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The Journals of Gerontology Series A: Biological Sciences and Medical Sciences 59:M864-M870 (2004)
© 2004 The Gerontological Society of America

A Longitudinal Study of Parkinsonism and Disability in a Community Population of Older People

Anne M. Murray1,, David A. Bennett2, Carlos F. Mendes de Leon2, Laurel A. Beckett3 and Denis A. Evans2

1 Division of Geriatrics, Hennepin County Medical Center, Minneapolis, Minnesota.
2 Rush Institute for Healthy Aging, Rush University, and Rush-Presbyterian-St. Luke's Medical Center, Chicago, Illinois.
3 Department of Epidemiology and Preventive Medicine, University of California–Davis.

Address correspondence to Anne M. Murray, MD, MSc, Geriatrics Division and Nephrology Analytical Services, Hennepin County Medical Center, 914 South 8th Street, Suite D-206, Minneapolis, MN 55404. E-mail: murra049{at}umn.edu


   Abstract
Top
 Abstract
Methods
 Results
 Discussion
 References
 
Background. Parkinsonian signs in patients without Parkinson's disease are often undetected but occur frequently in older people, and are often considered benign. We measured the association between parkinsonism and subsequent disability.

Methods. We conducted a prospective, longitudinal, community-based population study in East Boston, Massachusetts, using a stratified random sample of 455 community residents, aged 65 years and older. Four categories of parkinsonian signs were measured at baseline: bradykinesia, gait disturbance, rigidity, and tremor. Parkinsonism was defined as the presence of two or more categories of parkinsonian signs, and cases of Parkinson's disease were excluded from analyses. Disability was assessed annually over a mean of 4.7 years using the Katz, Rosow-Breslau, and Nagi disability measures.

Results. Parkinsonism at baseline strongly predicted subsequent disability as assessed with the three disability measures (on the Katz measure, ß = –1.30, p <.001). On average, a person with parkinsonism had a disability level at follow-up equal to that of a comparable person approximately 16.7 years for men and 8 years for women. The rate of developing disability for persons with parkinsonism increased each year; on the Katz measure, participants with parkinsonism declined on average 16.4% faster than those without. Gait impairment and bradykinesia strongly predicted subsequent disability; tremor and rigidity did not. The effect of parkinsonism was attenuated but still persistent in persons with coexistent moderate-to-severe cognitive impairment or stroke.

Conclusions. Parkinsonism strongly predicts progressive disability in the older community population and has a marked aging effect on disability level.

PARKINSONIAN signs such as bradykinesia, rigidity, tremor, and gait disturbance are commonly found on neurologic examination in older patients but are often considered to be benign indicators of aging in patients who have not been diagnosed with Parkinson's disease (1,2). In a previous study of a community population, however, we found the presence of two or more categories of parkinsonian signs to be associated with a twofold increased risk of death (3). Clinical cohort studies within Alzheimer's disease have found the presence of individual categories of parkinsonian signs in persons without diagnosed Parkinson's disease to be associated with increased morbidity and risk of entry into a nursing home (4,5).

Disability is a significant and costly public health problem (6), and is frequently attributed to multiple comorbidities (7–13). The role of parkinsonian signs in the development of disability, however, has received little attention. In this study, we examined the association of parkinsonian signs with disability in a longitudinal study of older residents in a community population.


   METHODS
Top
 Abstract
 Methods
Results
 Discussion
 References
 
Participants and Study Design
The study was conducted in the community of East Boston, Massachusetts, one of the four centers of the National Institute on Aging's Established Populations for Epidemiologic Studies of the Elderly (EPESE) project. Details of the East Boston study design have been previously published (14,15). Briefly, the study population consisted of all noninstitutionalized community residents aged 65 years or older who were identified during a door-to-door census conducted between 1982 and 1984. Of the 4485 eligible residents, 3809 (84.9%) participated in an in-home, baseline population interview to assess medical and social problems common to older people. The study was approved by the Committee for the Protection of Subjects from Research Risks at Brigham and Women's Hospital, Boston, and all participants provided written informed consent.

A random sample, stratified according to age, sex, and cognitive test performance, was drawn from the study population for detailed clinical evaluation. The present analysis is based on the random sample only. Of the 714 persons selected, 54 died before examinations could be arranged; 467 (70.8%) of the 660 survivors were evaluated. The other survivors declined the clinical evaluation. There was no significant difference in mean age, sex, level of disability, baseline blood pressure, or history of stroke, heart attack, or diabetes between the participants and the nonparticipants who declined the clinical evaluation (14). The clinical evaluation included a structured neurologic examination by one board-certified and two board-eligible neurologists, neuropsychological performance testing, and laboratory testing.

All participants were followed with annual interviews for up to 6 years, including those who moved from the community or entered nursing homes. The first (n = 467), second, fourth, and fifth follow-up interviews were conducted by telephone; the third and sixth, in the home. Follow-up participation at each interview ranged from 88% to 93% of survivors.

Assessment for Parkinsonian Signs
Parkinsonian signs were assessed using a uniform, structured neurologic examination. Participants were assessed for the presence of 12 extrapyramidal signs, divided into 4 categories of signs: 3 of bradykinesia (paucity of movements of the extremities and face, and slow finger taps), 3 of gait (shuffling gait, reduced arm swing, prolonged turning), 4 of rigidity (of each extremity), and 2 of tremor (resting, postural). Participants with essential tremor only were rated as "no resting or postural tremor." Individual categories of parkinsonian signs were defined as being present if half or more of the extrapyramidal signs within the category were present, i.e., 2 of 3 signs of bradykinesia, 2 of 3 signs of gait, 2 of 4 signs of rigidity, and 1 of 2 signs of tremor. For the purpose of this analysis, participants were classified as having parkinsonism if they had 2 or more categories of parkinsonian signs (bradykinesia, gait, rigidity, or tremor) (16,17).

Data from the clinical evaluation also were used for the classification of Parkinson's disease. In this study, the diagnosis of Parkinson's disease was based on the neurologist's judgment and required paucity of movements of both face and extremities, slowed finger taps, an abnormal gait with a reduced arm swing, and the absence of weakness and other corticospinal signs; other extrapyramidal signs were supportive but not required. Only 15 participants (3.3%) met the criteria for Parkinson's disease; 7 of those participants were taking levodopa. The neurologic examination also included assessment for dementia, stroke, amyotrophic lateral sclerosis, multiple sclerosis, and other less common chronic neurologic diseases. The diagnosis of Alzheimer's disease was made using the criteria of the National Institute of Neurological and Communicative Disorders and Stroke and the Alzheimer's Disease and Related Disorders Association (NINCDS/ADRDA) for probable Alzheimer's disease (18). Stroke was diagnosed by the neurologist on the basis of history and neurologic examination. Level of cognitive impairment was ascertained by the neurologist using examination and neuropsychological testing data and was assessed as none, mild, or moderate to severe.

Measures of Disability
Self-reported disability data were obtained as part of the yearly population interviews. The modified Katz Activities of Daily Living (ADL) Scale (19,20) was used to assess ability to perform each of six activities without help (bathing, dressing, transferring, walking across a room, eating, toileting). Three items from the Rosow-Breslau Functional Health Scale (21) were used to assess ability to walk one-half mile, climb stairs, and do heavy housework. Items developed by Nagi (22) were used to assess level of difficulty performing four basic physical functions: bending, stooping or crouching, pushing or pulling an object such as a chair, and reaching above the shoulders; little or no difficulty was coded as "not disabled" for that function. Each disability measure was summarized by calculating the number of items that the participant was able to perform. Higher scores indicated higher function and less disability. Because the clinical evaluation did not occur at the same time as the baseline population interview, baseline data on disability status were obtained from the population interview conducted on the date closest in time to the clinical evaluation. The mean interval between the clinical evaluation and disability measurements was approximately 2.2 ± 131.4 days. An average of 4.7 yearly interviews (range, 1–6 interviews) were available per participant.

Statistical Analyses
We first tested baseline differences in disability between participants with and without parkinsonism, using weighted t tests to adjust for the stratified sampling design of the clinical evaluation sample (SUDAAN software release 7.5; Research Triangle Institute, Research Triangle Park, NC). Subsequent models tested the association of baseline parkinsonism with disability during follow-up. Longitudinal disability data were fitted using repeated-measures regression models (23). We used a logistic link function to characterize the relation between predictor variables and disability outcomes, assuming a binomial error distribution of the outcome data. Each outcome was modeled as the proportion of activities a participant could perform by dividing the summary scores by the total number of items of each measure. Thus, the regression coefficients represent the linear effect of a predictor variable on the log odds of the proportion of nondisabled activities on each measure. A Generalized Estimating Equations (GEE) approach was used to fit the sequential outcome data, taking into account the correlated structure of disability data due to repeated assessment over time (SAS PROC GENMOD software release 6.12; SAS Institute, Cary, NC) (23,24). Missing observations, whether due to refusal or to death, were treated as missing completely at random in these analyses. The model also assumed that the score actually observed for a person reflected both consistent, unmeasured person-specific variability and also within-person, between-observation variability that was greatest for people near the middle of the disability scales. Residual analyses and graphical and analytic diagnostics were used to check the validity of the model assumptions. For graphical presentation, predicted proportions of nondisabled activities based on the covariates included in the model were recoded to the original scale by multiplying each proportion by the total number of items of each measure. Participants with Parkinson's disease diagnosed at the clinical evaluation (n = 15) were excluded from the study sample for all analyses; thus the modified sample size was 452 (467 minus 15).

Comorbidities likely to contribute to disability were measured by self-report or hospitalization records. A comorbidity index specific to this population was calculated by determining how many of the following five comorbidities were present at the baseline disability assessment: history of hypertension, diabetes, myocardial infarction, hip fracture, and cancer.

Disability outcome data across all yearly assessments were first modeled as a function of age at the time of interview, sex (male), and the interaction of age and sex. Participants with diagnosed Parkinson's disease (n = 15) at clinical evaluation were excluded from analyses. In the primary analysis, a term for parkinsonism was added to each model to test the degree to which participants with parkinsonism at baseline have higher levels of disability, averaged across all yearly interviews, adjusting for comorbidities. Next, to test the degree to which parkinsonism is associated with change in disability since baseline, an interaction term for follow-up time with parkinsonism was added in a longitudinal model. Secondary analyses examined the effect of the presence at baseline clinical evaluation of mild cognitive impairment, stroke, and moderate-to-severe cognitive impairment, and death during the follow-up period.


   RESULTS
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 Abstract
 Methods
 Results
Discussion
 References
 
After exclusion of the 15 participants with Parkinson's disease, the sample size was 452. The mean age of the sample at baseline was 80.5 ± 7.6 years, 44% were male, mean level of education was 6.8 ± 3.7 years, and mean number of Katz activities participants were able to perform was 5.27/6.0. Participants had a self-reported history of or previous hospitalization for the following comorbidities: myocardial infarction, 11.3%; hypertension, 28.3%; diabetes, 14.6%; hip fracture, 4.7%; and cancer, 10.8%.

At baseline, participants with parkinsonism reported significantly lower disability scores and thus greater levels of disability than those without parkinsonism, except for those aged 65 to 74 years for the Katz measure, and those aged 85 years and older for the Nagi measure (Table 1). After adjustment for age, sex, and comorbidity in the primary longitudinal analysis (using all available disability data), parkinsonism was significantly associated with disability (Table 2). This effect was consistent across all three measures of disability, indicating that participants with parkinsonism reported a lower proportion of activities they could do at each year of age than those without parkinsonism. The magnitude of the effect can be compared with that of age. For example, the effect of parkinsonism on Katz ADLs among women (ß = –1.30) was approximately 8 times the effect of age (ß = –0.163). Thus, a female participant with parkinsonism was estimated to have an ADL disability level similar to a female participant 8 years older. For male participants, the comparable age effect was more than double at 16.7 years. When indicators for mild cognitive impairment and number of days between the assessment for parkinsonism at the clinical evaluation and assessment of physical function were added separately to the primary model, the magnitude of the main effect of parkinsonism was unchanged.


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  		Table 1. Cross-Sectional Baseline Association Between Age Group, Parkinsonism, and Disability in a Stratified Random Sample of 65-Year-Old Residents of East Boston, Massachusetts.

 

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  		Table 2. ß Estimates of Independent Predictors of Disability Over an Average Follow-Up of 4.7 Years in a Stratified Random Sample of 65-Year-Old Residents of East Boston, Massachusetts.

 
A term for the interaction between parkinsonism and study observation time (lag time) was added to the primary models and revealed a highly significant negative interaction effect, indicating that parkinsonism was associated with a greater increase in disability during follow-up. On average, participants classified with parkinsonism declined 16.3%, 12.1%, and 10% faster on the Katz, Rosow-Breslau, and Nagi measures, respectively, than did comparable participants without parkinsonism (p <.001 for each comparison). Figure 1 illustrates the effects of parkinsonism on initial degree of disability and rate of decline among women, as assessed on the Katz measure. Each pair of curves shows the estimated trajectories, based on the model, for two women (one with parkinsonism, one without) of the same age at baseline and over a 5-year period. Plots for the Rosow-Breslau and Nagi measures and for men were similar, but the effect of parkinsonism on the trajectories of disability was less marked.



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  		Figure 1. Effects of parkinsonism on initial degree of disability and rate of decline among women, as assessed on the Katz measure. Each pair of curves shows the estimated trajectories, based on the model, for two women (one with parkinsonism, one without) of the same age at baseline and over a 5-year period

 
The analyses reported in Table 2 were repeated separately after exclusion of persons with stroke (n = 50) or moderate-to-severe cognitive impairment (n = 99) on clinical evaluation, for a reduced sample size of 303 participants. The effect of parkinsonism on disability was slightly to moderately attenuated but still significant (p <.02) for all groups and ages except for the Nagi measure (Table 3). Likewise, when participants who died during the follow-up period (n = 168) were excluded from the analysis to exclude the possibility that the functional decline may have been attributable to terminal decline, the effect of parkinsonism was attenuated but still significant (p <.01).


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  		Table 3. ß Estimates Showing Effects of Parkinsonism on Disability Over an Average Follow-Up of 4.7 Years in Subgroubs of a Stratified Random Sample of 65-Year-Old Residents of East Boston, Massachusetts.

 
To evaluate the relative importance of each of the four categories of parkinsonian signs (gait disturbance, bradykinesia, rigidity, and tremor) in predicting disability, the analyses reported in Table 2 were repeated, substituting each category of parkinsonian signs as a predictor. For the Katz measure, gait impairment and bradykinesia strongly predicted subsequent disability (p <.001); results for tremor and rigidity did not reach statistical significance. Similar findings were noted for the Rosow-Breslau and Nagi measures.

The importance of gait impairment as a predictor of disability raises the possibility of misclassification, or a tautology between the presence of parkinsonian gait and two of the disability items: walking across a small room on the Katz measure and walking one-half mile on the Rosow-Breslau measure. By redefining parkinsonism as the presence of two of three categories of parkinsonian signs excluding gait, we still a found strong association of parkinsonism with disability for all three disability measures, although the effects were attenuated compared with the original findings (ß = –0.70 [p <.002], –0.52 [p <.006], and –0.26 [p <.07] for the Katz, Rosow-Breslau, and Nagi measures, respectively). Conversely, by using our original definition of parkinsonism, and excluding walking-related items in the Katz and Rosow-Breslau measures, the associations were virtually the same as in the original models, suggesting that misclassification was unlikely.


   DISCUSSION
Top
 Abstract
 Methods
 Results
 Discussion
References
 
Parkinsonism, defined by the presence of two or more categories of parkinsonian signs, is associated with higher levels of reported disability at baseline and a marked increase in disability during follow-up. These findings are especially noteworthy because the persons in this study with Parkinson's disease were excluded from the analyses. The effect of parkinsonism was approximately the same as that of 8 years of aging among women, and approximately 16.7 years of aging among men. The association of parkinsonism with disability was consistent across different measures of disability, suggesting that this condition affects a relatively broad range of physical function, and was not modified by the addition of mild cognitive impairment or comorbidities to the model. The associations with disability outcomes were attenuated after exclusion of participants who had significant cognitive impairment or stroke or who died during the follow-up period, but the associations remained statistically robust. Thus, disability associated with parkinsonism does not seem to be primarily due to coexistence with other neurologic conditions common among older persons, or to terminal decline.

The use of a population-based, prospective, longitudinal study design with excellent follow-up enabled us to examine the association between parkinsonism and change in disability in this community population, without the risk of referral bias inherent in clinic population studies. Other strengths of this study include the uniform assessment of parkinsonian signs as part of a structured neurologic examination, the generalized linear model approach to describe the predicted change in disability associated with parkinsonism, and the use of three well-recognized and validated disability scales as measures of outcome. The availability of diagnoses of coexistent neurologic conditions, such as stroke and cognitive impairment, and comorbidities also allowed us to evaluate these conditions as confounders or modifiers of the observed effect.

We are not aware of previous studies that have examined the prospective relation of parkinsonian signs with disability in a community population in patients without diagnosed Parkinson's disease, although the association has been studied in clinical populations with Parkinson's disease (25–30). Although clinical cohort studies of Parkinson's disease do not capture the full spectrum of parkinsonian signs, our findings are consistent with these studies in that gait impairment and bradykinesia were usually found to be more strongly related to disability than to tremor and rigidity.

Our findings contribute to previous findings suggesting that parkinsonism is very common (1,2,31) and is associated with substantial morbidity and mortality (3,32,33). Previous research by our group in this community population found the prevalence of parkinsonism to be approximately 15% among those aged 65 to 74 years, 30% for those aged 75 to 84 years, and 52% for those aged 85 years and older (3). The high prevalence of parkinsonian signs and their substantial association with disability raises the possibility that parkinsonism is an important but largely unrecognized determinant of disability among community-dwelling older adults. In this sense, the presence of parkinsonian signs may represent a preclinical condition associated with disability. Parkinsonian signs as measured in our study are easily identifiable. Examining for the presence of bradykinesia and gait impairment in older patients could lead to early identification of those at risk for developing disability.

Persons with bradykinesia and gait disturbance may benefit from rehabilitation. Multiple reports in small study samples suggest that physical therapy may improve performance on the Unified Parkinson's Disease Rating Scale (UPDRS) (34) as well as ADL function, stride length, speed, and balance, beyond the effect of medication in patients with early-to-midstage Parkinson's disease (35–37). Additionally, previous studies have found that very frail older patients benefit from intensive rehabilitation to improve lower extremity function (38), and in-home interventions for frail elderly persons with disability decrease the progression of functional decline (39).

The pathophysiology of parkinsonism and its relation to disability has not been well studied in patients without Parkinson's disease. Although idiopathic Parkinson's disease is clearly related to dopamine deficiency in the substantia nigra, and, in patients with Alzheimer's disease, pathologic changes such as Lewy bodies and neurofibrillary changes in the substantia nigra have been found to be associated with parkinsonian signs (40–42), the pathogenesis of individual parkinsonian signs in persons without Alzheimer's disease is unknown. It may involve the same mechanism, or possibly cerebrovascular disease affecting the subcortical motor and/or nigrostriatal system. That microinfarctions may play a role is suggested by the Cardiovascular Health Study using magnetic resonance imaging scans, in which 33% of asymptomatic participants in the community population were found to have "silent" cerebral infarctions, most commonly found in the basal ganglia (43,44). Further research is needed to determine whether modifying cardiovascular risk factors such as diabetes and hypertension could decrease the risk and effect of parkinsonism on disability.

It is possible that progression of parkinsonism may be associated with more rapid functional decline. The natural history of the progression of parkinsonism was examined in a recent study (33), but further research is needed to examine the relation between progression of parkinsonism and progression of disability.

There are limitations to this study. The motor examination used in the neurologic examination did not directly correspond to the UPDRS because the UPDRS had not yet been devised, and severity of parkinsonian signs was not specifically measured. Although measures of gait were used, postural reflexes were not specifically tested, but it is unlikely that the addition of such measures would have changed the magnitude of the main effect of parkinsonism. Research by our group revealed that this same grouping of parkinsonian signs was consistent in a diverse sample of older persons and corresponds closely with the traditional UPDRS grouping of parkinsonian signs (45). The East Boston EPESE study and clinical evaluation data are also somewhat dated; thus, methods for identifying parkinsonism and Parkinson's disease, other neurologic diseases, and comorbidities may not have been as accurate or as sensitive as current methods. A recent study by our group in 787 older, well-educated nuns and priests, however, also found a very high prevalence of parkinsonism, with 95% having some motor signs on a modified UPDRS (33). Another limitation is that interrater reliability testing was not performed among the physicians conducting the neurologic examination; therefore, we could not estimate the degree to which misclassification of parkinsonism may have affected our results. However, given the strong and statistically robust associations between parkinsonism and disability, it is likely that even a modest degree of misclassification would not have substantially altered our findings. Finally, the mean age of our clinical evaluation sample was quite high and education level low, due in large part to the oversampling of older ages for purposes of the original study design (measurement of Alzheimer's disease). Thus, our results may not be generalizable to populations with a lower mean age and higher education level.

In spite of these limitations, our findings strongly suggest that parkinsonism, which is common in older individuals but often remains undetected, contributes significantly to disability in community-dwelling older adults.


   Acknowledgments
 
This work was supported by the National Institute on Aging Grant AG 10161 and Contracts N01-AG-12106 and N01-AG-02106.

We gratefully acknowledge the support of the staff of the East Boston Neighborhood Health Center. We are also indebted to Charles Owen, Dan Tancredi, and Linyun Zhou for statistical programming, Dr. David Knopman for his review of the manuscript, and James M. Kaufmann and Dana D. Knopic for manuscript preparation.

Received January 24, 2003

Accepted May 30, 2003


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 Results
 Discussion
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