Effects of essential tremor on longevity and mortality rates in families

Abstract

Essential Tremor (ET) is a common movement disorder characterized by action tremors, primarily affecting the hands and head. lthough previous studies have suggested potential links between ET and aging-related diseases, its relationship with longevity remains unclear, with conflicting evidence in the literature. To investigate this association, we analyzed data from 1,493 individuals across 145 families, encompassing both ET-positive (ET+) and ET-negative (ET-) participants. Using comprehensive statistical methods, including survival function estimation and regression modeling, we examined the potential influence of ET on lifespan. The median age of our participants was 67 years (IQR 54-77). Among deceased individuals, those with ET had a higher median age at death (80 years, IQR 70-86) compared to their ET- counterparts (70 years, IQR 59-77). Living ET+ participants also demonstrated slightly higher median ages (63 years, IQR 53-74) than living ET- individuals (60 years, IQR 49-71). Survival analysis revealed a significantly prolonged lifespan for ET+ individuals compared to ET- individuals (log-rank p = 1.11 × 10 ⁻23). Furthermore, hazard ratio (HR) calculations indicated a reduced risk of mortality for the ET+ group (HR = 0.44, CI95% = 0.37-0.52), particularly among males. These findings suggest that ET may be associated with increased longevity, though the underlying biological mechanisms remain unclear. Further research is essential to elucidate the processes contributing to this relationship and to explore its implications for understanding aging and neurodegenerative disorders.

Fig 1. Description of the cohort and comparison of median ages.

(A) Age distributions of ET+ and ET− individuals show a significant difference. (B) Analysis within the elderly cohort (age ≥  60) confirms significant age differences between ET+ and ET− groups. (C) Increase in median ages with disease severity, with statistically significant pairwise comparisons. (D) Effect of age of onset on median ages, with all pairwise comparisons statistically significant. (E) Age distributions within females and (F) males exhibit significant differences based on ET status. (G) Median ages of living ET+ and ET− cases show a slight difference. (H) No significant difference in median age was observed between those with and without clinical assessment in the entire cohort. ( * p <  0.05, ** p <  0.01, *** p <  0.001, **** p <  0.0001, not significant (ns): p >  0.05).

Fig 2. Comparison of median ages at death.

(A) Median age at death is significantly higher in ET+ cases (80 years) compared to ET− family members (70 years). (B) No significant difference in disease severity among ET+ patients. (C) Median ages at death significantly differ by disease onset, with specific pairwise comparisons showing statistical significance. (D) Significant difference in median ages at death between ET+ and ET− individuals by gender. (E) Median ages at death differ significantly based on clinical assessment. (F) Parkinsonism status (ET+PD+) does not significantly affect survival patterns. ( * p <  0.05, ** p <  0.01, *** p <  0.001, **** p <  0.0001, not significant (ns): p >  0.05).

Fig 3. Survival analysis of the cohort.

(A) Survival in patients with ET (red line) versus non-ET family members (blue line) in a univariate Cox Model, (B) Survival in ET (red line) versus non-ET (blue line) in a univariate Cox Model for elderly cohort, (C) Survival in females with (red line) versus males (blue line) in ET cohort in a univariate Cox Model, (D) Survival in females with (red line) versus males (blue line) in non-ET cohort in a univariate Cox Model, (E) Survival in males with ET (red line) and non-ET (blue line) in a multivariate Cox Model, (F) Survival in females with ET (red line) and non-ET (blue line) in a multivariate Cox Model. All groups except ET male vs female family members were significantly different at p <  0.0001 with increased hazard ratios (HR).

Fig 4. Family-based analysis.

The median and mean ages of ET patients and non-ET family members in families (A) Family-1, (B) -17, (C) -31, (D) -32, (E) -44, (F) -45, (G) -55, (H) -104, (I) -149 and (J) -161 were tested individually. Mean and median ages in ET patients were higher in seven families, but the differences were not significant (A) Family-1, (B) -17, (C) -31, (D) -32, (F) -45, (I) -149, (J) -161. In three families (E) -44, (G) -55, (H) -104 differences were significant ( * p <  0.05, ** p <  0.01, *** p <  0.001, **** p <  0.0001, not significant (ns): p >  0.05).