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Emerging evidence indicates that sustainable lifestyle changes—such as increasing physical activity, adopting healthy dietary patterns, and managing stress—can provide symptomatic benefits and potentially slow neurodegeneration in Parkinson's disease. Combining these interventions could produce synergistic effects, addressing multiple aspects of the pathophysiology. Despite the challenges of long-term adherence, innovative approaches such as digital tools and personalised strategies can support sustained lifestyle modifications. Tailoring interventions to individual needs and cultural contexts is crucial, especially in diverse socioeconomic settings. Future research should focus on large-scale, long-term studies to better understand the disease-modifying potential of lifestyle interventions and explore the biological mechanisms underlying their benefits. Overall, integrating lifestyle modifications into routine care offers a promising, accessible avenue to improve quality of life and potentially alter the progression of Parkinson's disease.

Background Essential tremor (ET) is a common movement disorder characterized by heterogeneous features, though the rate and pattern of worsening are variable. Longitudinal data combining clinical and objective motor measures remain limited, resulting in uncertainty regarding trajectories and predictors of progression in ET. Methods Twenty‐two patients from a previously established ET/ET‐plus cohort underwent a third clinical and kinematic evaluation almost seven years after baseline. Kinematic analysis assessed postural, kinetic, rest tremor, and finger‐tapping performance. Longitudinal changes were evaluated using non‐parametric statistics and linear mixed‐effects models adjusting for clinical covariates. Results Over time, tremor worsened overall. Kinematic measures indicated a selective increase in kinetic tremor severity, while rest and postural tremor amplitude remained stable. Clinically, tremor spread to a greater number of body regions. Soft neurological signs increased over time and were associated with greater tremor spread. Cognitive performance showed only a mild decline, partly related to age and affective symptoms. Higher baseline tremor severity was associated with greater worsening of kinetic tremor, and lower baseline cognitive scores with changes in postural tremor. Conclusions ET progression is heterogeneous and often non‐linear. Kinematic measures were particularly sensitive in capturing worsening of kinetic tremor, the most disabling clinical feature. The accumulation of soft neurological signs and their association with tremor spread support the notion of ET‐plus as a more advanced disease stage with broader cerebral involvement. Independent of disease progression, there were strong aging‐related effects. Future multimodal longitudinal studies may clarify how aging interacts with disease trajectories in essential tremor. Long‐term follow‐up (almost 7 years) of an ET/ET‐plus cohort (n = 22) shows heterogeneous and partly non‐linear progression, with a contribution of aging to disease burden. Tremor spreads anatomically over time, with selective worsening of kinetic tremor and increasing burden of soft neurological signs. Quantitative kinematic assessment complements clinical evaluation, enabling sensitive characterization of disease trajectories.

We review recent evidence about the pathophysiology of essential tremor and tremor in Parkinson’s disease. We believe that a network perspective is necessary to understand this common neurological symptom, and that knowledge of cerebral network dysfunction in tremor disorders will help to develop new therapies. Both essential tremor and Parkinson’s tremor are associated with increased activity in the cerebellothalamocortical circuit. However, different pathophysiological mechanisms lead to tremulous activity within this circuit. In Parkinson’s disease, evidence suggests that dopaminergic dysfunction of the pallidum triggers increased activity in the cerebellothalamocortical circuit. In essential tremor, GABAergic dysfunction of the cerebellar dentate nucleus and brain stem, possibly caused by neurodegeneration in these regions, may lead to tremulous activity within the cerebellothalamocortical circuit. In both disorders, network parameters such as the strength and directionality of interregional coupling are crucially altered. Exciting new research uses these network parameters to develop network-based therapies, such as closed-loop deep brain stimulation and transcranial magnetic or direct current stimulation.

Parkinson’s disease (PD) is a neurodegenerative disorder with motor symptoms (e.g., bradykinesia, tremors) and non-motor symptoms (e.g., cognitive deficits). Symptom progression varies across individuals, possibly due to differences in the spread of disease pathology. This study investigates individual-level gray matter atrophy in PD patients compared to a reference cohort, modeling neurobiological trajectories to understand symptom progression. Using normative modeling, we mapped individual deviations in gray matter atrophy in PD patients (Personalized Parkinson Project, PPP; N = 408; 42% female) against a reference model (N = 58, 836) of non-diagnosed individuals. Gray matter atrophy was defined as negative deviations from the normative model in cortical thickness and subcortical volume at baseline and two-year follow-up. We correlated the deviations with clinical motor and cognitive symptoms at an individual level and compared changes across PD subtypes (mild-motor predominant, intermediate, and diffuse-malignant). Cross-sectionally, PD patients showed significant gray matter atrophy, which correlated with cognitive impairment. Longitudinally, cortical thinning and subcortical atrophy patterns showed variation amongst subtypes. Specifically, the diffuse-malignant subtype, which is characterized by more diffuse symptoms and faster clinical progression, exhibited pronounced cortical thinning and subcortical atrophy over time. In this paper, we have considered the deviation scores at three levels of granularity: cases vs. control, subtypes, and the individual level. While our findings show subgroup-level patterns of variability, they also provide a method for exploring individual-level metrics of disease progression, acknowledging that individuals may deviate from the predefined categories or groups and can exhibit large variability over time.

Sensor-based remote monitoring could help better track Parkinson’s disease (PD) progression, and measure patients’ response to putative disease-modifying therapeutic interventions. To be useful, the remotely-collected measurements should be valid, reliable, and sensitive to change, and people with PD must engage with the technology. We developed a smartwatch-based active assessment that enables unsupervised measurement of motor signs of PD. Participants with early-stage PD ( N  = 388, 64% men, average age 63) wore a smartwatch for a median of 390 days. Participants performed unsupervised motor tasks both in-clinic (once) and remotely (twice weekly for one year). Dropout rate was 5.4%. Median wear-time was 21.1 h/day, and 59% of per-protocol remote assessments were completed. Analytical validation was established for in-clinic measurements, which showed moderate-to-strong correlations with consensus MDS-UPDRS Part III ratings for rest tremor (⍴ = 0.70), bradykinesia (⍴ = −0.62), and gait (⍴ = −0.46). Test-retest reliability of remote measurements, aggregated monthly, was good-to-excellent (ICC = 0.75–0.96). Remote measurements were sensitive to the known effects of dopaminergic medication (on vs off Cohen’s d = 0.19–0.54). Of note, in-clinic assessments often did not reflect the patients’ typical status at home. This demonstrates the feasibility of smartwatch-based unsupervised active tests, and establishes the analytical validity of associated digital measurements. Weekly measurements provide a real-life distribution of disease severity, as it fluctuates longitudinally. Sensitivity to medication-induced change and improved reliability imply that these methods could help reduce sample sizes needed to demonstrate a response to therapeutic interventions or disease progression.

The striatum receives dense dopaminergic projections, making it a key region of the dopaminergic system. Its dysfunction has been implicated in various conditions including Parkinson’s disease (PD) and substance use disorder. However, the investigation of dopamine-specific functioning in humans is problematic as current MRI approaches are unable to differentiate between dopaminergic and other projections. Here, we demonstrate that ‘connectopic mapping’ – a novel approach for characterizing fine-grained, overlapping modes of functional connectivity – can be used to map dopaminergic projections in striatum. We applied connectopic mapping to resting-state functional MRI data of the Human Connectome Project (population cohort; N = 839) and selected the second-order striatal connectivity mode for further analyses. We first validated its specificity to dopaminergic projections by demonstrating a high spatial correlation ( r = 0.884) with dopamine transporter availability – a marker of dopaminergic projections – derived from DaT SPECT scans of 209 healthy controls. Next, we obtained the subject-specific second-order modes from 20 controls and 39 PD patients scanned under placebo and under dopamine replacement therapy (L-DOPA), and show that our proposed dopaminergic marker tracks PD diagnosis, symptom severity, and sensitivity to L-DOPA. Finally, across 30 daily alcohol users and 38 daily smokers, we establish strong associations with self-reported alcohol and nicotine use. Our findings provide evidence that the second-order mode of functional connectivity in striatum maps onto dopaminergic projections, tracks inter-individual differences in PD symptom severity and L-DOPA sensitivity, and exhibits strong associations with levels of nicotine and alcohol use, thereby offering a new biomarker for dopamine-related (dys)function in the human brain.

Many Parkinson’s disease (PD) patients notice that motor symptoms worsen during stress, and experience stress-related neuropsychiatric symptoms such as anxiety and depression. Here we investigated which personal and disease characteristics are associated with perceived stress in PD, which PD symptoms are sensitive to stress, and we assessed self-reported benefits of stress-reducing strategies such as mindfulness. We sent an online survey to the Fox Insight cohort (n = 28,385 PD patients, n = 11,413 healthy controls). The survey included specific questions about the influence of stress on PD symptoms, use of stress-reducing strategies, and several validated scales measuring perceived stress, anxiety, dispositional mindfulness, rumination, and self-compassion. We received completed surveys from 5000 PD patients and 1292 controls. Patients perceived more stress than controls. Among patients, stress was correlated with increased rumination (R = 0.65), lower quality of life (R = −0.56), lower self-compassion (R = −0.65), and lower dispositional mindfulness (R = −0.48). Furthermore, patients indicated that stress significantly worsened both motor symptoms – especially tremor – and non-motor symptoms. Physical exercise was most frequently used to reduce stress (83.1%). Mindfulness was practiced by 38.7% of PD respondents, who noticed improvement in both motor and non-motor symptoms. Among non-users, 43.4% were interested in gaining mindfulness skills. We conclude that PD patients experience greater levels of stress than controls, and that stress worsens both motor and non-motor symptoms. Mindfulness may improve PD symptom severity, with the strongest effects on anxiety and depressed mood. These findings justify further controlled studies to establish the merits of mindfulness and other stress-alleviating interventions.

Tremor occurs in various forms across diverse neurological disorders, including Parkinson’s disease and essential tremor. While clinically heterogeneous, converging evidence suggests a shared brain network may underlie tremor across conditions. Here, we empirically define such a network using four modalities: lesion locations, atrophy patterns, EMG-fMRI, and deep brain stimulation outcomes. We show that network connectivity robustly explains clinical outcomes in independent cohorts undergoing deep brain stimulation of the subthalamic nucleus for Parkinson’s disease and the ventral intermediate nucleus for essential tremor. Maps from each cohort accounted for outcomes in the respective other, supporting a disorder-independent tremor network. A multimodal agreement map revealed consistent substrates in the primary motor cortex and motor cerebellum. To validate the network, we test its predictive power in a third, independent cohort treated with pallidal stimulation for Parkinson’s disease. Our findings define a robust, cross-condition tremor network that may guide both invasive and noninvasive neuromodulation strategies. Goede et al. combined multiple modalities to define a common tremor network across disorders. This finding may help optimize deep brain stimulation and guide future noninvasive therapies.

Background People with Parkinson’s disease (PD) are very sensitive to the effects of stress. The prevalence of stress-related neuropsychiatric symptoms is high, and acute stress worsens motor symptoms. Animal studies suggest that chronic stress may accelerate disease progression, but evidence for this in humans is lacking. Mindfulness-based interventions (MBIs) train participants to focus on the present moment, on purpose and without judgement. Previous studies suggest that MBIs may alleviate stress and reduce depression and anxiety in PD. We aim to demonstrate the efficacy of Mindfulness-Based Cognitive Therapy (MBCT) as a non-pharmacologic treatment strategy for neuropsychiatric (and motor) symptoms in PD, and to identify the mechanisms underlying stress and stress reduction in PD. Methods In a prospective randomized controlled trial (RCT), we investigate whether 8 weeks of MBCT, as compared to care as usual, can reduce symptoms of anxiety and depression in people with PD. We aim to include 124 PD patients, who experience mild-moderate symptoms of anxiety and depression, are eligible for magnetic resonance imaging (MRI) and naïve to mindfulness, and who have a disease duration ≤ 10 years. Every participant is followed for 12 months. Clinical and biochemical assessments take place at baseline (T0), after 2 months (T1), and after 12 months (T2); MRI assessments take place at T0 and T2. Our primary outcome is the total score on the Hospital Anxiety and Depression Scale (HADS) at T1, while correcting for the HADS score at T0, age, and gender. Beyond testing the effects of MBCT on symptoms of anxiety and depression in PD, we explore whether MBCT: (1) has an effect on motor symptom severity, (2) influences cerebral and biochemical markers of stress, and (3) leads to a change in biomarkers of PD progression. Discussion MIND-PD is one of the first RCTs with a 1-year follow-up to investigate the effects of MBCT on symptoms of anxiety and depression in PD, and to explore possible mechanisms underlying stress and stress reduction in PD. Insight into these mechanisms can pave the way to new treatment methods in the future. Trial registration ClinicalTrials.gov, NCT05779137. Registered on 12 January 2023.

Heterogeneity in Parkinson’s disease (PD) presents a barrier to understanding disease mechanisms and developing new treatments. This challenge may be partially overcome by stratifying patients into clinically meaningful subtypes. A recent subtyping scheme classifies de novo PD patients into three subtypes: mild-motor predominant, intermediate, or diffuse-malignant, based on motor impairment, cognitive function, rapid eye movement sleep behavior disorder (RBD) symptoms, and autonomic symptoms. We aimed to validate this approach in a large longitudinal cohort of early-to-moderate PD ( n  = 499) by assessing the influence of subtyping on clinical characteristics at baseline and on two-year progression. Compared to mild-motor predominant patients (42%), diffuse-malignant patients (12%) showed involvement of more clinical domains, more diffuse hypokinetic-rigid motor symptoms (decreased lateralization and hand/foot focality), and faster two-year progression. These findings extend the classification of diffuse-malignant and mild-motor predominant subtypes to early-to-moderate PD and suggest that different pathophysiological mechanisms (focal versus diffuse cerebral propagation) may underlie distinct subtype classifications.