Parkinson’s disease (PD) was described almost a century ago but has proven to be intractable in terms of curative therapies. Early detection and interventions for slowing down the progressively debilitating changes are the principal medical approaches to treat this problem. Tremor, loss of motor control and rigidity in limbs are the principal symptoms of Parkinson’s disease.

The paradox is that by the time these overt symptoms develop and a confirmed diagnosis is arrived at based on them, the patient’s motor abilities are already significantly compromised. The loss of motor control results into loss of personal independence altering the quality of life considerably. Therefore the search for early symptoms of Parkinson’s disease which precede loss of motor functions is a vital topic in current neuroscience research.

A long-term research study, known as the Honolulu-Asia Aging Study (HAAS) has helped to shed some light on the development and early signs of Parkinson’s disease. In this study, 8,006 Japanese-American men were examined periodically for 40 years. From 1991, cases of Parkinson’s disease started emerging in this group. Patients were diagnosed as Parkinson’s patients based on the independent diagnoses provided by two neurologists. Brain autopsies have also been performed on deceased patients to ascertain the formation of incidental Lewy bodies — a characteristic cellular feature of Parkinson’s disease.

The study has helped to identify some behavioral patterns in patients that precede the motor symptoms of PD. Excessive day time sleepiness and loss of the sense of smell emerged as two characteristics of patients who developed PD later in life. Constipation was also identified as a feature that indicated greater risk for development of PD in this groups of patients.

Patients who developed PD also showed slower response to a computerized reaction test. In addition to the clinical diagnosis of PD, brain autopsies from people who recorded the slowest reaction times also showed development of incidental Lewy bodies. Since tests like the reaction time to a specific cognitive challenge can be quantified, it may be possible to identify threshold levels in the reaction time to separate the high-risk and low-risk patients. However, a detailed analysis of these results with an aim to identify a quantitative threshold has not been performed in this study.

All these behavioral abnormalities were assessed 7-8 years prior to death which is a sufficient time window to provide therapeutic interventions as well. The incidence of PD in patients was significantly higher when symptoms like constipation (less than one bowel movement a day) and slow reaction time to the computerized test were present simultaneously.

Blood hemoglobin levels may also turn out to be a diagnostic sign for early identification of PD. Normally, hemoglobin levels decline with age. However, in the HAAS study, individuals who had greater than or equal to 16 mg/dl hemoglobin at age 71-75 years were more likely to develop Parkinson’s disease when assessed at age 80 years. Increased levels of iron in blood has been known to be associated with PD.

Are these symptoms definitive? These symptoms are certainly not as black and white as other diagnostic tests which measure specific levels of biochemical markers of a disease. However, these signs and symptoms are of immense predictive value given that they are evident 7-8 years prior to development of motor disabilities and clinically identifiable progression of Parkinson’s disease. Moreover the actual incidence of PD in patients from the HAAS study, which have presented these symptoms, has been confirmed by looking for Lewy bodies in brain sections which is a clear symptom of Parkinson’s disease. These researchers have concluded that presence of a combination of these symptoms — loss of sense of smell, constipation, slower reaction time, high hemoglobin levels and excessive daytime sleepiness — increases the risk for developing PD subsequently.

Even if these symptoms are only indicative and not definitive signs of PD, they can alert physicians to the possibility of incipient PD in geriatric patients and provide a time window for intervention before motor control is lost.

References

Ross GW, Abbott RD, Petrovitch H, Tanner CM, & White LR (2012). Pre-motor features of Parkinson’s disease: the Honolulu-Asia Aging Study experience. Parkinsonism & related disorders, 18 Suppl 1 PMID: 22166434

Abbott RD, Ross GW, Tanner CM, Andersen JK, Masaki KH, Rodriguez BL, White LR, & Petrovitch H (2012). Late-life hemoglobin and the incidence of Parkinson’s disease. Neurobiology of aging, 33 (5), 914-20 PMID: 20709430

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