Jennifer G. Goldman

Clinical diagnostic criteria for dementia associated with Parkinson's disease

Dementia has been increasingly more recognized to be a common feature in patients with Parkinsons disease (PD), especially in old age. Specific criteria for the clinical diagnosis of dementia associated with PD (PD‐D), however, have been lacking. A Task Force, organized by the Movement Disorder Study, was charged with the development of clinical diagnostic criteria for PD‐D. The Task Force members were assigned to sub‐committees and performed a systematic review of the literature, based on pre‐defined selection criteria, in order to identify the epidemiological, clinical, auxillary, and pathological features of PD‐D. Clinical diagnostic criteria were then developed based on these findings and group consensus. The incidence of dementia in PD is increased up to six times, point‐prevelance is close to 30%, older age and akinetic‐rigid form are associated with higher risk. PD‐D is characterized by impairment in attention, memory, executive and visuo‐spatial functions, behavioral symptoms such as affective changes, hallucinations, and apathy are frequent. There are no specific ancillary investigations for the diagnosis; the main pathological correlate is Lewy body‐type degeneration in cerebral cortex and limbic structures. Based on the characteristic features associated with this condition, clinical diagnostic criteria for probable and possible PD‐D are proposed.

Diagnostic Criteria for Mild Cognitive Impairment in Parkinson’s Disease: Movement Disorder Society Task Force Guidelines

Mild cognitive impairment is common in nondemented Parkinsons disease (PD) patients and may be a harbinger of dementia. In view of its importance, the Movement Disorder Society commissioned a task force to delineate diagnostic criteria for mild cognitive impairment in PD. The proposed diagnostic criteria are based on a literature review and expert consensus. This article provides guidelines to characterize the clinical syndrome and methods for its diagnosis. The criteria will require validation, and possibly refinement, as additional research improves our understanding of the epidemiology, presentation, neurobiology, assessment, and long‐term course of this clinical syndrome. These diagnostic criteria will support future research efforts to identify at the earliest stage those PD patients at increased risk of progressive cognitive decline and dementia who may benefit from clinical interventions at a predementia stage.

Diagnosis and management of dementia with Lewy bodies Fourth consensus report of the DLB Consortium

The Dementia with Lewy Bodies (DLB) Consortium has refined its recommendations about the clinical and pathologic diagnosis of DLB, updating the previous report, which has been in widespread use for the last decade. The revised DLB consensus criteria now distinguish clearly between clinical features and diagnostic biomarkers, and give guidance about optimal methods to establish and interpret these. Substantial new information has been incorporated about previously reported aspects of DLB, with increased diagnostic weighting given to REM sleep behavior disorder and 123iodine-metaiodobenzylguanidine (MIBG) myocardial scintigraphy. The diagnostic role of other neuroimaging, electrophysiologic, and laboratory investigations is also described. Minor modifications to pathologic methods and criteria are recommended to take account of Alzheimer disease neuropathologic change, to add previously omitted Lewy-related pathology categories, and to include assessments for substantia nigra neuronal loss. Recommendations about clinical management are largely based upon expert opinion since randomized controlled trials in DLB are few. Substantial progress has been made since the previous report in the detection and recognition of DLB as a common and important clinical disorder. During that period it has been incorporated into DSM-5, as major neurocognitive disorder with Lewy bodies. There remains a pressing need to understand the underlying neurobiology and pathophysiology of DLB, to develop and deliver clinical trials with both symptomatic and disease-modifying agents, and to help patients and carers worldwide to inform themselves about the disease, its prognosis, best available treatments, ongoing research, and how to get adequate support.

MDS Task Force on Mild Cognitive Impairment in Parkinson’s disease: Critical Review of PD-MCI

There is controversy regarding the definition and characteristics of mild cognitive impairment in Parkinsons disease. The Movement Disorder Society commissioned a Task Force to critically evaluate the literature and determine the frequency and characteristics of Parkinsons disease–mild cognitive impairment and its association with dementia. A comprehensive PubMed literature review was conducted using systematic inclusion and exclusion criteria. A mean of 26.7% (range, 18.9%–38.2%) of nondemented patients with Parkinsons disease have mild cognitive impairment. The frequency of Parkinsons disease–mild cognitive impairment increases with age, disease duration, and disease severity. Impairments occur in a range of cognitive domains, but single domain impairment is more common than multiple domain impairment, and within single domain impairment, nonamnestic is more common than amnestic impairment. A high proportion of patients with Parkinsons disease–mild cognitive impairment progress to dementia in a relatively short period of time. The primary conclusions of the Task Force are that: (1) Parkinsons disease–mild cognitive impairment is common, (2) there is significant heterogeneity within Parkinsons disease–mild cognitive impairment in the number and types of cognitive domain impairments, (3) Parkinsons disease–mild cognitive impairment appears to place patients at risk of progressing to dementia, and (4) formal diagnostic criteria for Parkinsons disease–mild cognitive impairment are needed.

Premotor and nonmotor features of Parkinson's disease.

PURPOSE OF REVIEW This review highlights recent advances in premotor and nonmotor features in Parkinsons disease, focusing on these issues in the context of prodromal and early-stage Parkinsons disease. RECENT FINDINGS Although Parkinsons disease patients experience a wide range of nonmotor symptoms throughout the disease course, studies demonstrate that nonmotor features are not solely a late manifestation. Indeed, disturbances of smell, sleep, mood, and gastrointestinal function may herald Parkinsons disease or related synucleinopathies and precede these neurodegenerative conditions by 5 or more years. In addition, other nonmotor symptoms such as cognitive impairment are now recognized in incident or de-novo Parkinsons disease cohorts. Many of these nonmotor features reflect disturbances in nondopaminergic systems and early involvement of peripheral and central nervous systems, including olfactory, enteric, and brainstem neurons as in Braaks proposed pathological staging of Parkinsons disease. Current research focuses on identifying potential biomarkers that may detect persons at risk for Parkinsons disease and permit early intervention with neuroprotective or disease-modifying therapeutics. SUMMARY Recent studies provide new insights into the frequency, pathophysiology, and importance of nonmotor features in Parkinsons disease as well as the recognition that these nonmotor symptoms occur in premotor, early, and later phases of Parkinsons disease.

A recommended scale for cognitive screening in clinical trials of Parkinson's disease

Cognitive impairment is common in Parkinsons disease (PD). There is a critical need for a brief, standard cognitive screening measure for use in PD trials whose primary focus is not on cognition. The Parkinson Study Group (PSG) Cognitive/Psychiatric Working Group formed a Task Force to make recommendations for a cognitive scale that could screen for dementia and mild cognitive impairment in clinical trials of PD where cognition is not the primary outcome. This Task Force conducted a systematic literature search for cognitive assessments previously used in a PD population. Scales were then evaluated for their appropriateness to screen for cognitive deficits in clinical trials, including brief administration time (<15 minutes), assessment of the major cognitive domains, and potential to detect subtle cognitive impairment in PD. Five scales of global cognition met the predetermined screening criteria and were considered for review. Based on the Task Forces evaluation criteria the Montreal Cognitive Assessment (MoCA), appeared to be the most suitable measure. This Task Force recommends consideration of the MoCA as a minimum cognitive screening measure in clinical trials of PD where cognitive performance is not the primary outcome measure. The MoCA still requires further study of its diagnostic utility in PD populations but appears to be the most appropriate measure among the currently available brief cognitive assessments. Widespread adoption of a single instrument such as the MoCA in clinical trials can improve comparability between research studies on PD.

New NBIA subtype Genetic, clinical, pathologic, and radiographic features of MPAN

Objective: To assess the frequency of mutations in C19orf12 in the greater neurodegeneration with brain iron accumulation (NBIA) population and further characterize the associated phenotype. Methods: Samples from 161 individuals with idiopathic NBIA were screened, and C19orf12 mutations were identified in 23 subjects. Direct examinations were completed on 8 of these individuals, and medical records were reviewed on all 23. Histochemical and immunohistochemical studies were performed on brain tissue from one deceased subject. Results: A variety of mutations were detected in this cohort, in addition to the Eastern European founder mutation described previously. The characteristic clinical features of mitochondrial membrane protein-associated neurodegeneration (MPAN) across all age groups include cognitive decline progressing to dementia, prominent neuropsychiatric abnormalities, and a motor neuronopathy. A distinctive pattern of brain iron accumulation is universal. Neuropathologic studies revealed neuronal loss, widespread iron deposits, and eosinophilic spheroidal structures in the basal ganglia. Lewy neurites were present in the globus pallidus, and Lewy bodies and neurites were widespread in other areas of the corpus striatum and midbrain structures. Conclusions: MPAN is caused by mutations in C19orf12 leading to NBIA and prominent, widespread Lewy body pathology. The clinical phenotype is recognizable and distinctive, and joins pantothenate kinase–associated neurodegeneration and PLA2G6-associated neurodegeneration as one of the major forms of NBIA.

GBA Variants are associated with a distinct pattern of cognitive deficits in Parkinson's disease

Loss‐of‐function mutations in the GBA gene are associated with more severe cognitive impairment in PD, but the nature of these deficits is not well understood and whether common GBA polymorphisms influence cognitive performance in PD is not yet known.

Exercise improves cognition in Parkinson's disease: The PRET-PD randomized, clinical trial.

This article reports on the findings of the effect of two structured exercise interventions on secondary cognitive outcomes that were gathered as part of the Progressive Resistance Exercise Training in Parkinsons disease (PD) randomized, controlled trial.

Clinical differences among mild cognitive impairment subtypes in Parkinson’s disease

Mild cognitive impairment is increasingly recognized as a construct in Parkinsons disease (PD) and occurs in about 25% of nondemented PD patients. Although executive dysfunction is the most frequent type of cognitive deficit in PD, the cognitive phenotype of PD mild cognitive impairment (PD‐MCI) is broad. PD‐MCI subtypes are represented by amnestic and nonamnestic domain impairment as well as single‐ and multiple‐domain impairment. However, it is unclear whether patients with different PD‐MCI subtypes also differ in other clinical characteristics in addition to cognitive profile. We studied 128 PD‐MCI subjects at our Movement Disorders center, comparing clinical, motor, and behavioral characteristics across the PD‐MCI subtypes. We found varying proportions of impairment subtypes: nonamnestic single domain, 47.7%; amnestic multiple domain, 24.2%; amnestic single domain, 18.8%; and nonamnestic multiple domain, 9.5%. Attentional/executive functioning and visuospatial abilities were the most frequently impaired domains. PD‐MCI subtypes differed in their motor features, with nonamnestic multiple‐domain PD‐MCI subjects showing particularly pronounced problems with postural instability and gait. Differences among PD‐MCI subtypes in age, PD duration, medication use, mood or behavioral disturbances, and vascular disease were not significant. Thus, in addition to differing cognitive profiles, PD‐MCI subtypes differed in motor phenotype and severity but not in mood, behavioral, or vascular comorbidities. Greater postural instability and gait disturbances in the nonamnestic multiple‐domain subtype emphasize shared nondopaminergic neural substrates of gait and cognition in PD. Furthermore, increased burden of cognitive dysfunction, rather than type of cognitive deficit, may be associated with greater motor impairment in PD‐MCI.