Subjective Sleep Disturbance and Lewy Pathology: Data from a Cohort of Essential Tremor Brain Donors

Abstract

Introduction: Sleep disturbances have been associated with essential tremor (ET). However, their pathophysiological underpinnings remain unknown. In this exploratory study, we examined the association between subjective sleep disturbances and the presence of Lewy pathology (LP) on postmortem brain examination in ET cases.

Methods: Fifty-two ET cases enrolled in a prospective, longitudinal study were assessed over an average period of 42 months. Cases completed the Pittsburgh Sleep Quality Index (PSQI), which yields seven component scores (e.g., sleep quality, sleep latency). For each component score, we calculated the difference between the last score and the baseline score. Brains were harvested at death. Each had a complete neuropathological assessment, including extensive α-synuclein immunostaining. We examined the associations between baseline PSQI scores and the change in PSQI scores (last - first), and LP on postmortem brain examination.

Results: ET cases had a mean baseline age of 87.1 ± 4.8 years. LP was observed in 12 (23.1%) of 52 cases; in 7 of these 12, LP was observed in the locus coeruleus (LC). Change in time needed to fall asleep (last - first sleep latency component score) was associated with presence of LP on postmortem brain examination - greater increase in sleep latency was associated with higher odds of LP (odds ratio = 2.98, p = 0.02). The greatest increase in sleep latency was observed in cases with LP in the LC (p = 0.04).

Conclusion: In ET cases, increases in sleep latency over time could be a marker of underlying LP, especially in the LC.

Keywords: Essential tremor; Lewy pathology; Locus coeruleus; Pathophysiology; Sleep disturbance.

Fig. 1.

Study Sample Selection Flowchart.

Figure 2.. Mean of Sleep Latency Difference Score by LP Status.

LP: Lewy pathology; LC: Locus Coeruleus; No LP: ET cases with no LP. * P<0.05; *** P<0.001 Sleep Latency Difference Scores: Mean values are presented in the figure. The sleep latency difference scores were derived by subtracting the sleep latency component score at the baseline visit from the last reported score. Positive scores denote an increase in sleep latency, while negative scores signify a decrease in sleep latency.