the significant gaps in research regarding non-pharmacological interventions for DS-AD. It highlights the need for tailored, well-structured studies to better understand and leverage potential cognitive benefits of lifestyle interventions in the DS population. Implementing such interventions early in life and before significant disease progression may help maintain quality of life and independence among individuals with DS. Future research should focus on comprehensive, multi-domain interventions to ascertain their efficacy and optimal application. The online version contains supplementary material available at 10.1186/s11689-026-09694-0.