Mild Cognitive Impairment In Parkinson's Disease Research Articles

Diagnostic and screening power of neuropsychological testing in detecting mild cognitive impairment in Parkinson’s disease

Prevalence of mild cognitive impairment (MCI) in Parkinson's disease (PD) is variable likely due to methodological differences in classification criteria and lack of consensus about neuropsychological tests used for cognitive profiling. The main objective of our study was to identify the most suitable neuropsychological tests and determine their screening and diagnostic cutoff scores for PD-MCI. A series of 104 consecutive PD patients performed an extensive neuropsychological evaluation. Individual test values were converted into Z-scores using relative published normative data. According to published criteria, PD patients were categorized as PD-CNT (PD without cognitive impairment), PD-MCI (patients performing -1.5 SDs below the mean score in at least one cognitive domain), and PDD. We used receiver operating characteristic (ROC) curves and K-means clustering analyses to calculate the best discriminating power of each neuropsychological tests in detecting PD-MCI. PD patients were categorized as follows: 55 PD-CNT (53 %), 34 PD-MCI (33 %), and 15 PDD (14 %). PD-MCI had lower education, longer disease duration and greater frequency of hallucinations than PD-CNT. We found that only the Trail Making test, Rey-Osterrieth Complex Figure Test (ROCF) copy, Frontal Assessment Battery (FAB), Digit Span Backward, and Rey's word auditory verbal learning test (RVLT) immediate recall reached significant screening and diagnostic validity in predicting PD-MCI (AUC 0.705-0.795) with cutoff scores calculated by ROC analyses lying within normal range for normative data. Specific neuropsychological tests covering verbal memory, attention/set-shifting, and visual-spatial deficits are the best predictors of MCI in PD if valid cutoff scores are used. These results have consequences for cognitive diagnosis and potentially in establishing the rate of PD cognitive decline.

Pattern of Regional Cortical Thinning Associated with Cognitive Deterioration in Parkinson’s Disease

BackgroundDementia is a frequent and devastating complication in Parkinson’s disease (PD). There is an intensive search for biomarkers that may predict the progression from normal cognition (PD-NC) to dementia (PDD) in PD. Mild cognitive impairment in PD (PD-MCI) seems to represent a transitional state between PD-NC and PDD. Few studies have explored the structural changes that differentiate PD-NC from PD-MCI and PDD patients.Objectives and MethodsWe aimed to analyze changes in cortical thickness on 3.0T Magnetic Resonance Imaging (MRI) across stages of cognitive decline in a prospective sample of PD-NC (n = 26), PD-MCI (n = 26) and PDD (n = 20) patients, compared to a group of healthy subjects (HC) (n = 18). Cortical thickness measurements were made using the automatic software Freesurfer.ResultsIn a sample of 72 PD patients, a pattern of linear and progressive cortical thinning was observed between cognitive groups in cortical areas functionally specialized in declarative memory (entorhinal cortex, anterior temporal pole), semantic knowledge (parahippocampus, fusiform gyrus), and visuoperceptive integration (banks of the superior temporal sulcus, lingual gyrus, cuneus and precuneus). Positive correlation was observed between confrontation naming and thinning in the fusiform gyrus, parahippocampal gyrus and anterior temporal pole; clock copy with thinning of the precuneus, parahippocampal and lingual gyrus; and delayed memory with thinning of the bilateral anteromedial temporal cortex.ConclusionsThe pattern of regional decreased cortical thickness that relates to cognitive deterioration is present in PD-MCI patients, involving areas that play a central role in the storage of prior experiences, integration of external perceptions, and semantic processing.

Trends and Issues in Characterizing Early Cognitive Changes in Parkinson’s Disease

In this review, we first discuss trends and issues in measuring cognitive changes in PD, including recent efforts to define the diagnostic classification of "PD Mild Cognitive Impairment" (PD-MCI). After reviewing some limitations associated with this diagnosis, we discuss how measures derived from the neurocognitive sciences offer better precision in detecting early cognitive changes in PD. To support this idea, we highlight 2 influential lines of current investigation that are unveiling novel insights about specific cognitive processes that are vulnerable early in PD and of critical importance to clinicians involved in treating PD: action control and reward learning and decision making. We conclude by highlighting some extant issues and unresolved questions for future investigations.

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

Mild cognitive impairment is increasingly recognized as a construct in Parkinson's 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.

S5‐02‐03: Parkinson's disease‐mild cognitive impairment (PD‐MCI) and Parkinson's disease Dementia (PDD)

S5‐02‐03: Parkinson's disease‐mild cognitive impairment (PD‐MCI) and Parkinson's disease Dementia (PDD)

Clinical Validity of the Mattis Dementia Rating Scale-2 in Parkinson Disease With MCI and Dementia

The utility of the Mattis Dementia Rating Scale 2 (MDRS-2) in screening for dementia in Parkinson disease (PD) is well documented. However, little is known about its sensitivity to mild cognitive impairment in PD (PD-MCI). This study sought to document the validity of the MDRS-2 for diagnoses of PD-MCI and dementia in PD (PDD). Twenty-two healthy controls (HCs), 22 PD-MCI, and 16 PDD were compared on each MDRS-2 subscales and MDRS-2 total standard scores. Patients with PDD performed significantly worse than the other groups (all Ps < .05) on the MDRS-2 total and on all subscales, except attention. PD-MCI had significant lower scores than HCs on the MDRS-2 total and on initiation/perseveration and memory subscales. The optimal cutoff score for PD-MCI diagnosis was ≤ 140/144 and ≤ 132/144 for PDD. These findings suggest that MDRS-2 is a useful tool to identify dementia but that there might be a ceiling effect in the MDRS-2 cutoff score to diagnose MCI in PD.

1154 The utility of the Addenbrooke's Cognitive Examination-Revised (ACE-R) in Parkinson's disease

IntroductionCognitive impairment is common in Parkinson's disease (PD), even in the early stages, and appropriate screening tools which are suitable for use in the general neurology clinic are needed.MethodsWe investigated...

Diagnostic criteria for mild cognitive impairment in Parkinson's disease: Movement Disorder Society Task Force guidelines

Mild cognitive impairment is common in nondemented Parkinson's 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.

Cognitive Impairment and Dementia in Parkinson’s Disease: Clinical Features, Diagnosis, and Management

Parkinson’s disease (PD) is a common, disabling, neurodegenerative disorder. In addition to classical motor symptoms, non-motor features are now widely accepted as part of the clinical picture, and cognitive decline is a very important aspect of the disease, as it brings an additional significant burden for the patient and caregivers. The diagnosis of cognitive decline in PD, namely mild cognitive impairment (MCI) and dementia, can be extremely challenging, remaining largely based on clinical and cognitive assessments. Diagnostic criteria and methods for PD dementia and MCI have been recently issued by expert work groups. This manuscript has synthesized relevant data in order to obtain a pragmatic and updated review regarding cognitive decline in PD, from milder stages to dementia. This text will summarize clinical features, diagnostic methodology, and therapeutic issues of clinical decline in PD. Relevant clinical genetic issues, including recent advances, will also be approached.

Parkinson’s Disease and Dementia: A Longitudinal Study (DEMPARK)

Background: Parkinson’s disease (PD) is a progressive neurodegenerative motor disorder. However, non-motor complications frequently alter the course of the disease. A particularly disabling non-motor symptom is dementia. Methods/Design: The study is designed as a multicentre prospective, observational cohort study of about 700 PD patients aged 45–80 years with or without dementia and PD-mild cognitive impairment (MCI). The patients will be recruited in eight specialized movement disorder clinics and will be followed for 36 months. Information about the patients’ functional status will be assessed at baseline and 6-/12- month intervals. In addition, 120 patients with dementia with Lewy bodies (DLB) will be included. Well-established standardized questionnaires/tests will be applied for detailed neuropsychological assessment. In addition, patients will be asked to participate in modules including volumetric MRI, genetic parameters, and neuropsychology to detect risk factors, early diagnostic biomarkers and predictors for dementia in PD. Results: The study included 604 PD patients by March 2011; 56.3% were classified as having PD alone, with 30.6% of patients suffering from PD-MCI and 13.1% from PD with dementia. The mean age of the cohort was 68.6 ± 7.9 years, with a mean disease duration of 6.8 ± 5.4 years. There was a preponderance of patients in the earlier Hoehn and Yahr stages. Conclusion: The main aim of the study is to characterize the natural progression of cognitive impairment in PD and to identify factors which contribute to the evolution and/or progression of the cognitive impairment. To accomplish this aim we established a large cohort of PD patients without cognitive dysfunction, PD patients with MCI, and PD patients with dementia, to characterize these patients in a standardized manner, using imaging (serial structural MRI), genetic and proteomic methods in order to improve our understanding of the course of the PD process and the development of cognitive dysfunction and dementia in this disease. The inclusion of the DLB patients will start in the second quarter of 2011 in the BMBF-funded follow-up project LANDSCAPE.

Analysis of the Substantia Innominata Volume in Patients with Parkinson’s Disease with Dementia, Dementia with Lewy Bodies, and Alzheimer’s Disease

Background and PurposeThe substantia innominata (SI) contains the nucleus basalis of Meynert, which is the major source of cholinergic input to the cerebral cortex. We hypothesized that degeneration of the SI and its relationship to general cognitive performance differs in amyloidopathy and synucleinopathy.MethodsWe used magnetic resonance imaging (MRI)-based volumetric analysis to evaluate the SI volume in patients with amnestic mild cognitive impairment (aMCI), Alzheimer’s disease (AD), Parkinson’s disease-mild cognitive impairment (PD-MCI), PD with dementia (PDD), dementia with Lewy bodies (DLB), and healthy elderly controls. The correlation between SI volume and general cognitive performance, measured using the Korean version of the Mini-Mental State Examination (K-MMSE), was examined.ResultsCompared to control subjects, the mean normalized SI volume was significantly decreased in all of the other groups. The normalized SI volume did not differ between the subjects with PDD and DLB, whereas it was significantly smaller in subjects with PDD (p = 0.029) and DLB (p = 0.011) compared with AD. In subjects with PD-related cognitive impairment (PD-MCI, PDD, or DLB), there was a significant positive correlation between the SI volume and K-MMSE score (r = 0.366, p < 0.001), whereas no correlation was seen in subjects with AD-related cognitive impairment (aMCI or AD).ConclusionsOur data suggest that the SI loss is greater in synucleinopathy-related dementia (PDD or DLB) than in AD and that the contribution of the SI to cognitive performance is greater in synucleinopathy than in amyloidopathy.

Comment: should we diagnose MCI in Parkinson disease?

Both Rektorova and Martinez-Horta, and Kulisevsky agreethat Parkinson disease (PD) patients have frequent cogni-tive impairment already at disease onset, which progressesat a varying rate, terminating in dementia in a substantialnumber of patients. Cognitive deterioration in PD followsan indolent course, like that seen in other neurodegenera-tive diseases, and it is an arbitrary decision to term anysection of this process as mild cognitive impairment (MCI),or by any other name. It will be difficult to justify a‘‘starting point’’ of MCI (since deterioration preceded iteven if not fulfilling criteria), and even the conversion todementia is more complicated to define than in Alzheimerdisease (AD), since activities of daily living are impaired inPD by the motor disability, as well as by apathy, depres-sion, etc. which precludes a clear-cut determination as itapplies, for example, to AD.The term MCI has been coined to denote the prede-mentia cognitive impairment stage of AD and has attractedobjections (Ash and Korczyn 2011). Borrowing it to otherdisorders should not be automatic. Several difficulties arestressed in both papers. In addition, it must be recalled thatmany of the PD patients have a unique premorbid per-sonality, they frequently have depression, apathy andsomnolence, are treated by drugs and of course have motorimpairment—each of which could interfere with the exe-cution and interpretation of neuropsychological tests.The common definition of MCI depends on complaintsby the patient (or a close informant). This is particularlytrue for memory impairment, and it is critical to employthis parameter since a deterioration from a previous func-tional level is implied and there are usually no premorbidscores of cognitive testing in AD. However, accepting thatin PD the first cognitive manifestation may be executivedysfunction, what should be the complaints? Clearly, in PDpatients these cannot be just slowness! At present, thisissue has not been addressed.Both Rektorova and Martinez-Horta, and Kulisevskyemphasize the variability of cognitive deterioration. Atpresent, there are few data on factors influencing the rate ofdecline. One of the important factors may be comorbidities,such as co-existent AD or vascular changes (Korczyn2002). These, of course, will complicate further anyinterpretation of cognitive testing.Another very important issue is why diagnose clinicallyinconspicuous or very mild cognitive impairment in PD?In AD, the reason given is that disease modifying therapiesare being developed which should be used early in thecourse of the disease. Since no such therapies are beingdeveloped against the cognitive deterioration in PD, thebenefits from diagnosing an incipient dementia state are notclear. PD patients know that they face deterioration, par-ticularly motor decline. They will not benefit from beingtold that they have been identified as being more likelythan other PD patients to develop dementia as well.References

Mild cognitive impairment exists in Parkinson’s disease

Cognitive impairment exists in Parkinson's disease (PD) as a transitional state between cognitively intact and demented PD patients. It seems to be a risk factor for the development of dementia in PD, but the precise criteria and unfavorable cognitive profile of mild cognitive impairment in PD (MCI-PD) have not yet been established. The concept may turn to be different from that in Alzheimer's disease since we search for those already diagnosed PD patients who are at risk of developing dementia. In addition, clinical variables specific for PD also play role. Importantly, MCI possesses a metabolic basis in PD. Various biomarkers particularly including neuropsychological testing and the brain imaging hold promise in identification of MCI-PD patients with unfavorable prognoses. Well-designed longitudinal studies in MCI-PD cohorts are needed to assess the sensitivity and specificity of the PD-MCI designation as far as dementia development is concerned.

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.

The pattern of cortical atrophy in patients with Parkinson's disease according to cognitive status

Cognitive dysfunction is common in Parkinson's disease (PD), and along with PD with dementia (PDD), the concept of mild cognitive impairment in PD (PD-MCI) has been introduced. To identify structural candidates according to cognitive status in PD, we compared gray matter (GM) density across PD-intact cognition (PD-IC, n = 23), PD-MCI (n = 27), and PDD (n = 18) using voxel-based morphometry. The demographic data among PD subjects were similar, however, general cognition and disease duration were more severe in PD-MCI and PDD than in PD-IC. Compared with controls, GM density was significantly decreased in the left occipital area in PD-IC; the bilateral temporal, left prefrontal and insular, and right occipital areas in PD-MCI; and in widespread brain areas in PDD. Compared with PD-IC, patients with PD-MCI had significantly decreased GM density in the right middle frontal area, and those with PDD had decreased GM density in the right parietal, middle frontal, insular, and lentiform areas. GM density in patients with PDD was significantly decreased in the bilateral middle temporal, right inferior temporal, and left middle and superior prefrontal areas. PDD patients with shorter disease duration before dementia (<5 year) showed greater GM atrophy in the posterior cingulate area than did those with longer disease duration (≥5 year). These data suggest that cortical atrophy in PD exhibits a greater extent with increasing levels of cognitive impairment, and different anatomical substrates would correspond to each cognitive status.

Volumetric analysis of the substantia innominata in patients with Parkinson's disease according to cognitive status

The cholinergic system arising from the substantia innominata (SI) of the basal forebrain has an important role in the cognitive functions of Parkinson's disease (PD). We performed magnetic resonance imaging based volumetric analysis to evaluate the SI volume in patients with PD-intact cognition (PD-IC), PD-mild cognitive impairment (PD-MCI), and PD dementia (PDD). The mean normalized SI volume was significantly decreased in patients with PD-IC (1.54 ± 0.12, p < 0.001), PD-MCI (1.49 ± 0.12, p < 0.001), and PDD (1.39 ± 0.12, p < 0.001) compared with that of control subjects (1.68 ± 0.11). The normalized SI volume did not differ between patients with PD-IC and PD-MCI; however, the normalized SI volume was significantly decreased in patients with PDD compared with that in those with PD-IC (p < 0.001) or PD-MCI (p = 0.016). The normalized SI volume was significantly correlated with general cognitive status (r = 0.51, p < 0.001) as well as with performance in each cognitive subdomain, with a particularly significant independent association with attention (β = 0.33, p = 0.003) and object naming (β = 0.26, p = 0.017). The present study demonstrated that the SI volume in PD differs depending on cognitive status and is significantly correlated with cognitive performance.

Executive functions deficit in Parkinson's disease with amnestic mild cognitive impairment.

Recent studies suggest that onset of dementia in Parkinson's disease (PD) is preceded by a phase known as mild cognitive impairment (MCI). Different clinical subtypes of MCI in PD were found. The objective of this study was to investigate whether patients with PD diagnosed with amnestic MCI (aPD-MCI) have also subtle deficits in other cognitive domains and especially in attention/executive functions and, therefore to clarify whether all subcomponents of executive control are equally affected in aPD-MCI. We investigated 23 patients with aPD-MCI (modified Petersen's criteria) and 25 normal controls. Relative to controls, the aPD-MCI group showed significant deficits with reference to tasks that encompass various aspects of attention/executive functions, including Trail Making Test, Stroop test, Modified Card Sorting Test, and digit span backward, as well as phonemic and semantic verbal fluency. This suggests that executive dysfunction is consistently presented in PD with MCI, even in ''amnestic'' PD-MCI due to cortical-subcortical dysfunction.

The montreal cognitive assessment as a screening tool for cognitive impairment in Parkinson's disease

Cognitive impairment is common in Parkinson's disease (PD) and can occur early in the disease course. No effective screening test exists for detection of early or mild cognitive impairment in PD. We examined the Montreal Cognitive Assessment (MoCA) as a screening tool for cognitive dysfunction in PD. The test-retest intraclass correlation coefficient was 0.79 and the interrater intraclass correlation coefficient was 0.81. The correlation coefficient between the MoCA and a neuropsychologic battery was 0.72. The MoCA is reliable and valid in the PD population and warrants further study as a screening tool for cognitive dysfunction.

Problem solving therapy for the treatment of depression for a patient with Parkinson's disease and mild cognitive impairment: a case study

The present investigation reports on the use of problem solving therapy (PST) to treat depression in an 83-year-old woman with Parkinson's disease (PD) and concurrent mild cognitive impairment (MCI). A neuropsychological evaluation was conducted prior to the intervention and the patient demonstrated mild deficits of executive functioning and memory. The PST treatment consisted of 12 one-hour sessions that occurred weekly. Depressive symptoms were evaluated using the Hamilton Depression Rating scale and the Montgomery-Asberg Depression rating scale. At a post-treatment assessment (week 12), clinician assessment indicated that the client no longer met criteria for MDD. Weekly depression severity ratings showed significant reduction in severity of depressive symptoms over 12 weeks. Results at 1-month and 6-month follow-up demonstrated that the therapeutic gains were not only maintained, but that the client continued to improve. These results suggest that PST may be an effective treatment for the treatment of depression for individuals with a PD and concurrent MCI.

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.