Glenn T. Stebbins

Movement Disorder Society-Sponsored Revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Scale Presentation and Clinimetric Testing Results

We present a clinimetric assessment of the Movement Disorder Society (MDS)‐sponsored revision of the Unified Parkinsons Disease Rating Scale (MDS‐UPDRS). The MDS‐UDPRS Task Force revised and expanded the UPDRS using recommendations from a published critique. The MDS‐UPDRS has four parts, namely, I: Non‐motor Experiences of Daily Living; II: Motor Experiences of Daily Living; III: Motor Examination; IV: Motor Complications. Twenty questions are completed by the patient/caregiver. Item‐specific instructions and an appendix of complementary additional scales are provided. Movement disorder specialists and study coordinators administered the UPDRS (55 items) and MDS‐UPDRS (65 items) to 877 English speaking (78% non‐Latino Caucasian) patients with Parkinsons disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS‐UPDRS showed high internal consistency (Cronbachs alpha = 0.79–0.93 across parts) and correlated with the original UPDRS (ρ = 0.96). MDS‐UPDRS across‐part correlations ranged from 0.22 to 0.66. Reliable factor structures for each part were obtained (comparative fit index > 0.90 for each part), which support the use of sum scores for each part in preference to a total score of all parts. The combined clinimetric results of this study support the validity of the MDS‐UPDRS for rating PD.

Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: status and recommendations.

The Movement Disorder Society Task Force for Rating Scales for Parkinsons disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scales mixing of impairment and disability and its non‐linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2–4). Although a “modified HY scale” that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should “rate what you see” and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five‐point scales should be maintained.

Movement Disorder Society Task Force report on the Hoehn and Yahr staging scale: Status and recommendations The Movement Disorder Society Task Force on rating scales for Parkinson's disease

The Movement Disorder Society Task Force for Rating Scales for Parkinsons disease (PD) prepared a critique of the Hoehn and Yahr scale (HY). Strengths of the HY scale include its wide utilization and acceptance. Progressively higher stages correlate with neuroimaging studies of dopaminergic loss, and high correlations exist between the HY scale and some standardized scales of motor impairment, disability, and quality of life. Weaknesses include the scales mixing of impairment and disability and its non‐linearity. Because the HY scale is weighted heavily toward postural instability as the primary index of disease severity, it does not capture completely impairments or disability from other motor features of PD and gives no information on nonmotor problems. Direct clinimetric testing of the HY scale has been very limited, but the scale fulfills at least some criteria for reliability and validity, especially for the midranges of the scale (Stages 2–4). Although a “modified HY scale” that includes 0.5 increments has been adopted widely, no clinimetric data are available on this adaptation. The Task Force recommends that: (1) the HY scale be used in its original form for demographic presentation of patient groups; (2) when the HY scale is used for group description, medians and ranges should be reported and analysis of changes should use nonparametric methods; (3) in research settings, the HY scale is useful primarily for defining inclusion/exclusion criteria; (4) to retain simplicity, clinicians should “rate what you see” and therefore incorporate comorbidities when assigning a HY stage; and (5) because of the wide usage of the modified HY scale with 0.5 increments, this adaptation warrants clinimetric testing. Without such testing, however, the original five‐point scales should be maintained.

Movement Disorder Society-sponsored revision of the Unified Parkinson's Disease Rating Scale (MDS-UPDRS): Process, format, and clinimetric testing plan.

This article presents the revision process, major innovations, and clinimetric testing program for the Movement Disorder Society (MDS)–sponsored revision of the Unified Parkinsons Disease Rating Scale (UPDRS), known as the MDS‐UPDRS. The UPDRS is the most widely used scale for the clinical study of Parkinsons disease (PD). The MDS previously organized a critique of the UPDRS, which cited many strengths, but recommended revision of the scale to accommodate new advances and to resolve problematic areas. An MDS‐UPDRS committee prepared the revision using the recommendations of the published critique of the scale. Subcommittees developed new material that was reviewed by the entire committee. A 1‐day face‐to‐face committee meeting was organized to resolve areas of debate and to arrive at a working draft ready for clinimetric testing. The MDS‐UPDRS retains the UPDRS structure of four parts with a total summed score, but the parts have been modified to provide a section that integrates nonmotor elements of PD: I, Nonmotor Experiences of Daily Living; II, Motor Experiences of Daily Living; III, Motor Examination; and IV, Motor Complications. All items have five response options with uniform anchors of 0 = normal, 1 = slight, 2 = mild, 3 = moderate, and 4 = severe. Several questions in Part I and all of Part II are written as a patient/caregiver questionnaire, so that the total rater time should remain approximately 30 minutes. Detailed instructions for testing and data acquisition accompany the MDS‐UPDRS in order to increase uniform usage. Multiple language editions are planned. A three‐part clinimetric program will provide testing of reliability, validity, and responsiveness to interventions. Although the MDS‐UPDRS will not be published until it has successfully passed clinimetric testing, explanation of the process, key changes, and clinimetric programs allow clinicians and researchers to understand and participate in the revision process.

Depression rating scales in Parkinson's disease: critique and recommendations.

Depression is a common comorbid condition in Parkinsons disease (PD) and a major contributor to poor quality of life and disability. However, depression can be difficult to assess in patients with PD due to overlapping symptoms and difficulties in the assessment of depression in cognitively impaired patients. As several rating scales have been used to assess depression in PD (dPD), the Movement Disorder Society commissioned a task force to assess their clinimetric properties and make clinical recommendations regarding their use. A systematic literature review was conducted to explore the use of depression scales in PD and determine which scales should be selected for this review. The scales reviewed were the Beck Depression Inventory (BDI), Hamilton Depression Scale (Ham‐D), Hospital Anxiety and Depression Scale (HADS), Zung Self‐Rating Depression Scale (SDS), Geriatric Depression Scale (GDS), Montgomery‐Asberg Depression Rating Scale (MADRS), Unified Parkinsons Disease Rating Scale (UPDRS) Part I, Cornell Scale for the Assessment of Depression in Dementia (CSDD), and the Center for Epidemiologic Studies Depression Scale (CES‐D). Seven clinical researchers with clinical and research experience in the assessment of dPD were assigned to review the scales using a structured format. The most appropriate scale is dependent on the clinical or research goal. However, observer‐rated scales are preferred if the study or clinical situation permits. For screening purposes, the HAM‐D, BDI, HADS, MADRS, and GDS are valid in dPD. The CES‐D and CSDD are alternative instruments that need validation in dPD. For measurement of severity of depressive symptoms, the Ham‐D, MADRS, BDI, and SDS scales are recommended. Further studies are needed to validate the CSDD, which could be particularly useful for the assessment of severity of dPD in patients with comorbid dementia. To account for overlapping motor and nonmotor symptoms of depression, adjusted instrument cutoff scores may be needed for dPD, and scales to assess severity of motor symptoms (e.g., UPDRS) should also be included to help adjust for confounding factors. The HADS and the GDS include limited motor symptom assessment and may, therefore, be most useful in rating depression severity across a range of PD severity; however, these scales appear insensitive in severe depression. The complex and time‐consuming task of developing a new scale to measure depression specifically for patients with PD is currently not warranted.

White matter changes in mild cognitive impairment and AD: A diffusion tensor imaging study.

Diffusion tensor imaging (DTI) can detect, in vivo, the directionality of molecular diffusion and estimate the microstructural integrity of white matter (WM) tracts. In this study, we examined WM changes in patients with Alzheimers disease (AD) and in subjects with amnestic mild cognitive impairment (MCI) who are at greater risk for developing AD. A DTI index of WM integrity, fractional anisotropy (FA), was calculated in 14 patients with probable mild AD, 14 participants with MCI and 21 elderly healthy controls (NC). Voxel-by-voxel comparisons showed significant regional reductions of FA in participants with MCI and AD compared to controls in multiple posterior white matter regions. Moreover, there was substantial overlap of locations of regional decrease in FA in the MCI and AD groups. These data demonstrate that white matter changes occur in MCI, prior to the development of dementia.

Risk factors for nursing home placement in advanced Parkinson's disease.

We evaluated the risk factors for nursing home placement of patients with Parkinsons disease (PD) by matching 11 PD patients permanently admitted to nursing homes with two control PD patients remaining at home. Risk factors assessed were motor severity, presence of hallucinations/delusions, and presence of memory problems. The only statistically significant risk factor was the presence of hallucinations/delusions. Motor severity and the presence of memory problems did not have an impact on nursing home placement. There was no risk factor synergy for hallucinations, motor disability, and mental impairment. Since all patients in this series who entered nursing homes remained there permanently, these data suggest that vigorous efforts to control hallucinations may be warranted to prevent nursing home placement.

Loss and atrophy of layer II entorhinal cortex neurons in elderly people with mild cognitive impairment.

Layer II of the entorhinal cortex contains the cells of origin for the perforant path, plays a critical role in memory processing, and consistently degenerates in end‐stage Alzheimers disease. The extent to which neuron loss in layer II of entorhinal cortex is related to mild cognitive impairment without dementia has not been extensively investigated. We analyzed 29 participants who came to autopsy from our ongoing longitudinal study of aging and dementia composed of religious clergy (Religious Orders Study). All individuals underwent detailed clinical evaluation within 12 months of death and were categorized as having no cognitive impairment (n = 8), mild cognitive impairment (n = 10), or mild or moderate Alzheimers disease (n = 11). Sections through the entorhinal cortex were immunoreacted with an antibody directed against a neuron‐specific nuclear protein (NeuN). Stereological counts of NeuN‐immunoreactive stellate cells, their volume, and the volume of layer II entorhinal cortex were estimated. Cases exhibiting no cognitive impairment averaged 639,625 ± 184,600 layer II stellate neurons in the right entorhinal cortex. Individuals with mild cognitive impairment (63.5%; p < 0.0003) and mild or moderate Alzheimers disease (46.06%; p < 0.0017) displayed significant losses of layer II entorhinal cortex neurons relative to those with no cognitive impairment but not relative to each other (p > 0.33). There was also significant atrophy of layer II entorhinal cortex neurons in individuals with mild cognitive impairment (24.1%) and Alzheimers disease (25.1%). The volume of layer II was also reduced in individuals with mild cognitive impairment (26.5%), with a further reduction in those with Alzheimers disease (46.4%). The loss and atrophy of layer II entorhinal cortex neurons significantly correlated with performance on clinical tests of declarative memory. Atrophy of layer II entorhinal cortex and the neurons within this layer significantly correlated with performance on the Mini Mental Status Examination. These data indicate that atrophy and loss of layer II entorhinal cortex neurons occur in elderly subjects with mild cognitive impairment prior to the onset of dementia and suggests that these changes are not exacerbated in early Alzheimers disease. Ann Neurol 2001;49:202–213

Sleep-related violence, injury, and REM sleep behavior disorder in Parkinson's disease

Objective: To determine the occurrence of REM sleep behavior disorder (RBD) and sleep-related injury (SRI) in an outpatient PD practice. Background: RBD is a frequent cause of SRI in older individuals. Although RBD is seen in PD, the association of SRI and RBD in PD has not been previously assessed. Design/Methods: Consecutive patients with PD and their caregivers were interviewed using a structured questionnaire assessing the presence of RBD and SRI. Patients fulfilling the International Classification of Sleep Disorders (ICSD) criteria for RBD were compared with non-RBD patients. In a separate analysis, patients with a prior SRI were compared to those without. Results: Of the 61 patient/caregiver pairs, 15% (7 men and 2 women) met the clinical criteria for RBD. There were more episodes of SRI in the RBD group, with 33% causing injury to themselves or to their caregivers compared with 6% of the non-RBD group (χ2 = 13, p = 0.005). In the second analysis, 15% (all men) patient/caregiver pairs reported SRI. Of these, 66% of the patients had behaviors resembling those seen in RBD, and 33% had recalled dream content. There is a significant association between SRI and RBD for dream-enacting sleep behaviors (Fishers exact test, p = 0.0001). Conclusion: PD patients with SRI frequently have behavioral features of RBD. If RBD underlies most SRI, treatment with appropriate pharmacologic agents, such as clonazepam, may prevent future occurrences of SRI.

Mortality and hallucinations in nursing home patients with advanced Parkinson's disease

Article abstract-We monitored 11 patients with advanced Parkinsons disease (PD) who entered nursing homes over a 5-year period and assessed chronicity of nursing home care, mortality, and hallucinatory status. Two years after the original studys close, none of these patients had ever been discharged from the nursing homes and all were dead. The mortality rate among the nursing home patients was significantly greater than that in 22 community-dwelling subjects with PD who were matched for age, gender, and disease duration. Hallucinatory status was generally stable; 82% of patients had the same hallucinatory status (presence or absence) at the two assessments. Four subjects from the original community-dwelling control group entered nursing homes during the follow-up period. Whereas motor and intellectual impairment scores were similar between these patients and the remaining 18 in the community, the presence of hallucinations was significantly greater among patients transferred to nursing homes. The study demonstrates the permanency of nursing home placement in advanced PD and the high mortality associated with such placement. It also documents the chronicity of hallucinatory behavior in these patients with advanced PD and reinforces our previously reported observations on the relationship between hallucinations and placement in chronic-care facilities. NEUROLOGY 1995;45: 669-671