Defining mild cognitive impairment in Parkinson's disease

Our purpose was to characterize a state of mild cognitive impairment (MCI) in Parkinson's disease (PD) (PD‐MCI) that would be analogous to the MCI that is posited as a precursor of Alzheimer's disease (AD). We categorized 86 PD subjects in a brain bank population as either cognitively normal (PD‐CogNL), PD‐MCI using criteria that included a 1.5 standard deviation or greater deficit upon neuropsychological testing consistently across at least one cognitive domain without dementia, and PD dementia (PD‐D) using DSM‐IV criteria. Twenty‐one percent of our PD sample met criteria for PD‐MCI, 62% were PD‐CogNL, and 17% had PD‐D. The mean duration of PD and MMSE scores of the PD‐MCI group were intermediate and significantly different from both PD‐CogNL and PD‐D. The cognitive domain most frequently abnormal in PD‐MCI was frontal/executive dysfunction followed by amnestic deficit. Single domain PD‐MCI was more common than PD‐MCI involving multiple domains. We conclude that a stage of clinical cognitive impairment in PD exists between PD‐CogNL and PD‐D, and it may be defined by applying criteria similar to the MCI that is posited as a precursor of AD. Defining PD‐MCI offers an opportunity for further study of cognitive impairment in PD and targets for earlier therapeutic intervention. © 2007 Movement Disorder Society     

Measuring mild cognitive impairment in patients with Parkinson's disease

We examined the frequency of Parkinson disease with mild cognitive impairment (PD‐MCI) and its subtypes and the accuracy of 3 cognitive scales for detecting PD‐MCI using the new criteria for PD‐MCI proposed by the Movement Disorders Society. Nondemented patients with Parkinson's disease completed a clinical visit with the 3 screening tests followed 1 to 3 weeks later by neuropsychological testing. Of 139 patients, 46 met Level 2 Task Force criteria for PD‐MCI when impaired performance was based on comparisons with normative scores. Forty‐two patients (93%) had multi‐domain MCI. At the lowest cutoff levels that provided at least 80% sensitivity, specificity was 44% for the Montreal Cognitive Assessment and 33% for the Scales for Outcomes in Parkinson's Disease‐Cognition. The Mini‐Mental State Examination could not achieve 80% sensitivity at any cutoff score. At the highest cutoff levels that provided specificity of at least 80%, sensitivities were low (≤44%) for all tests. When decline from estimated premorbid levels was considered evidence of cognitive impairment, 110 of 139 patients were classified with PD‐MCI, and 103 (94%) had multi‐domain MCI. We observed dramatic differences in the proportion of patients who had PD‐MCI using the new Level 2 criteria, depending on whether or not decline from premorbid level of intellectual function was considered. Recommendations for methods of operationalizing decline from premorbid levels constitute an unmet need. Among the 3 screening tests examined, none of the instruments provided good combined sensitivity and specificity for PD‐MCI. Other tests recommended by the Task Force Level 1 criteria may represent better choices, and these should be the subject of future research. © 2013 Movement Disorder Society     

Characterizing mild cognitive impairment in Parkinson's disease

There is growing interest in identifying Parkinson's disease (PD) patients with mild cognitive impairment (PD‐MCI), but widely disparate criteria have been used. We assessed 143 PD patients and 50 matched controls on 20 measures across 4 cognitive domains (executive function, attention and working memory, learning and memory, visuoperception). Twenty‐four patients met criteria for dementia (PD‐D); nondementia patients were classified as either with normal cognition or MCI for 12 neuropsychological criteria. We compared the influence of these criteria on the distribution of global cognitive performance in the resulting PD‐MCI groups relative to the control and PD‐D groups. Different criteria produced substantial variation in the proportion of PD‐MCI cases identified. Fourteen percent PD‐MCI was found when using 2 scores in 1 domain at 2 standard deviations (SD) below normative scores, with no controls identified as MCI, through to 89% PD‐MCI with 1 score in 1 domain at 1 SD below normative scores, when 70% of controls were identified as MCI. The balance of cases with impaired cognition but not those with generally intact cognition was better served by using criteria that required 2 specific deficit scores or deficits across 2 domains. As comparisons with external normative data may have greater applicability across centers, we suggest that 2 scores at ?1.5 SD within any single domain (30% PD‐MCI) or 1 score at ?1.5 SD in each of 2 domains (37% PD‐MCI) provide suitable criteria to minimize the inclusion of cognitively well patients. Clinical dementia rating did not improve the relative identification of cognitively impaired and unimpaired nondementia PD patients. © 2011 Movement Disorder Society     

Subtypes of mild cognitive impairment in Parkinson's disease: progression to dementia.

The aim of this study was to establish the rate of progression from mild cognitive impairment (MCI) to dementia in patients with Parkinson's disease (PD). PD patients without dementia were recruited in 1997 from an ongoing prospective epidemiological study. The assessment included neurological and psychiatric examinations, a clinical interview based on the Diagnostic and Statistical Manual of Mental Disorders, Revised Third Edition (DSM-III-R) criteria for dementia, and a battery of neuropsychological tests. PD was diagnosed according to established criteria, dementia was diagnosed according to the DSM-III-R criteria, and subtypes of MCI were classified according to modified Petersen's criteria. Seventy-two nondemented PD patients were included. A total of 34 were cognitively intact, whereas 38 were diagnosed with MCI (amnestic, n = 6; single nonmemory domain, n = 17; multiple domains slightly impaired, n = 15). Fifty-nine patients (82%) completed follow-up examination 4 years later, and 18 (62%) of the patients with MCI and 6 (20%) of the cognitively intact PD patients were demented (P = 0.001). Single domain nonmemory MCI and multiple domains slightly impaired MCI were associated with later development of dementia (P = 0.003; P = 0.04), whereas amnestic MCI subtype was not (P = 0.76). We conclude that patients with PD and MCI had a higher risk of developing dementia than cognitively intact PD patients, suggesting that MCI in PD is an early manifestation of dementia. However, these findings should be interpreted with caution due to the relatively small number of subjects included in this study.     

Biomarkers for dementia and mild cognitive impairment in Parkinson's disease

Cognitive decline is one of the most frequent and disabling nonmotor features of Parkinson's disease. Around 30% of patients with Parkinson's disease experience mild cognitive impairment, a well‐established risk factor for the development of dementia. However, mild cognitive impairment in patients with Parkinson's disease is a heterogeneous entity that involves different types and extents of cognitive deficits. Because it is not currently known which type of mild cognitive impairment confers a higher risk of progression to dementia, it would be useful to define biomarkers that could identify these patients to better study disease progression and possible interventions. In this sense, the identification among patients with Parkinson's disease and mild cognitive impairment of biomarkers associated with dementia would allow the early detection of this process. This review summarizes studies from the past 25 years that have assessed the potential biomarkers of dementia and mild cognitive impairment in Parkinson's disease patients. Despite the potential importance, no biomarker has as yet been validated. However, features such as low levels of epidermal and insulin‐like growth factors or uric acid in plasma/serum and of Aß in CSF, reduction of cerebral cholinergic innervation and metabolism measured by PET mainly in posterior areas, and hippocampal atrophy in MRI might be indicative of distinct deficits with a distinct risk of dementia in subgroups of patients. Longitudinal studies combining the existing techniques and new approaches are needed to identify patients at higher risk of dementia. © 2016 International Parkinson and Movement Disorder Society     

An assessment of Movement Disorder Society Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease

Background and purpose

Cognitive impairment is one of the most disabling non‐motor symptoms of Parkinson's disease. Mild cognitive impairment constitutes a major risk for the development of Parkinson's disease dementia in the course of the disease. A Movement Disorder Society Task Force proposed diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD‐MCI), comprising two operational levels: Level I and Level II. The objective of our study was to test the accuracy of Level I versus Level II diagnostic criteria.

Methods

Eighty‐six consecutive patients with Parkinson's disease were screened and 68 patients without dementia or depression were included in the study. We used the Montreal Cognitive Assessment, Mini‐Mental State Examination and Addenbrooke's Cognitive Evaluation‐R screening tools for Level I and an extensive neuropsychological battery for Level II assessment. We first diagnosed PD‐MCI on the basis of Level II assessment and then calculated sensitivity, specificity and area under the receiver–operator characteristics curve, comparing the performance of the three screening batteries.

Results

None of the three screening batteries proposed for Level I assessment provided satisfactory combined sensitivity and specificity for detecting PD‐MCI, and their performance was similar. Using the Level II criteria, 29 patients (43%) were diagnosed as having PD‐MCI. Lowest cut‐off levels that provided at least 80% sensitivity were 24 for the Montreal Cognitive Assessment, 29 for the Mini‐Mental State Examination and 87 for the Addenbrooke's Cognitive Evaluation‐R. However, specificity levels were below 80% at these cut‐off levels.

Conclusions

We conclude that Level I assessment alone using screening batteries is not sufficiently sensitive/specific to detect PD‐MCI.     

Amnestic mild cognitive impairment in Parkinson's disease: A brain perfusion SPECT study

The purpose of this study was to investigate cortical dysfunction in Parkinson's disease (PD) patients with amnestic deficit (PD‐MCI). Perfusion single photon emission computed tomography was performed in 15 PD‐MCI patients and compared (statistical parametric mapping [SPM2]) with three groups, i.e., healthy subjects (CTR), cognitively intact PD patients (PD), and common amnestic MCI patients (aMCI). Age, depression, and UPDRS‐III scores were considered as confounding variables. PD‐MCI group (P < 0.05, false discovery rate–corrected for multiple comparisons) showed relative hypoperfusion in bilateral posterior parietal lobe and in right occipital lobe in comparison to CTR. As compared to aMCI, MCI‐PD demonstrated hypoperfusion in bilateral posterior parietal and occipital areas, mainly right cuneus and angular gyrus, and left precuneus and middle occipital gyrus. With a less conservative threshold (uncorrected P < 0.01), MCI‐PD showed hypoperfusion in a left parietal region, mainly including precuneus and inferior parietal lobule, and in a right temporal‐parietal‐occipital region, including middle occipital and superior temporal gyri, and cuneus‐precuneus, as compared to PD. aMCI versus PD‐MCI showed hypoperfusion in bilateral medial temporal lobe, anterior cingulate, and left orbitofrontal cortex. PD‐MCI patients with amnestic deficit showed cortical dysfunction in bilateral posterior parietal and occipital lobes, a pattern that can be especially recognized versus both controls and common aMCI patients, and to a lesser extent versus cognitively intact PD. The relevance of this pattern in predicting dementia should be evaluated in longitudinal studies. © 2008 Movement Disorder Society     

Loss of awareness of hyposmia is associated with mild cognitive impairment in Parkinson's disease

BackgroundHyposmia is a common non-motor symptom in Parkinson's disease (PD). However, patients with PD are sometimes unaware of their olfactory dysfunction, resulting in an under-diagnosis of this symptom. To determine whether the loss of awareness of hyposmia results from cognitive impairment in patients with PD, we investigated the relationship between the degree of hyposmia self-awareness and the cognitive status of non-demented PD patients.MethodsThirty-one non-demented patients with PD and 20 healthy controls (HC) were assessed via a self-reported olfactory questionnaire and an odor identification test. PD patients were sub-classified as having mild cognitive impairment (PD-MCI) or as cognitively normal (PD-CN) (according to the current PD-MCI criteria). We compared the degree of hyposmia self-awareness between the PD-MCI and PD-CN groups.ResultsThe PD-MCI group scored the lowest on the odor identification test among all groups, whereas PD-MCI patients tended to rate their olfactory function higher on the self-reported olfactory questionnaire than PD-CN patients. Differences in the scores of subjective and objective olfactory measures between the PD-MCI and PD-CN groups were significant (p = 0.0069).ConclusionsThe loss of awareness of hyposmia is closely associated with mild cognitive impairment (MCI) in PD patients.     

Ventricular enlargement and mild cognitive impairment in early Parkinson's disease

Mild cognitive impairment (MCI) may predict future development of dementia in Parkinson's disease (PD). We aimed to examine the extent of subcortical brain atrophy in patients with early PD with and without MCI compared to normal controls (NC). Participating in a population‐based study were 43 early, drug‐naïve PD patients and 41 NC. Eleven patients were classified with MCI (MCI PD) and 32 patients without (non‐MCI PD). Volumetric segmentation of 3D‐T1 weighted brain MRI was performed using FreeSurfer. Groups were compared applying MANCOVA corrected for total intracranial volume, age, and sex. Results showed that left inferior lateral ventricle and third ventricle volumes were significantly larger in MCI PD than in non‐MCI PD and NC. Fourth ventricular size in MCI PD was significantly different from NC and highly correlated with memory performance in MCI PD patients. This suggests that cognitive dysfunction in early PD may be associated with ventricular enlargement. © 2010 Movement Disorder Society     

Impaired financial abilities in Parkinson's disease patients with mild cognitive impairment and dementia

PurposeFinancial capacity (FC) is an instrumental activity of daily living (IADL) critical to independent functioning and sensitive to cognitive impairment in dementia. Little is known about FC in cognitively impaired patients with Parkinson's disease (PD). The present study investigated FC in PD patients with prodromal and clinical dementia.MethodsParticipants were 20 older controls and 35 PD patients who met consensus criteria for either mild cognitive impairment (PD-MCI, n = 18) or PD dementia (PDD, n = 17). FC was assessed using a standardized performance based measure consisting of 9 domain and two global scores (Financial Capacity Instrument; FCI) (1). FCI domain and global performance scores were compared across groups. Capacity impairment ratings (no impairment, mild/moderate impairment, severe impairment) were calculated for each PD patient's domain and global scores.ResultsRelative to controls, PD-MCI patients were impaired on both FCI global scores and domains of basic monetary skills, financial concepts, and investment decision-making. Relative to both controls and PD-MCI patients, PDD patients were impaired on virtually all FCI variables. With respect to impairment ratings, greater than 50% of PD-MCI patients and greater than 90% of PDD patients were classified as either mild/moderate or severely impaired on the two FCI global scores.ConclusionsImpairment of financial capacity is already present in PD-MCI and is advanced in PDD. Complex cognitively-mediated IADLs such as financial capacity appear to be impaired early in the course of PD dementia.     

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 Parkinson's disease. The Movement Disorder Society commissioned a Task Force to critically evaluate the literature and determine the frequency and characteristics of Parkinson's 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 Parkinson's disease have mild cognitive impairment. The frequency of Parkinson's 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 Parkinson's disease–mild cognitive impairment progress to dementia in a relatively short period of time. The primary conclusions of the Task Force are that: (1) Parkinson's disease–mild cognitive impairment is common, (2) there is significant heterogeneity within Parkinson's disease–mild cognitive impairment in the number and types of cognitive domain impairments, (3) Parkinson's disease–mild cognitive impairment appears to place patients at risk of progressing to dementia, and (4) formal diagnostic criteria for Parkinson's disease–mild cognitive impairment are needed. © 2011 Movement Disorder Society     

Subjective cognitive complaints in patients with Parkinson's disease

Mild cognitive impairment (MCI) is common in Parkinson's disease (PD), affecting almost all patients with PD at some time. It has been shown that patients with PD, who express subjective cognitive complaints, are at a higher risk of eventually developing PD‐MCI. This is corroborated by the Movement Disorders Society's (MDS) diagnostic criteria from 2012 for PD‐MCI, from which it follows that a subjective cognitive complaint must be present in addition to objective cognitive impairment for a patient with PD to receive a diagnosis of PD‐MCI. Nevertheless, there is currently no standardized measurement available for assessing subjective cognitive complaints. Therefore, this review aims to generate an overview of how subjective cognitive complaints are commonly operationalized in the empirical literature as well as whether they are found to be associated with the level of cognitive impairment. The findings revealed that a broad range of measures has been used to obtain subjective cognitive complaints and that there is little consistency between different studies with regard to how they have obtained these complaints, from whom they had obtained them, how many they have obtained, which types of complaints they have obtained and whether they were associated with cognitive impairment. Given the fact that the presence of subjective cognitive complaints is a requirement for setting a diagnosis, there is a need for more methodological consensus with regard to the measurement hereof.     

Defining optimal cutoff scores for cognitive impairment using Movement Disorder Society Task Force criteria for mild cognitive impairment in Parkinson's disease

The recently proposed Movement Disorder Society (MDS) Task Force diagnostic criteria for mild cognitive impairment in Parkinson's disease (PD‐MCI) represent a first step toward a uniform definition of PD‐MCI across multiple clinical and research settings. However, several questions regarding specific criteria remain unanswered, including optimal cutoff scores by which to define impairment on neuropsychological tests. Seventy‐six non‐demented PD patients underwent comprehensive neuropsychological assessment and were classified as PD‐MCI or PD with normal cognition (PD‐NC). The concordance of PD‐MCI diagnosis by MDS Task Force Level II criteria (comprehensive assessment), using a range of standard deviation (SD) cutoff scores, was compared with our consensus diagnosis of PD‐MCI or PD‐NC. Sensitivity, specificity, and positive and negative predictive values were examined for each cutoff score. PD‐MCI subtype classification and distribution of cognitive domains impaired were evaluated. Concordance for PD‐MCI diagnosis was greatest for defining impairment on neuropsychological tests using a 2 SD cutoff score below appropriate norms. This cutoff also provided the best discriminatory properties for separating PD‐MCI from PD‐NC compared with other cutoff scores. With the MDS PD‐MCI criteria, multiple domain impairment was more frequent than single domain impairment, with predominant executive function, memory, and visuospatial function deficits. Application of the MDS Task Force PD‐MCI Level II diagnostic criteria demonstrates good sensitivity and specificity at a 2 SD cutoff score. The predominance of multiple domain impairment in PD‐MCI with the Level II criteria suggests not only influences of testing abnormality requirements, but also the widespread nature of cognitive deficits within PD‐MCI. © 2013 International Parkinson and Movement Disorder Society     

Parkinson's disease‐cognitive rating scale: Psychometrics for mild cognitive impairment

Lack of validated data on cutoff scores for mild cognitive impairment (MCI) and sensitivity to change in predementia stages of Parkinson's disease (PD) limit the utility of instruments measuring global cognition as screening and outcome measures in therapeutic trials. Investigators who were blinded to PD‐Cognitive Rating Scale (PD‐CRS) scores classified a cohort of prospectively recruited, nondemented patients into a PD with normal cognition (PD‐NC) group and a PD with MCI (PD‐MCI) group using Clinical Dementia Rating (CDR) and the Mattis Dementia Rating Scale‐2 (MDRS‐2). The discriminative power of the PD‐CRS for PD‐MCI was examined in a representative sample of 234 patients (145 in the PD‐NC group; 89 in the PD‐MCI group) and in a control group of 98 healthy individuals. Sensitivity to change in the PD‐CRS score (the minimal clinically important difference was examined with the Clinical Global Impression of Change scale and was calculated with a combination of distribution‐based and anchor‐based approaches) was explored in a 6‐month observational multicenter trial involving a subset of 120 patients (PD‐NC, 63; PD‐MCI, 57). Regression analysis demonstrated that PD‐CRS total scores (P < 0.001) and age (P = 0.01) independently differentiated PD‐NC from PD‐MCI. Area under the receiver operating characteristic curve (AUC) analysis (AUC, 0.85; 95% confidence interval, 0.80–0.90) indicated that a score ≤81 of 134 was the optimal cutoff point on the total score for the PD‐CRS (sensitivity, 79%; specificity, 80%; positive predictive value, 59%; negative predictive value, 91%). A range of change from 10 to 13 points on the PD‐CRS total score was indicative of clinically significant change. These findings suggest that the PD‐CRS is a useful tool to identify PD‐MCI and to track cognitive changes in nondemented patients with PD. © 2013 International Parkinson and Movement Disorder Society