Clinical markers for identifying cholinergic deficits in Parkinson's disease.
BACKGROUND
Cholinergic projection systems degeneration is associated with dopamine nonresponsive features of Parkinson's disease (PD). Cholinergic deficits are variable in nondemented PD. Identification of cholinergic deficits in PD may help with selection of suitable patients for targeted cholinergic drug treatment in PD. The objective of this retrospective multivariate predictor analysis study was to identify clinical markers indicative of cholinergic deficits in PD patients, as assessed by acetylcholinesterase ([(11) C]PMP) positron emission tomography.


METHODS
One hundred thirty-seven PD patients (34 female) participated; median modified Hoehn and Yahr score was 2.5 (range, 1-4), average age 65.6 ± 7.4 years, and average duration of motor disease symptoms of 6.0 ± 4.2 years. Subjects were dichotomized as "normocholinergic" or "hypocholinergic" based on a 5(th) percentile cutoff from normal for the basal forebrain-cortical and pedunculopontine nucleus-thalamic cholinergic projection systems. Previously identified clinical indices of cholinergic denervation were used for statistical prediction of cholinergic deficits. Logistic regression determined which risk factors predicted cholinergic deficits. Sensitivity, specificity, and accuracy were determined for the (combinations of) significant predictor variables.


RESULTS
Forty-nine (35.8%) hypocholinergic PD subjects were identified. The combination of rapid eye movement (REM) sleep behavior disorder (RBD) symptoms and fall history showed highest diagnostic accuracy (81.1%) for predicting combined thalamic and cortical cholinergic deficits. A combined assessment of 8.5 m walk time and lower score on the Montreal cognitive assessment scale provided diagnostic accuracy of 80.7% for predicting isolated cortical cholinergic denervation.


CONCLUSIONS
Assessment of clinical indices of cholinergic denervation may be useful for identifying suitable subjects for trials of targeted cholinergic drug treatments in PD.
Department of Radiology, University of Michigan, Ann Arbor, Michigan, USA.
Martijn L T M
ML
Müller
Nicolaas I
NI
Bohnen
Vikas
V
Kotagal
Peter J H
PJ
Scott
Robert A
RA
Koeppe
Kirk A
KA
Frey
Roger L
RL
Albin
D000109:Acetylcholine / Q000378:metabolism*; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D015415:Biomarkers / Q000032:analysis; D059329:Cholinergic Neurons / Q000378:metabolism*; D004298:Dopamine / Q000378:metabolism; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D010300:Parkinson Disease / Q000175:diagnosis*; D049268:Positron-Emission Tomography / Q000379:methods; D020187:REM Sleep Behavior Disorder / Q000175:diagnosis*; D012189:Retrospective Studies
D015415:Biomarkers; D000109:Acetylcholine; D004298:Dopamine
PET; Parkinson's disease; acetylcholine; acetylcholinesterase; biomarkers