Prevalence of Parkinsonian Signs and Associated Mortality in a Community Population of Older People
David A. Bennett, M.D., Laurel A. Beckett, Ph.D., Anne M. Murray, M.D., M.Sc., Kathleen M. Shannon, M.D., Christopher G. Goetz, M.D., David M. Pilgrim, M.D., and Denis A. Evans, M.D.
Background Older people frequently have signs of parkinsonism,but information about the prevalence of parkinsonism and mortalityamong those with the condition in the community is limited.
Methods A stratified random sample of 467 residents of EastBoston, Massachusetts, 65 years of age or older, were givenstructured neurologic examinations. Using uniform, specifiedcombinations of parkinsonian signs, we estimated the prevalenceof four categories of signs — bradykinesia, gait disturbance,rigidity, and tremor — and of parkinsonism, defined asthe presence of two or more categories. We did not study Parkinson'sdisease because it could not be distinguished from other conditionsthat can cause parkinsonism. Proportional-hazards models wereused to compare the risk of death among people with and thosewithout parkinsonism.
Results One hundred fifty-nine persons had parkinsonism, 301did not, and 7 could not be classified. The overall prevalenceestimates were 14.9 percent for people 65 to 74 years of age,29.5 percent for those 75 to 84, and 52.4 percent for those85 and older. With a mean follow-up period of 9.2 years, 124persons with parkinsonism (78 percent) and 146 persons withoutit (49 percent) died. Adjusted for age and sex, the overallrisk of death among people with parkinsonism was 2.0 (95 percentconfidence interval, 1.6 to 2.6) times that among people withoutit. Among people with parkinsonism, the presence of gait disturbancewas associated with an increased risk of death.
Conclusions Parkinsonism is very common among people over theage of 65, and its prevalence increases markedly with age. Parkinsonismis associated with a twofold increase in the risk of death,which is strongly related to the presence of a gait disturbance.
Signs of parkinsonism1,2,3 are frequently found on neurologicexamination of older people.4,5,6,7,8,9 Although these signsare often considered to be benign concomitants of aging,10,11data regarding their prevalence and relation to mortality arederived primarily from studies conducted in people who havecome to medical attention.12,13,14,15,16,17 Because the proportionof all the people with parkinsonism who come to medical attentionis unknown and may be small, such studies are unlikely to capturethe full spectrum of parkinsonism in the general population.There have been few population-based studies of parkinsonism.18
We estimated the prevalence of parkinsonian signs assessed bya structured neurologic examination as part of a community studyof common health problems of older people. Using uniform, specifiedcombinations of parkinsonian signs, we estimated the prevalenceof four categories of signs — designated as bradykinesia,gait disturbance, rigidity, and tremor — and of parkinsonism,which was defined as the presence of two or more categories.Over a nine-year period, we examined the relation between parkinsonismat the base-line clinical evaluation and subsequent mortality.We could not determine the prevalence of Parkinson's diseaseor mortality associated with it because our study design didnot allow us to distinguish this condition from others thatcause parkinsonism, such as Alzheimer's disease, subcorticalvascular disease, and multisystem atrophy.
Methods
Subjects
Participants were residents of East Boston, Massachusetts, anurban community of 32,000 people, and were 65 years of age orolder when the study began. The community is primarily composedof low- and middle-income working-class people, many of Italian-Americandescent. East Boston is one of the four centers of the NationalInstitute on Aging's Established Populations for EpidemiologicStudies of the Elderly project.19 The study was approved bythe Committee for the Protection of Subjects from Research Risksat Brigham and Women's Hospital, Boston, and all participantsprovided written informed consent.
Study Design
A complete door-to-door census of the community was carriedout in 1982–1984. All residents 65 years of age or olderwere asked to participate in a structured interview that assessedcommon medical and social problems of older people. Of the 4485community residents 65 or older, 3622 (80.8 percent) participated.The interview included brief tests of immediate and delayedmemory.20,21 A random sample of 714 persons, stratified accordingto age, sex, and memory performance, with older groups sampledmore heavily, was identified for a detailed clinical evaluation;54 of them died before being invited to be evaluated. Beginningin 1984 (an average of 16 months after the initial interview),467 of the 660 surviving eligible people (70.8 percent) underwentstructured neurologic examinations, neuropsychological performancetesting, and laboratory testing; in addition, for each participant,all medications were identified, a medical history was taken,and an interview was conducted with an informant who knew theparticipant well. This sample has been used previously to estimatethe prevalence of Alzheimer's disease and neurologic-examinationfindings in the community and the relation of Alzheimer's diseaseto mortality; more details of the study design and samplingprocedures have been reported previously.22,23,24
Clinical Evaluation
Most evaluations were performed by one board-certified neurologist.The medical history included the identification of all medicationsused to treat Parkinson's disease. A complete neurologic examinationwas performed, including a uniform, structured assessment ofparkinsonian signs. Cranial nerves, extremity strength, deep-tendonreflexes, extensor plantar responses, abnormal movements, frontal-releasingsigns, praxis, and position sensation and vibratory sensationin the feet were also tested. A diagnosis of Parkinson's diseasewas based on the clinician's judgment and required paucity ofmovements of both face and extremities, an abnormal gait witha reduced arm swing, slowed finger taps, and the absence ofweakness and other corticospinal tract signs; other parkinsoniansigns were supportive but not obligatory. A diagnosis of Alzheimer'sdisease satisfied the criteria of the National Institute ofNeurological and Communicative Disorders and Stroke and theAlzheimer's Disease and Related Disorders Association.25 Thecontent of the clinical evaluations and the diagnostic classificationsof participants have been described previously.23,26
Assessment of Parkinsonian Signs, Sign Categories, and Parkinsonism
A uniform, structured neurologic examination was used to determinethe presence of 12 individual parkinsonian signs. Parkinsoniansigns were sorted into four categories of motor signs of parkinsonism:bradykinesia (paucity of movements of the extremities and faceand slow finger taps), gait disturbance (shuffling gait, reducedarm swing, and prolonged turning), rigidity (in each extremity),and tremor (resting and postural). Postural-reflex impairmentwas not explicitly tested. To minimize the effect of an isolatedpoor performance on the clinical classification of parkinsonism,two or more signs within the category were required to be presentfor a patient to be considered to have a parkinsonian-sign category(with the exception of the tremor category, for which therewas only one sign of resting tremor and one of postural tremor).Parkinsonism was defined as the presence of two or more parkinsonian-signcategories1,2,3 (Table 1).
Table 1. The Specified Combinations of 12 Parkinsonian Signs Used to Define Four Parkinsonian-Sign Categories and Parkinsonism.
Statistical Analysis
We calculated estimates of age-specific prevalences for parkinsoniansigns, sign categories, and parkinsonism using a two-step procedure,as previously described.22 Prevalences were estimated for eachsex and age group from a logistic-regression model based onthe clinical-evaluation sample. These estimates were then weightedto adjust for unequal sampling from the East Boston populationand combined to give estimates for 10-year age groups. Testsfor a trend in prevalence with increasing age were based onthe coefficient for age in the logistic-regression model usedto obtain smoothed prevalence estimates in the first step.
The primary end point was death from any cause. Complete follow-updata on vital status were available through December 31, 1992.Information about deaths was obtained by systematic review ofthe National Death Index and from interviews with knowledgeableinformants. For secondary analyses, a trained researcher, blindedto data on parkinsonism, reviewed death certificates to determinethe underlying and immediate causes of death. These were codedaccording to the International Classification of Diseases, 9thRevision, Clinical Modification (ICD-9-CM).27 The analysis includedparticipants whose deaths were due to any respiratory disease(ICD-9-CM codes 460 to 519), chronic obstructive airway disease(codes 490 to 496), pneumonia (codes 480 to 487, and 507), anycardiovascular disease (codes 390 to 459), any cerebrovasculardisease (codes 430 to 438), any cancer (codes 140 to 239), orinjury (ICD-9-CM "E" codes).
Proportional-hazards models were used to compare the relativerisk of death among people with parkinsonism with that amongunaffected people, with adjustments for age and sex.28 Thesemodels treated the log of the instantaneous rate of mortalityat each time point in the study, among those who had survivedat least that long since the clinical evaluation, as increasinglinearly with age for both men and women, but allowed men tohave different mortality rates overall. The model was validatedto ensure that the effect of parkinsonism on mortality was nota result of inadequate accounting for the relation of mortalityto age or of a clinical diagnosis of Alzheimer's disease.24To be sure that any association of parkinsonism with mortalitywas not partly an artifact of the sample design that would notbe evident in the whole population, separate logistic regressions,adjusted by pseudo–maximum-likelihood estimation for thesampling design, were carried out, with survival at successiveyears of follow-up used as the outcome.29 This analysis wasconsistent with proportional-hazards models and showed similarrisks of death throughout the entire study period. Similar modelswere used for secondary analyses. Kaplan–Meier curveswere used to display the results.28
Results
Prevalence of Parkinsonian Signs and Sign Categories
Parkinsonian signs were common. The proportion of people witheach sign in each of the age groups is shown in Table 2. Percentageswere weighted to reflect the sampling design. The prevalenceof each parkinsonian sign except resting tremor increased significantlywith age.
Table 2. Age-Specific Estimates of the Prevalence of Parkinsonian Signs.
Factor analysis was used to assess the degree to which the associationsamong the 12 parkinsonian signs corresponded to the specifiedgroupings.30 four factors were identified that, in general,supported the placing of motor signs in the four categoriesof bradykinesia, gait disturbance, rigidity, and tremor (datanot shown). Therefore, the four sign categories were used insubsequent analyses. The number of people in whom each categorywas present and the prevalence (weighted to reflect the samplingdesign) of each sign category are given in Table 3. All signcategories were common, and their prevalence was strongly relatedto age. The prevalence of gait disturbance was higher in women;rigidity and tremor were more common in men.
Table 3. Age-Specific Estimates of the Prevalence of Parkinsonian-Sign Categories and Parkinsonism.
Prevalence of Parkinsonism
Of the 467 persons who were clinically evaluated, 159 had parkinsonismand 301 did not (7 could not be classified). The prevalenceof parkinsonism, weighted to reflect the sampling design, isshown in Table 3. Parkinsonism was very common, and its prevalenceincreased strongly with age but was unrelated to sex. The overallprevalence estimate for people 65 to 74 years of age was 14.9percent; this increased to 29.5 percent for those 75 to 84 andto 52.4 percent for those 85 and older.
Fifteen of the 159 persons with parkinsonism had a clinicaldiagnosis of Parkinson's disease. Seven of these were takinglevodopa.
Parkinsonism and Risk of Death
The average length of follow-up was 9.2 years. There were 276deaths — 124 of 159 persons with parkinsonism (78 percent),146 of 301 persons without parkinsonism (49 percent), and 6of 7 persons not classified. The crude association between adiagnosis of parkinsonism and death at any time during the follow-upperiod is shown, according to five-year age groups, in Table 4.In all age groups, the proportion of deaths was higher amongthose with parkinsonism.
Table 4. Crude Association between Parkinsonism and Death at Any Time during the Follow-up Period, According to Age Group.
We examined the risk of death associated with parkinsonism,adjusting simultaneously for the confounding effects of ageand sex. A proportional-hazards model was constructed that comparedthe risk of death among people with parkinsonism with that amongpeople without it. The overall risk of death among those withparkinsonism was 2.0 times that among those without it (95 percentconfidence interval, 1.6 to 2.6). Kaplan–Meier survivalcurves through eight years of follow-up are shown in Figure 1.When an indicator for Alzheimer's disease at the base-lineevaluation was included in the same model, the results werevirtually identical.
Figure 1. Kaplan–Meier Survival Curves for 159 Persons with Parkinsonism and 301 Persons without Parkinsonism through Eight Years of Follow-up.
To ensure that the complex stratified sampling did not distortthe relation between parkinsonism and mortality and that theresults based on the follow-up of the sample represented thepopulation, we carried out separate logistic-regression analysesat successive years of follow-up, using survival as the outcome.These analyses were consistent with the results of the proportional-hazardsmodel (data not shown). Secondary analyses based on the underlyingand immediate causes of death as coded according to the ICD-9-CMsuggested that the excess mortality among those with parkinsonismwas not due to any single group of diagnoses (data not shown).
Parkinsonian-Sign Categories and Risk of Death
Parkinsonism is a heterogeneous condition reflecting the occurrenceof various combinations of motor-sign categories. To examinethe association between the number of parkinsonian-sign categoriesand mortality, a model was constructed that included separateterms for two, three, and four sign categories. The risk ratiofor death for two categories was 1.9 (95 percent confidenceinterval, 1.4 to 2.5); it was 2.0 for three categories (95 percentconfidence interval, 1.3 to 3.0) and 2.6 (95 percent confidenceinterval, 1.4 to 4.8) for all four categories.
To assess the relation between individual sign categories andmortality, a proportional-hazards model was constructed thatincluded separate terms for each category. This model suggestedthat after adjustment for the other sign categories, only gaitdisturbance was associated with an increased risk of death.The risk ratio for bradykinesia was 1.3 (95 percent confidenceinterval, 0.9 to 1.7); for gait disturbance, 2.3 (95 percentconfidence interval, 1.7 to 3.1); for rigidity, 1.0 (95 percentconfidence interval, 0.7 to 1.3); and for tremor, 1.0 (95 percentconfidence interval, 0.8 to 1.3).
We then constructed a proportional-hazards model comparing therisk of death among people with parkinsonism who had gait disturbance,and the risk among those with parkinsonism without gait disturbance,with the risk among those without parkinsonism. As comparedwith those without parkinsonism, people with parkinsonism andgait disturbance had a relative risk of death of 2.4 (95 percentconfidence interval, 1.8 to 3.1; P<0.001); among those withparkinsonism without gait disturbance the relative risk was1.1 (95 percent confidence interval, 0.7 to 1.8; P = 0.716).Kaplan–Meier survival curves through eight years of follow-upare shown in Figure 2.
Figure 2. Kaplan–Meier Survival Curves for 159 Persons with Parkinsonism — 128 Who Had Gait Disturbance and 31 Who Did Not — and for 301 Persons without Parkinsonism through Eight Years of Follow-up.
In older persons, gait disturbance may be associated with manyconditions in addition to parkinsonism.31,32 Logistic regressionwas used to determine the extent to which gait disturbance wasassociated with each of the other sign categories. Among peoplewith gait disturbance, the odds ratios were as follows: forbradykinesia, 12.0 (95 percent confidence interval, 7.0 to 20.5;P<0.001); for rigidity, 1.8 (95 percent confidence interval,1.2 to 2.8; P<0.05); and for tremor, 2.2 (95 percent confidenceinterval, 1.4 to 3.6; P<0.001).
Discussion
These data suggest that parkinsonism is very common among peopleover the age of 65 and that its prevalence increases stronglywith age. Parkinsonism is associated with a twofold increasein the risk of death, which is strongly related to the presenceof a gait disturbance.
A previous population-based study, conducted in three municipalitiesin Sicily, examined age-specific prevalences of parkinsonism.18The authors reported a similar association with age, but lowerestimates for the prevalence of parkinsonism. They did not examinethe prevalence of individual parkinsonian signs or sign categories.Indirect evidence of the frequency of parkinsonian signs comesfrom population-based studies in the Washington Heights andInwood areas of New York City. These studies showed a slightlylower frequency of parkinsonian signs among people without overtneurologic disease who underwent detailed clinical evaluations.4Differences in definitions of parkinsonism between studies mayhave contributed to our higher prevalence estimates. The transitionto mild parkinsonism is gradual.33 In community settings, wheremild parkinsonism is likely to predominate, even small differencesin the distinction between the presence or absence of parkinsonismcould substantially affect estimates of prevalence.
Several studies have evaluated the risk of death associatedwith parkinsonism among people who came to medical attention.Hoehn and Yahr13 reported that, among people evaluated at aspecialty clinic, the risk of death associated with parkinsonismwas approximately three times that reported for the generalpopulation of the same age, race, and sex and that the riskof death was greater among those with manifestations of parkinsonismother than tremor. Three studies that identified people withparkinsonism or Parkinson's disease from medical registriesreported that the risk of death was between 1.6 and 2.6 timesthat of controls.12,16,17 Among people with Parkinson's disease,impaired gait and posture, assessed with the Webster scale,34were associated with increased mortality.17
Previous studies of people with Parkinson's disease who cameto medical attention suggest that such people are at greaterrisk of death from respiratory diseases,17 ischemic heart disease,16and cerebrovascular disease16 but are at a lower risk of deathfrom cancer.13 Our data did not show any differences in theimmediate or underlying causes of death on death certificatesbetween people with parkinsonism and those without it.
Two methodologic features of our study increase the reliabilityof the results. All the people from a geographically definedcommunity could be considered for participation, and the actualrates of participation and follow-up were high. We evaluatedparkinsonian signs as part of a structured general neurologicexamination and used specified combinations of parkinsoniansigns to document the presence of each sign category and todefine parkinsonism. Although it has infrequently been appliedto parkinsonism, this approach has been used successfully withother chronic neurologic conditions (e.g., cognitive impairment)and is generally considered to be more precise than global clinicalimpressions.35,36,37 In other studies, criteria for determiningthe presence or absence of parkinsonian-sign categories andparkinsonism were often not specified. Studies that rely onreviewing of medical records to determine the presence or absenceof parkinsonism may underestimate prevalence and overestimatemortality because people with mild parkinsonism may not seekmedical attention or their physicians may not diagnose theirparkinsonism.
Our study had several limitations. Parkinsonism may result fromseveral disorders that share common clinical features.31,38Our study design did not allow us to differentiate Parkinson'sdisease from other conditions that cause parkinsonism. Someof the parkinsonism we found probably represents mild, subclinicalParkinson's disease.32 Our finding that resting tremor had thelowest estimated prevalence of the 12 parkinsonian signs isnoteworthy; some investigators have suggested that the presenceof resting tremor is the most specific sign of Parkinson's disease.39,40
The motor examination did not correspond directly to scalesspecifically used to quantify motor function in Parkinson'sdisease.41,42 Some relevant parkinsonian signs were not explicitlyassessed. Postural-reflex impairment, rather than gait disturbance,is now used in studies of parkinsonism because gait disturbancemay be associated with many conditions other than parkinsonism,especially among older people.43,44 Several lines of reasoningsupport the gait-disturbance sign category as part of a parkinsoniansyndrome: the items in the neurologic examination were chosento reflect parkinsonism, factor analysis suggested that gaitdisturbance was strongly related to bradykinesia (data not shown),and logistic regression demonstrated that gait disturbance wasstrongly associated with each of the other sign categories.
We examined the relation to subsequent mortality of parkinsonismonly at the base-line evaluation. Since the prevalence of parkinsonismin older people appears to double with each additional decadeof life, parkinsonism is likely to develop before death in manypeople classified as not having the condition at base line.Other than the number of signs present, there was no measureof the severity of parkinsonism. The relative proportions ofmild, moderate, and severe parkinsonism could not be determined.It is likely that much of the parkinsonism was mild; this wouldbe consistent with population-based data for other chronic neurologicconditions.23 It is possible that the estimates of the prevalenceof parkinsonism would have been higher if people living in institutionshad been included.
Supported by the National Institute on Aging (contracts No1-AG-0-2107and NO1-AG-1-2106, cooperative agreement AG06789, and grantAG10161).
We are indebted to the residents of East Boston and to the staffof the East Boston Neighborhood Health Center for their cooperationand support; and to Dan Tancredi for statistical programmingand analyses.
Source Information
From the Rush Institute on Aging (D.A.B., L.A.B., A.M.M., D.A.E.) and the Department of Neurological Sciences (D.A.B., K.M.S., C.G.G.), Rush University and Rush–Presbyterian–St. Luke's Medical Center, Chicago; and the Harvard Community Health Plan, Boston (D.M.P.).
Address reprint requests to Dr. Bennett at the Rush Institute on Aging, 1645 W. Jackson Blvd., Suite 675, Chicago, IL 60612.
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