Background: Parkinson’s disease (PD) is one of the most prevalent neurodegenerative disorders among older adults, yet its long-term impact on mortality within population-based cohorts remains insufficiently characterized. This study leverages data from the Neurological Disorders in Central Spain (NEDICES) cohort to provide a comprehensive 23-year mortality analysis in a Spanish population. Methods: In this prospective cohort study, 5278 individuals aged 65 years and older were evaluated across two waves: baseline (1994–1995) and follow-up (1997–1998). At baseline, 81 prevalent PD cases were identified, while 30 incident cases, likely in the premotor phase at baseline, were detected during follow-up. Mortality was tracked over 23 years, and Cox proportional hazard models were employed to estimate hazard ratios (HRs) for mortality, adjusting for relevant demographic and clinical variables. Results: Fifty-three individuals from the cohort in the reference group (without PD) were excluded due to unreliable mortality data. Among 111 PD cases, 109 (98.2%) died during follow-up compared to 4440 (86.8%) of 5114 without the disease. PD was associated with a significantly increased mortality risk (adjusted HR = 1.62; 95% confidence interval [CI] = 1.31–2.01). Patients with both PD and dementia had an even higher risk (HR = 2.19; 95% CI = 1.24–3.89). Early-onset PD (<65 years) showed heightened mortality risk (HR = 2.11; 95% CI = 1.22–3.64). Cardiovascular and cerebrovascular diseases were the leading causes of death in both PD and non-PD participants. PD was significantly more often listed as the primary cause of death in PD patients compared to the reference group (14.7% vs. 0.4%, p < 0.001). Conclusions: PD significantly increases mortality risk over 23 years, particularly among those with early onset and dementia. These findings underscore the importance of a multidisciplinary approach to PD care, targeting both motor and non-motor symptoms to enhance long-term outcomes.

Background: The new anti-amyloid therapies have brought the challenge of early and feasible identification of Alzheimer's disease (AD). Plasma biomarkers are promising tools, but real-world evidence remains limited. Objective: We aimed to evaluate the diagnostic performance of plasma core AD biomarkers, while accounting for potential confounding factors. Methods: Cross-sectional study of 285 patients (mean age 69.9 [range 50–85] years, 50.9% female) from five centers of the ReDeMa cohort. The diagnostic performance of plasma Aβ ₄₂ /Aβ ₄₀ , p-tau181, p-tau217, and p-tau217/Aβ ₄₂ was tested against cerebrospinal fluid (CSF) amyloid (A) and tau (T) pathology using a centralized, chemiluminescence-based platform (Lumipulse ^© ). The potential influence of comorbidities, medications, neuropsychological variables, and apolipoprotein E gene ( APOE ) ε4 allele was analyzed, and center-related variability was examined. Results: CSF amyloid (A+) was present in 216/285 (75.8%), while amyloid and tau pathology (A + T+) occurred in 191/283 (67.5%) patients. p-Tau217 displayed the best performance for detecting both A + (AUC 0.956) and A + T + (AUC 0.903). The optimal cutoff for A + was 0.234 pg/mL (95% CI 0.168–0.237), with an overall agreement of 95.8%. p-Tau217 performance showed some variability across centers (AUCs 0.916 to 1.000), but confidence intervals overlapped. APOE ε4 status ( r = 0.272), female sex ( r = 0.231), and cognitive performance ( r = −0.399) were associated with p-tau217, but multivariate models did not improve the diagnostic performance of p-tau217 alone. Significant associations were not found between p-tau217 and comorbidities or medications. Conclusions: Plasma p-tau217 is established as a first-choice biomarker for the early detection of AD pathology in specialized clinical settings, displaying excellent diagnostic accuracy and minimal site-related variability.

Background: Caring for individuals with mild cognitive impairment (MCI) is increasingly recognized as a significant clinical challenge. However, the latent burden, driven by perceived stigma and gender-specific vulnerabilities, remains poorly characterized during these early stages of cognitive decline. Objective: This study aimed to evaluate the prevalence of care partner strain and affiliate stigma, and to identify independent correlates of psychological distress and protective factors among informal care partners of individuals with MCI. Methods: We conducted a multicenter, observational, cross-sectional study across 19 memory clinics in Spain. Care partners (n = 196) were evaluated using the Zarit Burden Interview, Affiliate Stigma Scale, and validated instruments assessing resilience, relationship quality, coping strategies, and psychological distress. Multivariate logistic regression models identified independent predictors of burden and stigma. Results: Significant care partner strain affected 59.7% of the cohort, while 39.3% perceived themselves as stigmatized. Multivariate analysis revealed that high burden was independently associated with anxiety symptoms (OR = 1.13, p = 0.017) and perceived stigma (OR = 1.07, p = 0.007). High resilience served as the primary determinant protecting the 60.7% of partners who did not report significant stigma (OR = 1.05, p < 0.001). Compared to their male counterparts, female care partners were significantly younger and reported higher levels of burden, anxiety, and stigma. Conclusions: Care partner strain and affiliate stigma are correlated phenomena that emerge long before formal patient dependency. These findings underscore the need for gender-sensitive clinical frameworks and specific interventions that actively strengthen resilience immediately upon MCI diagnosis to mitigate early psychological deterioration.