Disturbed sleep in Parkinson's disease: anatomical and pathological correlates.
OBJECTIVE
Abnormal sleep is a common feature of Parkinson's disease (PD) and prodromal disorders of sleep are frequent (e.g. restless legs syndrome and rapid eye movement sleep behaviour disorder). However, the exact pathological basis of disturbed sleep remains as yet undefined.


METHODS
To investigate this further, 32 PD cases were stratified into three groups: (1) PD with disturbed sleep, PD(S); (2) PD with dementia (PDD) and disturbed sleep, PDD(S); and (3) PD without disturbed sleep, PD(nS). The extent of α-synuclein (αSyn) and Alzheimer disease (AD)-type pathology [amyloid β peptide (Aβ) and tau] was assessed in 15 regions of the PD brain.


RESULTS
The results demonstrate a significant association between disturbed sleep in PD and αSyn pathology in specific brainstem [locus coeruleus (P = 0.006) and raphe nuclei (P = 0.02)], hypothalamic [paramammillary nuclei (P = 0.04) and posterior nucleus (P = 0.02)], subcortical/limbic [amygdala (P = 0.03), thalamus (P = 0.01)] and cortical [entorhinal cortex (P = 0.01)] regions. A statistically significant increase of tau pathology was observed in the amygdala (P = 0.03), CA2 sector of the hippocampus (P = 0.01) and entorhinal cortex (P = 0.04) in PD cases with disturbed sleep.


CONCLUSIONS
Pathological changes in these structures, residing in the brain circuitry relating to sleep physiology, strongly predict the presence of sleep disturbances in PD.
Neuropathology Unit, Division of Brain Sciences, Department of Medicine, Imperial College London, London, UK.
M E
ME
Kalaitzakis
S M
SM
Gentleman
R K B
RK
Pearce
D000368:Aged; D000369:Aged, 80 and over; D016229:Amyloid beta-Peptides / Q000378:metabolism; D001921:Brain / Q000378:metabolism / Q000473:pathology*; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000378:metabolism / Q000473:pathology*; D012893:Sleep Wake Disorders / Q000378:metabolism / Q000473:pathology*; D051844:alpha-Synuclein / Q000378:metabolism; D016875:tau Proteins / Q000378:metabolism
D016229:Amyloid beta-Peptides; D051844:alpha-Synuclein; D016875:tau Proteins
Lewy body disease; Parkinson's disease; dementia; neuropathology; sleep