Olfactory dysfunction in pure autonomic failure: Implications for the pathogenesis of Lewy body diseases.
BACKGROUND
Pure autonomic failure (PAF) and Parkinson disease (PD) both are Lewy body diseases, and both entail substantia nigra dopaminergic, locus ceruleus noradrenergic, and cardiac sympathetic denervation. Multiple system atrophy (MSA) is a non-Lewy body disease in which alpha-synuclein accumulates in glial cells, with central catecholamine deficiency but preserved cardiac sympathetic innervation in most patients. PD is associated with more severe and consistent olfactory dysfunction than in MSA; whether PAF entails olfactory dysfunction has been unknown. In this study we assessed olfactory function in PAF in comparison with the two other synucleinopathies and whether olfactory dysfunction correlates with neuroimaging evidence of cardiac noradrenergic or nigrostriatal dopaminergic denervation.


METHODS
The University of Pennsylvania Smell Identification Test (UPSIT) was administered to 8 patients with PAF, 23 with PD, and 20 with MSA. 6-[(18)F]Fluorodopamine positron emission tomographic (PET) scanning was used to indicate cardiac noradrenergic innervation and the putamen:occipital cortex (PUT:OCC) and substantia nigra (SN):OCC ratios of 6-[(18)F]fluorodopa-derived radioactivity to indicate nigrostriatal dopaminergic innervation.


RESULTS
The PAF group had a low mean UPSIT score (22+/-3), similar to that in PD (20+/-2) and lower than in MSA (31+/-2, p=0.004). Individual UPSIT scores correlated positively with cardiac 6-[(18)F]fluorodopamine-derived radioactivity (r=0.63 in the septum, p<0.0001; r=0.64 in the free wall, p<0.0001) but not with PUT:OCC or SN:OCC ratios of 6-[(18)F]fluorodopa-derived radioactivity.


CONCLUSIONS
In synucleinopathies, olfactory dysfunction is related to Lewy body pathology and cardiac sympathetic denervation, independently of parkinsonism or striatal dopamine deficiency.
Goldstein
David S
DS
Clinical Neurocardiology Section, National Institute of Neurological Disorders and Stroke, National Institutes of Health, Bethesda, MD 20892-1620, USA. goldsteind@ninds.nih.gov
Sewell
LaToya
L
D000368:Aged; D001921:Brain / Q000000981:diagnostic imaging / Q000473:pathology; D004298:Dopamine / Q000031:analogs & derivatives; D005260:Female; D006801:Humans; D008297:Male; D008875:Middle Aged; D019578:Multiple System Atrophy / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D000857:Olfaction Disorders / Q000000981:diagnostic imaging / Q000209:etiology* / Q000473:pathology; D010300:Parkinson Disease / Q000150:complications / Q000000981:diagnostic imaging / Q000473:pathology; D049268:Positron-Emission Tomography / Q000379:methods; D054970:Pure Autonomic Failure / Q000150:complications* / Q000000981:diagnostic imaging / Q000473:pathology; D019275:Radiopharmaceuticals; D012720:Severity of Illness Index
D019275:Radiopharmaceuticals; D004298:Dopamine