We present a clinimetric assessment of the Movement Disorder Society (MDS)-sponsored revision of the Unified Parkinson's 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 Parkinson's disease from 39 sites. We compared the two scales using correlative techniques and factor analysis. The MDS-UPDRS showed high internal consistency (Cronbach's alpha 5 0.79-0.93 across parts) and correlated with the original UPDRS (q 5 0.96). MDS-UPDRS acrosspart 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.2008 Movement Disorder Society

This article presents the revision process, major innovations, and clinimetric testing program for the Movement

Background Mixed pathologies are common in older persons with dementia. Little is known about mixed pathologies in probable AD and about the spectrum of neuropathology in mild cognitive impairment (MCI). Objective Investigate single and mixed common age-related neuropathologies in persons with probable AD and MCI. Methods The study included 483 autopsied participants from the Religious Orders Study and the Rush Memory and Aging Project with probable AD (NINCDS-ARDA criteria), MCI (amnestic and non-amnestic) or no cognitive impairment. We excluded 41 persons with clinically possible AD and 14 with other dementias. We documented the neuropathology of AD (NIA-Reagan Criteria), macroscopic cerebral infarcts, and neocortical Lewy body (LB) disease. Results Of 179 persons (average age = 86.9) with probable AD, 87.7% had pathologically-confirmed AD and 45.8% had mixed pathologies, most commonly AD with macroscopic infarcts (n= 54), followed by AD with neocortical Lewy body disease (n=19) and both (n=8). Of the 134 persons with MCI, 54.4% had pathologically-diagnosed AD, (58.7% in amnestic; 49.2% in non-amnestic); 19.4% had mixed pathologies (22.7% in amnestic; 15.3% in non-amnestic). Macroscopic infarcts without pathologically-diagnosed AD accounted for 4.5% of probable AD, 13.3% of amnestic and 18.6% of non-amnestic MCI. Pure neocortical LB disease was uncommon in all persons with cognitive impairment (<6%). Microscopic infarcts (without macroscopic infarcts) were common as a mixed pathology, but rarely accounted for a clinical diagnosis of probable AD (n=4) or MCI (n=3). Interpretation Clinically-diagnosed probable AD and MCI, even amnestic MCI, are pathologically heterogeneous disorders with many persons exhibiting mixed pathologies.

The mesial premotor cortex (pre-supplementary motor area and supplementary motor area proper), lateral premotor cortex (dorsal premotor cortex and ventral premotor cortex), and primary sensorimotor cortex (primary motor cortex and primary somatosensory cortex) have been identified as key cortical areas for sensorimotor function. However, the three-dimensional (3-D) anatomic boundaries between these regions remain unclear. In order to clarify the locations and boundaries for these six sensorimotor regions, we surveyed 126 articles describing pre-supplementary motor area, supplementary motor area proper, dorsal premotor cortex, ventral premotor cortex, primary motor cortex, and primary somatosensory cortex. Using strict inclusion criteria, we recorded the reported normalized stereotaxic coordinates (Talairach and Tournoux or MNI) from each experiment. We then computed the probability distributions describing the likelihood of activation, and characterized the shape, extent, and area of each sensorimotor region in 3-D. Additionally, we evaluated the nature of the overlap between the six sensorimotor regions. Using the findings from this meta-analysis, along with suggestions and guidelines of previous researchers, we developed the Human Motor Area Template (HMAT) that can be used for ROI analysis.

BackgroundFew pathologic data are available on cerebral vessel disease, dementia, and cognition. This cross-sectional study examined associations of cerebral atherosclerosis and arteriolosclerosis neuropathology with probable and possible Alzheimer’s disease (AD) dementia and level of cognitive function, in a large group of older persons who came to autopsy.Methods1,143 older women or men (median age-at-death = 88.8 years; 42% with AD dementia) underwent annual clinical evaluations and agreed to brain autopsy at time-of-death, as part of one of two cohort studies of aging. Neuropsychological data proximate-to-death were used to create summary measures of global cognition and cognitive domains. Data across all years were used to determine presence of the clinical syndrome of AD dementia. Systematic neuropathologic evaluations documented severity of cerebral large (atherosclerosis) and small vessel disease (arteriolosclerosis). Using regression analyses adjusted for demographics, gross and micro-infarcts and AD pathology, we examined associations of vessel disease severity with odds of probable and possible AD dementia and level of cognition.FindingsModerate-to-severe atherosclerosis was present in 445 (39%) subjects, and arteriolosclerosis in 401 (35%). The odds of AD dementia was higher with moderate-to-severe atherosclerosis (OR=1.33; 95%CI:1.11–1.58) and arteriolosclerosis (OR=1.20; 95%CI:1.04–1.40). Atherosclerosis was associated with lower scores for global cognition (estimate= −0.10, SE=0.04; p=0.00096) and four cognitive domains (episodic memory, semantic memory, perceptual speed and visuospatial abilities; all p<0.019) but not working memory (p=0.21). Arteriolosclerosis was associated with lower scores for global cognition (estimate= −0.10, SE=0.03; p=0.0015) and four domains (all p<0.046), and a borderline/non-significant association was noted for visuospatial abilities (p=0.052). Findings were unchanged in analyses controlling for APOEε4 and vascular risk factors.InterpretationCerebral atherosclerosis and arteriolosclerosis each contribute to the odds of AD dementia by 20–30% per level increase in severity, and are associated with lower scores in most cognitive domains. Associations remain after taking into account AD and infarct pathologies, and vascular factors. Cerebral vessel pathology may be an under-recognized risk factor for AD dementia.FundingUnited States National Institutes of Health.

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Background The effects of progressive resistance exercise (PRE) on the motor signs of Parkinson’s disease have not been studied in controlled trials. Our aim was to compare 6, 12, 18, and 24 month outcomes of patients with Parkinson’s disease who received PRE to a stretching, balance, and strengthening exercise program. Methods We conducted a randomized controlled trial between September 2007 and July 2011. Pairs of patients, matched by sex and off-medication Unified Parkinson’s Disease Rating Scale, motor subscale (UPDRS-III), were randomly assigned to the interventions with a 1:1 allocation ratio. The PRE group performed a weight lifting program. The Modified Fitness Counts (mFC) group performed a stretching, balance, and strengthening exercise program. Patients exercised two days per week for 24 months at a gym. A personal trainer directed both weekly sessions for the first six months and one weekly session after six months. The primary outcome was the off-medication UPDRS-III score. Patients were followed for 24 months at six-month intervals. Results Of 51 patients, 20 in PRE and 18 in mFC completed the trial. At 24 months, the mean off-medication UPDRS-III score decreased more with PRE than with mFC (mean difference: - 7·3 points; 95% CI: -11·3 to -3·6; P < 0·001). The PRE group had ten adverse events. The mFC group had seven adverse events. Conclusions PRE demonstrated a statistically and clinically significant reduction in UPDRS-III scores compared to mFC and is recommended as a useful adjunct therapy to improve Parkinsonian motor signs.

Background and Purpose-Little is known about the role of microinfarcts in dementia and cognition. We examined microinfarcts and dementia, global cognition, and 5 cognitive systems in community-dwelling older persons. Methods-Four hundred twenty-five subjects enrolled in the Religious Orders Study underwent annual clinical evaluations, including 19 neuropsychological tests and assessment for dementia, and brain autopsy (39% men; mean age at death, 87; Mini-Mental State Examination score, 21). Neuropathologic examination documented the presence, number, and location of chronic microinfarcts on 6-m hematoxylin-eosin-stained sections from cortical and subcortical regions. Multiple regression analyses adjusted for age at death, sex, education, macroscopic infarcts, Alzheimer disease pathology, and Lewy bodies. Results-Microinfarcts were present in 129 of 425 (30%) persons (54 cortical, 80 subcortical, 49 multiple); 58 of 129 (45%) of persons with microinfarcts did not exhibit macroscopic infarcts. Persons with microinfarcts had increased odds of dementia (OR, 1.77; 95% CI, 1.07-2.92), especially those persons with multiple cortical microinfarcts. Microinfarcts were also associated with lower average global cognition (estimate, Ϫ0.287; SE, 0.113; Pϭ0.012), particularly for persons with multiple cortical microinfarcts. Microinfarcts were specifically associated with lower episodic memory (estimate, Ϫ0.279; SE, 0.138; Pϭ0.044), semantic memory (estimate, Ϫ0.391; SE, 0.130; Pϭ0.003), and perceptual speed (estimate, Ϫ0.400; SE, 0.117; PϽ0.001). In addition, single, multiple, and cortical microinfarcts were associated with worse semantic memory and perceptual speed (all PϽ0.028). Neither macroscopic infarcts nor AD pathology modified these associations (all PϾ0.154). Conclusions-Microinfarcts are common, and persons with multiple cortical microinfarcts have higher odds of dementia.Microinfarcts are also associated with lower cognition, specifically perceptual speed and semantic and episodic memory. Key Words: cognition Ⅲ demential Ⅲ microinfarct Ⅲ pathology B rain infarcts are common in older persons and are increasingly recognized with improved medical technology. Although sophisticated neuroimaging is contributing to better identification of small infarcts, 1 microinfarcts are, by definition, not visible to the naked eye and are detected only on histological examination. Microinfarcts have been associated with macroscopic infarcts 2 and commonly coexist with Alzheimer disease (AD) pathology. 3 The role of microinfarcts in the context of mixed pathologies (ie, AD pathology, macroscopic infarcts, and Lewy bodies) commonly found in brains of older persons with dementia is not well-understood.Few clinical-pathological, prospective, community studies examine associations of microinfarcts with other pathologies, cognition, or dementia. Some have found that despite their small size, microinfarcts are associated with dementia or cognition, particularly if multiple and cortical. 4 -8 It is uncertain if microinfarcts affect speci...