Association between mild parkinsonian signs and mild cognitive impairment in a community

Study population.

Participants were drawn by random sampling of healthy Medicare beneficiaries aged ≥65 years residing within a geographically defined area of northern Manhattan, NY. The cohort represents a combination of continuing members of a cohort originally recruited in 1992 and members of a new cohort recruited between 1999 and 2001, with approximately one-quarter of the sample from the original 1992 cohort and three-quarters from the new cohort. Recruitment of all participants was initially achieved by contacting a stratified random sample of 50% of all persons older than 65 years obtained from the Health Care Finance Administration (CMS: Center for Medicare Services). Potential participants were excluded if they did not speak English or Spanish. As of July 1, 2004, data were available on 2,776 participants who were evaluated between 1999 and 2001 (for the original 1992 cohort this represented their third follow-up assessment and for the new cohort this represented their baseline assessment). The mean age of the 2,776 participants was 78.2 ± 7.1 years, mean education was 9.9 ± 4.9 years, and 1,886 (67.9%) were women and 1,098 (39.6%) were Hispanic.

At the evaluation, demographic data were collected. Each participant also underwent a structured interview of health and function, which included a questionnaire about medical illnesses (e.g., arthritis, diabetes mellitus), and a standardized neurologic examination, which included an abbreviated (10-item) version of the motor portion of the Unified PD Rating Scale (UPDRS).⁸ We assigned a diagnosis of PD or Parkinson plus syndrome based on research criteria⁹ and participants were considered to have PD or Parkinson plus syndrome if 1) they had previously received a diagnosis of PD or Parkinson plus syndrome, or 2) they had two or more cardinal signs of parkinsonism on the standardized neurologic examination. Cardinal signs were bradykinesia, rigidity, postural instability, and rest tremor. For the diagnosis of PD or Parkinson plus syndrome, a cardinal sign was considered to be present when one UPDRS rating was ≥2. There were eight participants with one cardinal sign and either 1) increased tone in the setting of upper motor neuron signs (e.g., patients with a history of a symptomatic stroke with residual weakness or patients with MS) or 2) stooped posture due to severe musculoskeletal problems (e.g., kyphosis, scoliosis); these eight were not diagnosed with PD. Thirty-two (1.2%) participants had a diagnosis of PD or a Parkinson plus syndrome, which is consistent with a prevalence of PD that has been reported for persons ≥65 years of age in northern Manhattan.¹⁰ These 32 were excluded because our intention was to study a community population of older people without these diseases. We also excluded 330 (12.0%) of the remaining 2,744 participants because they had dementia. Participants with incomplete UPDRS data (n = 128) were excluded as well. Parkinsonian signs can result from the use of neuroleptic medications, but none of the remaining patients were taking these. Fifty-six were excluded because they had incomplete neuropsychological evaluations.

In total, 546 participants were excluded. The final sample, 2,230 participants, had a mean age of 77.2 ± 6.6 years, mean education of 10.3 ± 4.8 years, and 1,505 (67.5%) were women and 834 (37.4%) were Hispanic. The study was approved by our Institution’s Internal Review Board and written informed consent was obtained from all participants.

Neurologic evaluation.

As noted above, a standardized neurologic examination was conducted, including an abbreviated (10-item) version of the motor portion of the UPDRS.⁸ The 10 items were speech, facial expression, tremor at rest (in any body region), rigidity (rated separately in the neck, right arm, left arm, right leg, and left leg), posture, and body (axial) bradykinesia. Each of the ten items was rated from 0 to 4. A rating of 1 indicated a mild abnormality and a rating ≥2 indicated an abnormality of moderate or greater severity. A parkinsonian sign score (range = 0 [no parkinsonian signs] to 40 [maximum]) was calculated for each participant.

General medical doctors administered the modified motor portion of the UPDRS. These medical doctors were trained using a structured protocol, including 1) a 2-hour didactic session with a neurologist (E.D.L.) on physical findings in patients with parkinsonism and the administration and rating of the abbreviated motor portion of the UPDRS, 2) viewing a published UPDRS teaching videotape,¹¹ 3) rating the full motor UPDRS examination on four videotaped sample patients on the teaching videotape, and 4) feedback from the neurologist on their ratings. Inter-rater reliability of their ratings of the teaching videotape was substantial to excellent for each item (weighted kappa statistics for ratings were as follows: speech = 0.81, facial expression = 0.84, tremor at rest = 0.90, posture = 0.65, and axial bradykinesia = 0.87).

MPS were defined as present when any one of the following conditions was met: 1) two or more UPDRS ratings = 1 or 2) one UPDRS rating ≥2 or 3) the UPDRS rest tremor rating ≥1. The parkinsonian sign score was stratified into three subscores (axial function, rigidity, tremor) based on a factor analysis.¹² An abnormality in axial function was considered present when the participants had 1) UPDRS ratings = 1 in two or more of the four items of axial function (changes in speech, facial expression, posture, and axial bradykinesia) or 2) one UPDRS rating ≥2 in one the four items. An abnormality in rigidity was considered present when the participants had either 1) UPDRS ratings = 1 in two or more of the five items of rigidity (neck rigidity, right arm rigidity, left arm rigidity, right leg rigidity, left leg rigidity) or 2) one UPDRS rating ≥2 in one of the five items. Tremor was considered present when the participants had a UPDRS rest tremor rating ≥1.

All participants underwent a standardized neuropsychological battery.¹³ The neuropsychological battery was designed to assess cognitive functions that are typically affected in dementia¹³ and included measures of learning and memory, orientation, abstract reasoning, language, and visuospatial ability. Specific ability areas and tests administered include verbal list learning and memory (Selective Reminding Test),¹⁴ nonverbal memory (multiple choice version of the Benton Visual Retention Test [BVRT]),¹⁵ orientation (items from the Mini-Mental State Examination),¹⁶ verbal reasoning (Similarities subtest of the Wechsler Adult Intelligence Scale–Revised),¹⁷ nonverbal reasoning (Identities and Oddities subtest of the Mattis Dementia Rating Scale),¹⁸ naming (15-item version of the Boston Naming Test),¹⁹ letter fluency (Controlled Word Association),²⁰ category fluency (animals, food, and clothing, using procedures from the Boston Diagnostic Aphasia Examination [BDAE]),²¹ repetition (high-frequency phrases of the BDAE),²¹ auditory comprehension (first six items of the Complex Ideational Material subtest of the BDAE),²¹ visuoconstruction (Rosen Drawing Test),²² and visuoperceptual skills (multiple choice matching of figures from the BVRT).¹⁵

Participants were considered demented if they met established criteria,²³ including a disturbance of intellectual function that interfered with work or social activities, demonstrable impairment in memory based on neuropsychological testing, impairment in at least two other cognitive domains, and the absence of delirium. A designation of mild cognitive impairment (MCI) required 1) objective impairment in at least one of four cognitive domains (memory, executive function, language, visuospatial) based on performance on the neuropsychological test battery and a 1.5 SD cutoff for a domain score using normative corrections for age, years of education, ethnicity, and sex, 2) a subjective complaint of memory impairment, and 3) absence of functional impairment, according to published criteria.^24,25 Participants with MCI were stratified into those with 1) isolated impairment in memory or impairment in memory as well as one or more other cognitive domains (e.g., executive function, language, visuospatial) or 2) no impairment in memory but impairment in two or more other cognitive domains. These were designated as MCI with memory impairment (MCI+M) and MCI with no memory impairment (MCI-M).

Depressive symptoms were assessed and rated with a nine-item version of the Center for Epidemiologic Study Depression (CESD) scale,²⁶ in which individuals reported symptoms of depression (0 [no depressive symptoms] to 9 [maximal depressive symptoms]).

Statistical analyses.

Analyses were cross-sectional (SPSS version 11.0). Differences in categorical variables were assessed with χ² tests and differences in continuous variables with either t tests or analysis of variance (tables 1 and 2). A univariate logistic regression model was used to assess association between MCI+M (outcome = MCI+M vs no MCI, and excluding participants with MCI-M) and MPS. A similar univariate logistic regression model assessed the association between MCI-M (outcome = MCI-M vs no MCI, and excluding participants with MCI+M) and MPS. In multivariate logistic regression models, we included covariates if they were associated with both the dependent and independent variables (p < 0.01) or for which there was considerable a priori evidence that they were potential confounders. Putative confounders were age in years, sex, ethnicity (non-Hispanic white, Hispanic, non-Hispanic African American, and other), years of education, CESD score, smoker (ever vs never), and medical illnesses that were each coded as present vs absent by self-report (hypertension, diabetes mellitus, arrhythmia, congestive heart failure, peripheral vascular disease, stroke, arthritis, myocardial infarction, cancer, and chronic obstructive pulmonary disease). Finally, a cohort variable was included in these models to adjust for any cohort differences (original 1992 cohort vs 1999 to 2001 cohort).