דו״ח מאומת

Converging evidence from biopsychosocial research in humans and animals demonstrates that chronic sensory stimulation (via excessive screen exposure) affects brain development increasing the risk of cognitive, emotional, and behavioural disorders in adolescents and young adults. Emerging evidence suggests that some of these effects are similar to those seen in adults with symptoms of mild cognitive impairment (MCI) in the early stages of dementia, including impaired concentration, orientation, acquisition of recent memories (anterograde amnesia), recall of past memories (retrograde amnesia), social functioning, and self-care. Excessive screen time is known to alter gray matter and white volumes in the brain, increase the risk of mental disorders, and impair acquisition of memories and learning which are known risk factors for dementia. Chronic sensory overstimulation (i.e., excessive screen time) during brain development increases the risk of accelerated neurodegeneration in adulthood (i.e., amnesia, early onset dementia). This relationship is affected by several mediating/moderating factors (e.g., IQ decline, learning impairments and mental illness). We hypothesize that excessive screen exposure during critical periods of development in Generation Z will lead to mild cognitive impairments in early to middle adulthood resulting in substantially increased rates of early onset dementia in later adulthood. We predict that from 2060 to 2100, the rates of Alzheimer's disease and related dementias (ADRD) will increase significantly, far above the Centres for Disease Control (CDC) projected estimates of a two-fold increase, to upwards of a four-to-six-fold increase. The CDC estimates are based entirely on factors related to the age, sex, race and ethnicity of individuals born before 1950 who did not have access to mobile digital technology during critical periods of brain development. Compared to previous generations, the average 17-19-year-old spends approximately 6 hours a day on mobile digital devices (MDD) (smartphones, tablets, and laptop computers) whereas individuals born before 1950 at the same age spent zero. Our estimates include the documented effects of excessive screen time on individuals born after 1980, Millennials and Generation Z, who will be the majority of individuals ≥65 years old. An estimated 4-to-6-fold increase in rates of ADRD post-2060 will result in widespread societal and economic distress and the complete collapse of already overburdened healthcare systems in developed countries. Preventative measures must be set in place immediately including investments and interventions in public education, social policy, laws, and healthcare.…

PMID: 35164464

The association between exposure to particulates in polluted air and cognitive impairment is an emerging and significant health concern, particularly among younger populations. Although exposure to particulate matter ≤ 2.5 μm (PM_2.5) is linked with a lower estimated risk for dementia compared to traditional risk factors such as APOEɛ4 gene variants, the widespread and long-term population exposure to PM_2.5 pose substantial implications for public health. This review explores the sex differences in cognitive function induced by PM_2.5, which are age-dependent and distinct from the sex bias observed in Alzheimer's disease. In addition to biological sex and sex hormones, we also discuss the role of epigenetic regulation as a mechanism underlying sex-specific cognitive vulnerabilities to environmental toxins, particularly PM_2.5. Understanding these differences is important for developing targeted interventions and public health strategies to mitigate the cognitive impacts of PM_2.5 exposure.…

PMID: 41194168

Ageing, genetic, medical and lifestyle factors contribute to the risk of Alzheimer's disease and other dementias. Around a third of dementia cases are attributable to modifiable risk factors such as physical inactivity, smoking and hypertension. With the rising prevalence and lack of neuroprotective drugs, there is renewed focus on dementia prevention strategies across the lifespan. Neurologists encounter many people with risk factors for dementia and are frequently asked whether lifestyle changes may help. Exercise has emerged as a key intervention for influencing cognition positively, including reducing the risk of age-related cognitive decline and dementia. This article focuses on the current evidence for physical inactivity as a modifiable dementia risk factor and aims to support neurologists when discussing risk reduction.…

PMID: 31964800

Reaching the moderate-to-vigorous physical activity (MVPA) recommendations of 150 min/wk is difficult for older adults, particularly among those living with frailty and its associated risk of dementia. We examined the dose-response relationship between MVPA and dementia risk among at-risk persons living with and without frailty enrolled in the UK Biobank study. Survival analysis within a prospective cohort study. Participants at risk for all-cause dementia who wore an Axivity AX3 triaxial wrist-worn accelerometer between February 2013 and December 2015. MVPA was estimated from wrist-worn accelerometry in a subpopulation of the UK Biobank study. A modified version of the physical frailty phenotype was used to define frailty. Associations between MVPA dose (including interactions with frailty) and first-time incident dementia were analyzed using Cox regression models. MVPA was treated continuously and categorically across 5 levels to estimate the dose-response curve. Models were adjusted for demographics, frailty status, and comorbidities. This study included 89,667 adults (median age, 63 years; 56% women), with 735 participants developing dementia over an average of 4.4 years. Average weekly MVPA was 126 minutes. Each 30 minutes higher MVPA was associated with a 4% reduction in the risk of all-cause dementia (hazard ratio, 0.96; 95% CI, 0.93-0.99). The hazard ratios for engaging in 0-34.9, 35-69.9, 70-139.9, and ≥140 MVPA minutes per week were 0.59, 0.40, 0.37, and 0.31, respectively (P < .05 for all) compared with 0 MVPA minutes per week. All associations were similar across frailty status (interaction P for all models > .21). Our results suggest engaging in any additional amount of MVPA reduces dementia risk, with the highest benefit appearing among individuals with no MVPA. These associations are not substantially modified by frailty status.…

PMID: 39826907

<h4>Background</h4>Parkinson's disease (PD) is a progressive neurodegenerative disorder characterised by the degeneration of dopaminergic neurons in the substantia nigra pars compacta, resulting in motor symptoms such as tremor, rigidity and bradykinesia, along with cognitive impairments. While conventional research has largely focused on pathological degeneration, recent advances highlight the role of neuroplasticity-the brain's ability to reorganise and adapt neural circuits-as a potential mechanism for functional recovery and disease modification.<h4>Summary</h4>This review examines therapeutic strategies that enhance neuroplasticity in chronic Parkinson's disease mouse models. Key approaches discussed include neurotrophic factor (NTF) administration, deep brain stimulation (DBS), stem cell-based therapies and physical exercise. Evidence from experimental studies suggests that NTFs support dopaminergic neuron survival and synaptic repair, DBS modulates dysfunctional neural circuits and promotes adaptive plasticity, stem cell therapies offer both neuronal replacement and neurotrophic support, and physical exercise stimulates endogenous neuroplastic processes such as neurogenesis and synaptic reorganisation. Despite promising findings, variations in experimental design, disease severity and outcome measures across studies limit direct comparison and translation of results.<h4>Key message</h4>Neuroplasticity-based interventions represent a promising avenue for slowing disease progression and improving functional outcomes in Parkinson's disease. Integrating pharmacological, neuromodulatory and behavioural approaches may enhance therapeutic efficacy, though further research is required to standardise protocols and facilitate clinical translation.…

PMID: 41869462

PMID: PMC12982466

<b>Background:</b> Neurodegenerative diseases, including Alzheimer's disease and Parkinson's disease, are among the leading causes of disability and mortality worldwide. Dietary patterns have emerged as modifiable risk factors that may influence disease onset and progression. The Mediterranean diet (MedDiet), rich in fruits, vegetables, whole grains, legumes, fish, and extra virgin olive oil, has been consistently associated with better cognitive outcomes and reduced risk of neurodegeneration. <b>Aim:</b> This narrative review summarizes current evidence on the role of the MedDiet in slowing the progression of neurodegenerative diseases, with a particular focus on polyphenols such as resveratrol and oleuropein as key bioactive mediators. <b>Methods:</b> We synthesized findings from epidemiological studies, clinical trials, and mechanistic research to provide an integrated overview of how adherence to the MedDiet and its polyphenol components affects neurodegenerative disease trajectories. <b>Results:</b> Epidemiological studies suggest that higher MedDiet adherence is associated with slower cognitive decline, reduced conversion from mild cognitive impairment to Alzheimer's disease, and better motor and non-motor outcomes in Parkinson's disease. Mechanistically, the MedDiet modulates oxidative stress, neuroinflammation, mitochondrial function, vascular health, and the gut-brain axis. Polyphenols such as resveratrol and oleuropein exert neuroprotective effects through antioxidant activity, modulation of amyloid aggregation, mitochondrial biogenesis, and activation of signaling pathways (e.g., SIRT1). Clinical studies, although limited, indicate beneficial effects of polyphenol-rich interventions on cognitive and metabolic biomarkers. <b>Conclusions:</b> Current evidence supports the Mediterranean diet as a promising dietary strategy to slow the progression of neurodegenerative diseases. Polyphenols, including resveratrol and oleuropein, may play a role in mediating these effects. Further well-designed, long-term clinical trials are needed to establish causal relationships, optimize dosage, and explore biomarker-driven personalized nutrition approaches.…

PMID: 41470875

Neurodegenerative diseases, characterized by their insidious onset and progressive neuronal degeneration, present significant challenges in the fields of neuroscience and medicine. We elucidate the critical role of nutrition and cellular metabolism in the pathogenesis and progression of these disorders, with a particular focus on Alzheimer's disease (AD), Parkinson's disease (PD), and Huntington's disease (HD). We demonstrate that fundamental nutrients such as glucose, lipids, and amino acids are crucial for neuronal bioenergetics, oxidative stress mitigation, and neuroprotective functions. Furthermore, we emphasize the concept of metabolic reprogramming as a key driver in neurodegeneration; this process entails alterations in energy metabolism, mitochondrial dysfunctions, and shifts in nutrient utilization that exacerbate neuroinflammation and oxidative stress. We emphasize the potential advantages of nutritional strategies, especially those involving the Mediterranean dietary pattern, characterized by high antioxidant and omega-3 fatty acid content, to optimize cellular metabolic pathways and attenuate disease manifestations. However, clinical application of nutritional strategies faces several challenges including complexities surrounding nutrient mechanisms, patient adherence issues, and concerns regarding long-term efficacy. To address these obstacles, we advocate for personalized nutrition approaches that integrate metabolomics, genomics, and epigenetics to tailor interventions according to individual metabolic profiles. Additionally, emerging strategies such as probiotics along with synergistic combinations of nutrients and pharmaceuticals offer promising avenues for enhancing therapeutic outcomes. In conclusion, understanding the intricate interplay between nutrition and cellular metabolism is crucial for developing effective treatments for neurodegenerative diseases. Future research should prioritize mechanistic studies alongside precise assessment tools as well as high-quality clinical trials to validate the efficacy of these interventions.…

PMID: 41693955

More than 25 million people in the world today are affected by dementia, most suffering from Alzheimer's disease. In both developed and developing nations, Alzheimer's disease has had tremendous impact on the affected individuals, caregivers, and society. The etiological factors, other than older age and genetic susceptibility, remain to be determined. Nevertheless, increasing evidence strongly points to the potential risk roles of vascular risk factors and disorders (eg, cigarette smoking, midlife high blood pressure and obesity, diabetes, and cerebrovascular lesions) and the possible beneficial roles of psychosocial factors (eg, high education, active social engagement, physical exercise, and mentally stimulating activity) in the pathogenetic process and clinical manifestation of the dementing disorders. The long-term multidomain interventions toward the optimal control of multiple vascular risk factors and the maintenance of socially integrated lifestyles and mentally stimulating activities are expected to reduce the risk or postpone the clinical onset of dementia, including Alzheimer's disease. Hoy en día más de 25 millones de personas en el mundo están afectadas por demencia, la mayor parte con Enfermedad de Alzheimer. Tanto en los países desarrollados como en aquellos en vías de desarrollo, la Enfermedad de Alzheimer ha tenido un tremendo impacto en los individuos que la padecen, en los cuidadores y en la sociedad. Los factures etiológicos, más allá de la edad avanzada y la susceptibilidad genética, tienen que ser determinados. Sin embargo, hay una creciente evidencia que apunta fuertemente al papel potencialmente dañino de los factores de riesgo vascular y otros trastornos (fumar cigarrillos, presión alta y obesidad en la edad media de la vida, diabetes y lesiones cerebrovasculares) y al posible papel benéfico de los factores psicosociales (mayor escolaridad, participación social activa, ejercicio físico y actividades de estimulación mental) en el proceso patogénico y en las manifestaciones clínicas de las demencias. Se espéra que las intervenciones a largo plazo, desde múltiples áreas, orientadas al control óptimo de los múltiples factores de riesgo vascular y el mantenimiento de estilos de vida con buena integración social y actividades de estimulación mental reduzcan el riesgo o retarden la instalación de las demencias, incluyendo la Enfermedad de Alzheimer. Plus de 25 millions de personnes dans le monde sont aujourd'hui touchées par la démence, la plupart par la maladie d'Alzheimer. Cette maladie affecte de façon très importante les patients atteints, leurs soignants et la société qu'il s'agisse des pays développés ou en voie de développement. Les facteurs étiologiques autres qu'un âge avancé et une susceptibilité génétique restent à déterminer. Le rôle potentiel des facteurs de risque et des maladies vasculaires (tabagisme, hypertension artérielle et obésité de la quarantaine, diabète, lésions cérébrovasculaires) et l'éventuel rôle bénéfique des facteurs psychosociaux (niveau élevé d'éducation, engagement social actif, exercice physique, activité mentalement stimulante) sont cependant de plus en plus fortement mis en évidence dans le processus de la pathogenèse et les manifestations cliniques des troubles démentiels. Les interventions dans plusieurs domaines à long terme pour un contrôle optimal des multiples facteurs de risque vasculaire et le maintien d'un style de vie intégré socialement et d'activités mentalement stimulantes font espérer une réduction du risque ou un report du début clinique de la démence, y compris de la maladie d'Alzheimer.…

PMID: 19585947

A decade has passed since we published a comprehensive review in this journal addressing the topic of promoting successful cognitive aging, making this a good time to take stock of the field. Because there have been limited large-scale, randomized controlled trials, especially following individuals from middle age to late life, some experts have questioned whether recommendations can be legitimately offered about reducing the risk of cognitive decline and dementia. Despite uncertainties, clinicians often need to at least make provisional recommendations to patients based on the highest quality data available. Converging lines of evidence from epidemiological/cohort studies, animal/basic science studies, human proof-of-concept studies, and human intervention studies can provide guidance, highlighting strategies for enhancing cognitive reserve and preventing loss of cognitive capacity. Many of the suggestions made in 2010 have been supported by additional research. Importantly, there is a growing consensus among major health organizations about recommendations to mitigate cognitive decline and promote healthy cognitive aging. Regular physical activity and treatment of cardiovascular risk factors have been supported by all of these organizations. Most organizations have also embraced cognitively stimulating activities, a heart-healthy diet, smoking cessation, and countering metabolic syndrome. Other behaviors like regular social engagement, limiting alcohol use, stress management, getting adequate sleep, avoiding anticholinergic medications, addressing sensory deficits, and protecting the brain against physical and toxic damage also have been endorsed, although less consistently. In this update, we review the evidence for each of these recommendations and offer practical advice about behavior-change techniques to help patients adopt brain-healthy behaviors.…

PMID: 33935078