Original Research

Early and Accurate Identification of Parkinson Disease Among US Veterans

Early and accurate identification and management of veterans at risk for Parkinson disease is an important priority area for the US Department of Veterans Affairs because of the substantial impact on quality of life and disability-adjusted life years.

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Parkinson disease (PD) affects about 680,000 in the US, including > 110,000 veterans (Caroline Tanner, MD, PhD, unpublished data). 1 In the next 10 years, this number is expected to double, in part because of the aging of the US population. 1 Although the classic diagnostic criteria emphasize motor symptoms that include tremor, gait disturbance, and paucity of movement, there is increasing recognition that disease pathology begins decades before the development of motor impairment. 2

Pathologic studies confirm that by the onset of motor symptoms, at least 30% of nigrostriatal neurons are lost or dysfunctional. 3-5 Similarly, the Braak staging hypothesis posits initial deposition of Lewy bodies in the olfactory bulb and the dorsal motor nucleus of the vagus nerve, followed by prion-like spread through the brain stem into the midbrain/substantia nigra, and finally into the cortex (Figure 1). 6

The decades-long prodromal or preclinical phase represents a unique opportunity for early identification of those at highest risk for developing the motor symptoms of Parkinson disease. 7 Accurate identification, ideally before the onset of manifest motor disability, would not only improve prognostic counseling of veterans and families, but also could allow for early enrollment into trials of potentially disease-modifying therapeutic agents. Thus, early and accurate identification of PD is an important goal of the care of veterans with potential PD.

Prodromal Symptoms

Prodromal PD, as defined by the International Parkinson Disease and Movement Disorders Society (MDS), focuses on nonmotor symptoms that herald the onset of manifest motor PD. 8 The most commonly assessed nonmotor features include olfaction, constipation, sleep disturbance, and mood disorders.

Olfaction is impaired in > 90% of patients with motor PD at the time of diagnosis; by contrast, the prevalence of hyposmia in the general population ranges from 20% to 50%, with higher rates in older adults and in smokers. 9-11 Thus, olfaction appears to be a relatively sensitive, though nonspecific, prodromal feature. Importantly, subjective report of hyposmia is poorly reliable, so a number of different tests have been developed for objective assessment of olfactory dysfunction. 12 The 12-item Brief Smell Identification Test (B-SIT), derived from the longer University of Pennsylvania Smell Identification Test, is a “scratch-and-sniff” forced multiple choice test that can be self-administered by cooperative patients. 13,14 The B-SIT has been validated in multiple ethnic and cultural groups and shows high discrimination between PD subjects and controls. 13,15 Of note, olfactory impairment appears to be associated with risk of cognitive decline in PD, further emphasizing the need for accurate assessment to guide prognosis. 16

Like hyposmia, constipation can be noted long before the diagnosis of manifest motor PD. 17 After adjustment for lifestyle factors, constipated individuals have up to 4.5-fold increased odds of developing PD, and those with constipation suffer worsened disease outcomes and health-related quality of life. 17-20 Some groups have demonstrated alterations in gut microbiota of those with prodromal PD, which suggests local inflammatory processes and intestinal permeability may contribute to protein misfolding and disease development. 21,22 This also raises the intriguing possibility that dietary alterations may be neuroprotective or neurorestorative, although this has yet to be tested in humans. 23,24


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