Background Noncommunicable diseases are the leading cause of death and disability worldwide, although many of their detrimental health effects can be prevented by lifestyle changes. Despite growing public and individual recognition of the importance of prevention, adherence to recommended measures is limited. We refer to this discrepancy between knowledge and action, specifically in relation to preventive lifestyle behavior, as lifestyle dissonance. Methods This paper presents a narrative synthesis and aims to provide a conceptual framework for communication with patients and the public that includes neurobiological and evolutionary perspectives. It discusses interactions between neural reward systems, executive control mechanisms, and contemporary environmental triggers, including nutrition, exercise, sleep, and stress, as examples of the six pillars of lifestyle medicine. Results We propose that lifestyle dissonance can serve as a didactic label in communication with patients and the public to explain the mismatch between evolved neural mechanisms and the modern environment. Rather than a sole failure of willpower, non-adherence to preventive lifestyle measures is partly founded in a conflict within neural circuitry. Patient education regarding the brain's underlying processes and their influence on behavior has the potential to enable individuals to actively redesign their actions, train their reward systems, and thus reinforce healthy behavior. Conclusion Integrating a narrative on neurobiological mechanisms into public health and clinical practice strategies should thus be aimed at helping bridge the gap between intention and sustainable preventive behavior. This conceptual framework provides a basis for supporting patients and the public in achieving lifestyle goals and improving the effectiveness of preventive measures.

Cognitive aging is shaped by genetic variation, environmental factors, and health-related conditions. Until now, it is largely unclear why some individuals maintain their cognitive function, and others show progressive cognitive decline. This study uncovered determinants of distinct cognitive aging trajectories in the older population. To approach the inter-individual variability in cognitive aging, we clustered n = 696 dementia-free individuals from the prospective TREND study based on their longitudinal changes in comprehensive cognitive testing every 2 years over 13 years on average. Identified subgroups of cognitive aging were tested for differences in general physical health, motor function, mental and neuropsychological health, personality, lifestyle, diet, and genetic and biofluid markers as observed at the phenotypes’ initial records. Comparing the best- and lowest-performing subgroups of cognitive aging, we found that individuals who maintain high cognitive function compared to those with low baseline and progressive cognitive decline showed significant faster gait speed, higher health-related quality of life, did sports and cognitive stimulating activities more frequently, and reported higher plant-based foods intake. Although there are fewer phenotypic differences involving the intermediate subgroups of cognitive aging, the best-performing subgroup compared to all other subgroups showed higher plant-based foods intake. Overall, this study identifies distinct, data-driven subgroups of long-term cognitive aging trajectories and reveals factors associated with these divergent paths using deeply phenotyped data. The findings highlight the substantial heterogeneity of cognitive aging and suggest that favorable trajectories are linked to modifiable behavioral and health-related characteristics, providing a foundation for future multidisciplinary strategies to promote healthy cognitive aging.

REM Sleep Behaviour Disorder (RBD) is a hallmark of the prodromal phase of α-synucleinopathies. We aimed to describe the prevalence of probable RBD and to assess its associations with demographics, cognition, and location in a large sample of older adults in Luxembourg, as a first step toward identifying individuals with RBD symptoms for future prodromal-marker assessment. In 2021, residents of Luxembourg aged 55–75 were invited to complete an online survey including the RBD Screening Questionnaire (RBDSQ); with a threshold of ≥ 7 defining screen-positive probable RBD (sppRBD). Screen-positive participants underwent a telephone interview, and those confirmed were categorised as telephone-assessed probable RBD (pRBD). Bayesian spatial mapping assessed the geographical distribution of pRBD, and logistic regression identified determinants of sppRBD and pRBD. Among 15,915 participants (54% male; median age 62 [IQR 58–67]), 12.4% had sppRBD. The telephone interview confirmed only 34.8% of these as pRBD, yielding a projected prevalence of 4.3%. Self-reported cognitive impairment, male sex, and Portuguese as questionnaire language were associated with pRBD, which showed heterogeneous geographical distribution. Online questionnaires may yield false positives, potentially reflecting e-health literacy issues; therefore, a confirmation step is essential. This analysis identifies individuals with RBD symptoms warranting further prodromal-marker assessment, a candidate group for, rather than a validated instance of, an at-risk-for-α-synucleinopathy cohort.

Gait abnormalities are key features of Parkinson’s disease (PD) and might be present in isolated REM Sleep Behavior Disorder (iRBD), a prodromal marker of alpha-synucleinopathy. To assess spatio-temporal gait parameters from prodromal (iRBD) to early/moderate PD stages in normal, fast and dual-task conditions. This prospective multicenter study included two independent cohorts with Polysomnography-confirmed iRBD, drug-naïve PD (naïve-PD), early and moderate treated PD (early-PD, mid-PD), and age-matched healthy controls (HC). Gait was assessed using mobile health technology. A total of 324 participants were enrolled: 194 in the Digital Neurological Assessment (DNA) cohort (23 iRBD, 57 naïve-PD, 49 mid-PD, 65 HC) and 130 in the TPA cohort (28 iRBD, 34 early-PD, 68 HC) composed from TREND, PASS-PD and ABCPD cohorts. In the two independent cohorts, iRBD and early PD (treated and non-treated) showed higher step time compared to HC, especially during dual-task gait. In fast walking, all patient groups had longer step time than HC. Step length was control-like in iRBD and early treated PD, whereas it was lower in both naïve and moderate stages PD in all different task conditions. Temporal gait parameters, especially during dual task walking, are sensitive markers of prodromal PD whereas reduced step length is occurring only in phases when PD diagnosis is already possible. These cross-sectional data need a further validation on ongoing longitudinal studies in prodromal and early stages PD.

Parkinson's disease (PD) affects physical activity, and physical activity reduces the burden of PD. Although shown in studies using inertial measurement units (IMU), it remains unclear at which position physical activity change can best be detected in this population. Within the FAIRPARK-II trial, a subgroup of 25 newly diagnosed persons with PD (pwPD) not taking disease-specific medication yet documented their physical activity and, in parallel, wore IMUs on the most affected ankle, wrist and the lower back for two weeks. Participant-reported physical activity was transformed into Metabolic Equivalents of Tasks (METs) in 15-minute intervals using The Compendium of Physical Activities; Euclidean Norm Minus One (ENMO) values were calculated and averaged over the same intervals for the IMU data. Data of at least 3 days with at least four simultaneous 15-minute epochs of both valid IMU and diary data within the time window (9.00 to 18.00) per participant was included, resulting in a total of 8,494 15-minute epochs used for this analysis. Root mean square error (RMSE) values were calculated between scaled normalized IMU-derived ENMO and normalized MET values for each of the nine IMU-MET combinations (three IMU positions × three MET intensity levels). The wrist and lower back IMU showed comparable RMSE values across all MET intensity levels, with both IMU positions showing lower RMSE values than the ankle position. Tremor affected RMSE negatively, whereby the lower back position may be slightly favorable for the assessment of physical activity in those with tremor. This prospective longitudinal dataset from a very rare cohort provides novel insights into the assessment of physical activity during the earliest clinically evident phase of Parkinson's disease without disease-specific medication, which may inform future clinical trials and observational studies.

Parkinson’s disease (PD) is the fastest growing neurological disorder worldwide and, together with other movement disorders, belongs to a group of chronic neurological conditions associated with a substantial burden for affected individuals, caregivers, and healthcare systems. Despite significant advances in symptomatic treatment, disease-modifying therapies remain unavailable, shifting increasing attention toward prevention as a key therapeutic strategy. In this narrative we primarily focus on PD, as the epidemiologically most challenging condition and the one for which the most comprehensive evidence base for preventive strategies has been established. Preventive approaches relevant to other movement disorders are briefly discussed to highlight other promising targets requiring further investigations. In recent years major progress has been achieved in the identification of modifiable factors relevant for primary prevention of PD. Well-supported factors include physical activity, adherence to a Mediterranean diet, and caffeine or tea consumption as protective factors, as well as pesticide exposure as a relevant risk factor. Advances in early and prodromal diagnosis of PD have opened new perspectives for secondary prevention. Earlier identification of individuals at risk may enable timely interventions aimed at attenuating early disease progression. However, despite this progress, the systematic implementation of early therapeutic interventions in the prodromal phase remains limited. Evidence is sparse and largely indirect, mainly inferred from later disease onset associated with physical activity and dietary patterns. Similarly, although early diagnosis and treatment of cognitive impairment are clearly recommended by clinical guidelines, they remain insufficiently integrated into routine clinical care. Finally, tertiary prevention strategies are supported by a broad evidence base. Multidisciplinary rehabilitative care models have demonstrated clear benefits in preventing complications, maintaining daily functioning and quality of life. While such rehabilitative approaches are widely implemented, the strong evidence supporting moderate- to high-intensity physical exercise remains insufficiently translated into routine practice. Looking ahead, a key goal for the coming decades is the development of personalized prevention strategies, including beyond other insights into gene-environment interactions and the integration of multi-omics data to tailor interventions to individual risk profiles. Such approaches hold promise to maximize preventive efficacy and reduce the overall burden of PD and related movement disorders.

Parkinson's disease (PD) risk and progression are influenced by a complex interplay of genetic, environmental, and internal factors. Environmental exposures have been understudied, primarily because of the associated complexity and inherent measurement challenges. The exposome framework, encompassing lifetime environmental exposures and biological responses, offers a way to better characterize these influences. The exposome embraces the "biography-to-biology" transition, encompassing general and specific external and internal exposures accumulating over the lifespan, and interacting with genetic factors. In other fields, machine learning has been applied to develop polyexposure scores to quantify cumulative environmental risks, although challenges remain in exposure measurement, latency, and disease heterogeneity. Advancing PD research requires refined exposome definitions, systematic data integration, validation, and collaboration to improve prediction, prevention, and personalized therapies. © 2026 International Parkinson and Movement Disorder Society.

Cognitive domains are central to diagnosing cognitive impairment in people with Parkinson’s disease (PwPD), yet are defined by expert consensus and cross-sectional data that assume temporal stability. This study examined whether cognitive domains remain stable or reorganize dynamically over time in PwPD. Using dynamic exploratory graph analysis, we analyzed 19 cognitive test scores from 355 PwPD across four yearly assessments (24,372 data points) from the DEMPARK/LANDSCAPE-study to identify dynamic organization of cognitive dimensions. Panel graphical vector autoregression models assessed dynamic couplings among dimensions. Five dynamic cognitive dimensions emerged, diverging substantially from theoretical domains and cross-sectional dimensions at baseline. Dynamic coupling revealed a temporal separation between card-sorting/cognitive flexibility and visuoconstruction. Cognitive domains in PwPD reorganize over time rather than remaining stable, challenging the static assumption of diagnostic criteria. Using PD as an exemplar, findings demonstrate the need for dynamic frameworks potentially revealing condition-specific temporal architectures when applied to other neurodegenerative disorders.

The prevalence of Parkinson’s disease (PD) is increasing globally and to date there is no disease-modifying pharmacological treatment. In recent years, however, a solid evidence base has been established that lifestyle changes, including physical activity and Mediterranean diet, can have a disease-modifying effect. Nevertheless, there are currently no standardized lifestyle intervention programs and the opinion of PD patients on lifestyle changes as a possible form of therapy is not clear. Therefore, the aim of this study was to investigate whether PD patients consider lifestyle changes to be relevant for their disease, and which hindering and supporting factors they describe when implementing preventive measures. Patients were recruited from two German neurology clinics. A standardized questionnaire was used to evaluate the patients’ perception of education and implementation of lifestyle changes. The study included 107 PD patients. Most patients stated that they tried to implement recommendations on lifestyle changes (n = 89, 85

Parkinson's disease (PD) has been historically defined as a disease of striatal dopamine deficiency secondary to degeneration of dopaminergic neurons in the substantia nigra pars compacta, related to the presence of Lewy bodies and Lewy neurites. Since the discovery of pathogenic variants in the gene encoding α-synuclein, as well as the finding that α-synuclein is a major constituent of Lewy pathology, PD is considered as a prototypical synucleinopathy. However, neuropathological studies consistently show that most people with PD display copathologies, many of which are linked to specific clinical features and outcomes. In this review, we summarize the spectrum and frequency of these co- and multi-pathologies in idiopathic and genetic PD and their impact on disease initiation and progression. Additionally, we also discuss how this multi-pathological landscape may impact biomarker research and the implementation of emerging disease-modifying therapies. © 2026 The Author(s). Movement Disorders published by Wiley Periodicals LLC on behalf of International Parkinson and Movement Disorder Society.

People with Lewy body disease exhibit heterogeneous clinical symptoms, diverse patterns of neurodegeneration on imaging and variable Lewy body pathology at post-mortem. The brain-first versus body-first (BvB) model provides a unifying framework that may account for much of this variability. According to the BvB model, Lewy pathology originates either in autonomic nerves of the gut or other peripheral neurons (body first) or in the olfactory bulb with subsequent spread to the limbic system (brain first). Both subtypes are thought to begin largely outside the CNS, possibly triggered by exogenous factors such as infectious agents or toxins. The model is supported by several observations. First, some individuals develop autonomic dysfunction and sleep disorders years before diagnosis, whereas other individuals experience these symptoms only after diagnosis. Second, in people with prodromal sleep disorders, cardiac sympathetic denervation precedes nigrostriatal degeneration by approximately a decade, whereas in individuals without sleep disorders, these systems degenerate in the opposite sequence. Third, post-mortem studies often reveal bottom-up or top-down gradients of Lewy pathology, consistent with body-first versus olfactory-first origins. This Review provides a critical appraisal of the BvB model, highlighting supporting evidence and current limitations. The article also considers implications for diagnostics, therapy and prevention, and outlines key avenues for future research.

This study examines the relationship between speech representations and the hierarchical structure of cognitive assessment in mild cognitive impairment. Utilizing 5,754 German neuropsychological assessment recordings, we evaluate six cognitive tasks across three score levels: task, domain, and global levels. We compare hand-crafted acoustic features with self-supervised learning (SSL) embeddings. Results show that although SSL representations generally outperform hand-crafted features at lower levels, this trend reverses for MCI classification. Furthermore, task-specific constraints influence performance: tasks with greater response freedom exhibit performance dilution as hierarchical levels increase, suggesting “specialist” representations, whereas the performance of highly structured tasks increases toward higher levels, suggesting “generalist” representations. These findings show links between task constraints and assessment hierarchy in automated clinical speech analysis.

The process of ageing is extremely variable in progression and phenotypic features including significant variations in disease milestones, such as cognitive impairment, frailty, or recurrent falls. Our aim was to analyze the influence of lifestyle factors on motor and cognitive performance in a longitudinal ageing study in older people on healthy ageing. We conducted a longitudinal analysis in a cohort of 744 older participants (mean 70 years) over an 8-year period. Cognitive performance was assessed using the Consortium to Establish a Registry for Alzheimer's Disease (CERADplus) test battery, including the Trail Making Test (TMT) for executive function. Gait performance was evaluated by measuring gait velocity. Dual-task performance was assessed by measuring gait velocity while checking boxes. Body Mass Index (BMI) was also recorded. Symptoms of depression were examined using Beck's Depression Inventory (BDI-II). We observed higher cognitive functions in individuals adhering to a high-frequency physical activity regimen and a resilient plant-based diet. Additionally, these individuals exhibited lower BDI-II scores and experienced mitigated cognitive decline. Participants who combined high physical activity, a high intake of plant-based foods, and extensive education-referred to as having a high "successful ageing index" -maintained nearly constant CERADplus total scores over the 8-year period. Protective lifestyle factors are linked to better cognitive and motor performance and a slower decline in cognitive function, indicating healthy ageing. Since the factors diet and exercise are modifiable, adopting them may enhance cognitive performance and autonomy in older adults.

Background Development of objective, reliable and easy-to-use methods to detect the onset of motor changes in Parkinson's disease (PD) is required to identify the temporal window in which neuromodulatory therapies could be implemented. Turning impairments are present at early stages of PD. However, it is unclear, to date, whether circular walking is also altered in prodromal PD. Objective Explore the predictive potential of circular walking in prodromal PD. Methods We included 102 subjects from a nine-year prospective cohort study (with 712 participants) in the current nested case-control analysis: 16 diagnosed with PD during follow-up (incident PD) and 96 healthy controls, matched in gender, age, and education with a 1:6 ratio. Forty-one gait features were extracted from baseline assessments with accelerometers under single and dual-tasking conditions. A Cox proportional hazards regression analysis was used to test the temporal association of non-correlated gait features to the probability of being diagnosed with PD. Results We identified associations between time from baseline measurement to PD diagnosis for eleven gait features, mostly based on harmonic ratios, step and stride variability, and index of harmonicity, partially in combination with gait speed. Most significant associations indicated that low gait symmetry and low rhythmicity were associated with larger hazard of being diagnosed with PD. Area under the curve ranged 0.63-0.69. Conclusions Despite low sensitivity and specificity, the findings potentially reflect prodromal motor impairments of PD manifested during circular walking, assessed quantitatively with a low-cost and wearable instrument. This will contribute to the characterization of pre-diagnostic PD motor symptoms.

Introduction:Unipolar depression is a frequent psychiatric disorder and associated with cognitive and motor deficits. It is also a prodromal or risk marker for various neurodegenerative diseases. Little research has been done on the extent to which motor and cognitive deficits persist in remitted depressive episode, and to what extent these deficits can be progressive. Methods:A total of 401 healthy subjects of the Tübingen TREND study aged between 50 and 80 years were examined over 6 years at intervals of 2 years. Of those, 81 had a positive history of unipolar depression (Dep+) and 320 had not (Dep-). We ruled out currently depressive participants. Mini-Mental-State Examination (MMSE), Consortium to Establish a Registry for Alzheimer's disease (CERAD), the motor part of the Movement disorder society-revised version of the Unified Parkinson disease rating scale (MDS-UPDRS III), gait speed, and dual tasking parameters were compared between groups. Results:Dep+ had lower gait velocity than Dep-. No significant change in parameters was found over the observed time. Discussion:Reduced gait speed in Dep+ may have potential as a diagnostic and prognostic marker for Dep- if confirmed in further studies. The lack of progression of all studied parameters over 6 years specifically in Dep+ argues against a relevant potential of this approach to define prodromal neurodegenerative cohorts by history of depression.

Parkinson's disease (PD) is marked by motor symptoms and often accompanied by mild cognitive impairment (PD-MCI), affecting up to 50% of patients and preceding PD dementia (PDD). Genetic factors may influence this progression, yet the underlying mechanisms remain unclear. This study investigated genetic factors influencing the progression from PD-MCI to PDD using polygenic risk scores (PRS). A genome-wide association study (GWAS) was conducted using data from the LANDSCAPE study. Multivariable Cox regression, Kaplan-Meier survival analysis, and concordance statistics assessed the relationship between PRS and PDD progression. No significant association was found between PD PRS and the risk of developing PDD.

Background: Primary angiitis of the central nervous system (PACNS) is a rare vasculitis affecting CNS blood vessels, posing diagnostic challenges due to the limited specificity of the established diagnostic tools. Neurofilament light chain (NfL) might be a promising biomarker in PACNS. Methods: NfL in serum and CSF was measured in 33 PACNS patients (25 active [aPACNS], 8 in remission [rPACNS]) enrolled between 2014 and 2022 and compared to controls (serum: n = 303; CSF: n = 68); Results: Serum NfL was significantly elevated in aPACNS (median: 45.77 pg/mL) versus rPACNS (6.68 pg/mL; p < 0.001) and healthy controls (6.05 pg/mL; p < 0.001). Similarly, CSF NfL was significantly elevated in aPACNS (median: 4914.58 pg/mL) compared to rPACNS (301.19 pg/mL; p = 0.002) and controls (262.83 pg/mL; p < 0.001). Serum and CSF NfL were significantly correlated (r = 0.90, p < 0.001). Additionally, an association between elevated NfL and ischemic lesions was observed (serum: r = 0.59, p = 0.006; CSF: r = 0.43, p = 0.032). A subgroup analysis excluding stroke patients still revealed elevated NfL in 90% (CSF) and 50% (serum), with diminishing discriminatory power with older age. Conclusions: NfL holds potential as a biomarker for PACNS, in particular in younger patients.