Profiling the most elderly parkinson's disease patients: Does age or disease duration matter?

Abstract

Despite our ageing populations, elderly patients are underrepresented in clinical research, and ageing research is often separate from that of Parkinson's disease (PD). To our knowledge, no previous study has focused on the most elderly ('old-old', age ≥ 85 years) patients with PD to reveal how age directly influences PD clinical progression. We compared the clinical characteristics and pharmacological profiles, including complications of levodopa treatment, disease progression, disabilities, and comorbidities of the old-old with those of comparable younger ('young-old', age 60-75 years) PD patients. In addition, within the old-old group, we compared those with a short disease duration (< 10 years at the time of diagnosis) to those with a long disease duration ≥10 years to investigate whether prognosis was related to disease progression or aging. This single-centre, case-control study compared 60 old-old to 92 young-old PD patients, matched for disease duration. Patients in the old-old group were also divided equally (30:30) into two subgroups (short and long disease duration) with the same mean age. We compared the groups based on several clinical measures using a conditional logistic regression. By study design, there were no differences between age groups when comparing disease duration, however, the proportion of men decreased with age (p = 0.002). At a comparable length of PD duration of 10 years, the old-old PD patients predominantly had significantly greater postural instability and gait disturbance (p = 0.006), higher motor scope of the Unified Parkinson's Disease Rating Scale (UPDRS-III, p<0.0001), and more advanced Hoehn & Yahr (H&Y) stage (p<0.0001). The Non-Motor Symptoms Questionnaire (NMSQuest) score was also significantly higher among the old-old (p<0.0001) compared to the young-old patients. Moreover, the distribution of NMS also differed between ages, with features of gastrointestinal problems (p<0.0001), urinary problems (p = 0.004), sleep disturbances and fatigue (p = 0.032), and cognitive impairment (p<0.0001) significantly more common in the old-old group, whereas sexual problems (p = 0.012), depression, and anxiety (p = 0.032) were more common in the young-old. No differences were found in visual hallucinations, cerebrovascular disease, and miscellaneous domains. While young-old PD patients received higher levodopa equivalent daily doses (p<0.0001) and developed a significant greater rate of dyskinesia (p = 0.002), no significant difference was observed in the rate of wearing-off (p = 0.378). Old-old patients also had greater disability, as measured by the Schwab and England scale (p<0.0001) and had greater milestone frequency specifically for dementia (p<0.0001), wheelchair placement (p<0.0001), nursing home placement (p = 0.019), and hospitalisation in the past 1 year (p = 0.05). Neither recurrent falls (p = 0.443) nor visual hallucinations (p = 0.607) were documented significantly more often in the old-old patients. Age and disease duration were independently associated with clinical presentation, course, and progression of PD. Age was the main predictor, but disease duration also had a strong effect, suggesting that factors of the ageing process beyond the disease process itself cause PD in the most elderly to be more severe.