Background: The association between essential tremor (ET) and mortality risk remains uncertain. This study investigated the impact of episodic memory performance, measured through a word recall task, on mortality risk in ET within the Neurological Disorders in Central Spain (NEDICES) cohort, a population-based study of older adults. Methods: Participants were followed until death or 31 December 2017, and divided into four groups based on ET status and memory performance (errors in the 37-Minimental Examination’s three-word recall task). Cox proportional hazards models estimated mortality hazard ratios (HRs), and the Relative Excess Risk due to Interaction (RERI) assessed additive interactions. Results: Among 3998 participants, 3432 (85.8%) died over a median follow-up of 11.2 years. ET patients with episodic memory impairments had a higher mortality risk (HR = 1.25, 95% CI: 1.06–1.46) compared with controls with similar deficits (HR = 1.19, 95% CI: 1.09–1.28), whereas no significant increase was observed for ET patients without memory impairments (HR = 0.95, 95% CI: 0.74–1.21). RERI analysis revealed no significant additive interaction between ET and memory impairment (fully adjusted RERI: 0.11 [95% CI: −0.19–0.41]). Episodic memory impairments, regardless of ET status, were strongly associated with Alzheimer’s disease as a primary cause of death. Conclusions: These findings highlight the independent contribution of episodic memory impairment to increased mortality risk, with ET modestly amplifying this effect without significant interaction. Further research is needed to explore shared pathophysiological mechanisms between ET and neurodegenerative conditions.

The relationship between essential tremor (ET) and mortality risk remains uncertain. This study investigated the impact of episodic memory performance, measured through a word recall task, on mortality risk in ET within the NEDICES cohort, a population-based study of older adults. Participants were followed until death or December 31, 2017, and divided into four groups based on ET status and memory performance (errors in the 37-Minimental Examination’s three-word recall task). Cox proportional-hazards models estimated mortality hazard ratios (HRs), and the Relative Excess Risk due to Interaction (RERI) assessed additive interactions. Among 3,998 participants, 3,432 (85.8%) died over a median follow-up of 11.2 years. ET patients with episodic memory impairments had a higher mortality risk (HR = 1.25, 95% CI: 1.07–1.46) compared to controls with similar deficits (HR = 1.19, 95% CI: 1.09–1.28), whereas no significant increase was observed for ET patients without memory impairments (HR = 0.95, 95% CI: 0.75–1.21). RERI analysis revealed no significant additive interaction between ET and memory impairment (adjusted RERI: 0.11 [95% CI: -0.21–0.43]). Episodic memory impairments, regardless of ET status, were strongly associated with Alzheimer's disease as a primary cause of death. These findings highlight the independent contribution of episodic memory impairment to increased mortality risk, with ET modestly amplifying this effect without significant interaction. Further research is needed to explore shared pathophysiological mechanisms between ET and neurodegenerative conditions.

Background: Slowing of gait and daily activities, reported by older adults or by people close to them, may identify a clinically relevant motor phenotype in population-based movement-disorder epidemiology. We examined whether this simple baseline history item predicted long-term all-cause mortality in the Neurological Disorders in Central Spain (NEDICES) cohort. Methods: NEDICES was a prospective, population-based cohort of 5,278 census-based participants aged 65 years or older. Information on the slowing item was available for 3,994 participants. Reported slowing was defined as an affirmative answer to: 'Have you noticed, or has anyone told you, that lately you walk or do things more slowly?' Vital status and date of death were obtained through linkage to the Spanish National Population Register (Instituto Nacional de Estadística; INE). Follow-up accrued from baseline assessment to death or to administrative censoring on 31 December 2017 for participants who were alive. Survival was assessed with Kaplan-Meier curves and Cox proportional-hazards models. The multivariable model adjusted for age, sex, education, hypertension, prevalent tremor, prevalent Parkinson's disease, osteoarthritis, osteoporosis, smoking, alcohol consumption, depressive symptoms and/or antidepressant use, and comorbidity using a Carey-based index. Results: At baseline, 1,516 participants (38.0%) reported slowing. Through 31 December 2017, 3,426 deaths occurred, and 568 participants were censored alive. The mean observed time to death or censoring was 12.9 years (median 12.6 years). Crude mortality was higher among participants with reported slowing than among those without it (89.4% vs. 83.6%). Kaplan-Meier survival was shorter in the reported-slowing group (median: 140 vs. 158 months; log-rank p< 0.001). In the fully adjusted Cox model (n=3,841), reported slowing was independently associated with mortality (hazard ratio 1.09; 95% confidence interval 1.02-1.18; p=0.017). Conclusions: A single self- or informant-reported item on slowing of gait and daily activities identified older adults with a modest but independent excess long-term mortality risk.

Parkinson's disease (PD) is a prevalent neurodegenerative disorder in older adults, yet its long-term mortality impact remains inadequately defined. This study builds on prior findings from the Neurological Disorders in Central Spain (NEDICES) cohort, extending mortality analysis to a 23-year follow-up within a Spanish population-based sample. This prospective cohort study included 5,278 individuals aged 65 years and older. Conducted in two waves (baseline and follow-up), it identified 81 prevalent PD cases at baseline (1994-95) and 30 incident (premotor) cases at follow-up (1994-95). Mortality was tracked for up to 23 years, with Cox proportional hazard models used to estimate mortality hazard ratios (HRs), adjusted for demographic and clinical variables. Among 111 PD cases, 109 (98.2%) died during follow-up, compared to 4,440 (86.8%) of 5,114 without PD. PD was associated with a significantly increased mortality risk (adjusted HR=1.62; 95% confidence interval [CI]=1.31–2.01). Individuals with both PD and dementia had an even higher risk (HR=2.19; 95% CI=1.24–3.89). Younger-onset PD (<65 years) showed heightened mortality risk (HR=2.11; 95% CI=1.22–3.64). Cardiovascular or 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 individuals compared to the reference group (14.7% vs. 0.4%, p<0.001). PD significantly increases mortality risk over 23 years, particularly among those with early onset and dementia. These findings support a multidisciplinary PD care approach that addresses both motor and non-motor symptoms to improve long-term outcomes.

Background: Objective gait speed, self-rated walking pace, and self-reported walking difficulty are consistently associated with mortality. Far less is known about the prognostic meaning of perceiving, or being told, that one has recently become slower in both walking and everyday activities. We examined whether reported slowing was associated with long-term all-cause mortality in older adults. Methods: The Neurological Disorders in Central Spain (NEDICES) study is a prospective population-based cohort of 5278 adults aged 65 years or older. At baseline (1994–1995), participants were asked whether they noticed, or had been told, that lately they walked or did things more slowly; the item was available for 3994 participants. Vital status was ascertained through 31 December 2017 by linkage to the Spanish National Population Register. Kaplan–Meier methods and Cox regression were used. The primary model included the Carey-based comorbidity score and adjusted for demographic, movement-disorder, musculoskeletal, and lifestyle covariates. Results: Reported slowing was present in 1516 participants (38.0%); 3426 deaths occurred. In the primary complete-case model (n = 3858; 3311 deaths), reported slowing was associated with mortality after multivariable adjustment (hazard ratio 1.10, 95% confidence interval 1.02–1.18; p = 0.012). The item changed Harrell’s C-index from 0.7046 to 0.7048. The estimate was attenuated after excluding deaths within five years (1.08, 0.99–1.17; p = 0.087) and after exploratory adjustment for the Pfeffer Functional Activities Questionnaire score (1.08, 1.00–1.16; p = 0.055). Conclusions: Reported slowing in walking and everyday activities was associated with a modest increase in mortality after multivariable adjustment. It may serve as a simple indicator of slightly higher mortality risk, although its incremental contribution to individual-level prognostication was limited.

Background/Objectives: Toxic oil syndrome (TOS), caused by ingestion of adulterated rapeseed oil during Spain’s 1981 epidemic, remains associated with fatigue and cognitive dysfunction more than four decades later. No disease-specific treatment is established for these sequelae. We examined whether prefrontal repetitive transcranial magnetic stimulation (rTMS) was associated with changes in fatigue impact and related neurobehavioral outcomes. Methods: In this prospective open-label pilot study, 15 TOS survivors completed 20 high-frequency rTMS sessions targeting the left dorsolateral prefrontal cortex at F3 (10 Hz, 120% of resting motor threshold, 3000 pulses/session). Assessments were performed within seven days before and after treatment. The Fatigue Impact Scale for Daily Use (D-FIS) was the primary outcome. Secondary measures included the Beck Anxiety Inventory, Beck Depression Inventory-II, Pittsburgh Sleep Quality Index, Symbol Digit Modalities Test, Addenbrooke’s Cognitive Examination-III, and Trail Making Test. Paired changes were assessed using exact Wilcoxon signed-rank tests, Hedges gz, and false-discovery-rate correction. Results: Mean D-FIS decreased from 25.7 to 17.1 points (change, −8.6; 95% confidence interval, −12.8 to −4.6; p = 0.0012; gz = −0.96), with reductions in 12 participants. Anxiety and depression scores decreased by 11.4 and 10.1 points, respectively (both q = 0.0076). Sleep quality and sleep disturbances improved after adjustment. Addenbrooke’s scores increased by 8.2 points (q = 0.0076), and Trail Making Test B completion time decreased by 76.9 s (q = 0.0185). Conclusions: Prefrontal rTMS was followed by lower fatigue impact and improvement in selected secondary outcomes. The uncontrolled design precludes causal attribution; sham-controlled evaluation is warranted.