Striatal dopamine transporter imaging correlates with depressive symptoms and tower of London task performance in Parkinson's disease

We studied whether the ¹²³I‐FP‐CIT uptake in the striatum correlates with depressive symptoms and cognitive performance in patients with Parkinson's disease (PD). Twenty patients with PD without major depression and/or dementia (mean age 61.7 ± 12.7 years) underwent the ¹²³I‐FP‐CIT SPECT. Depressive symptoms and cognitive performance were assessed in the ON state. The ratios of striatal to occipital binding for the entire striatum, putamina, and putamen to the caudate (put/caud) index were calculated in the basal ganglia. The association between neuropsychiatric measures and dopamine transporter (DAT) availability was calculated; multiple regression analysis was used to assess association with age and disease duration. We found significant correlations between Montgomery and Asberg Depression Rating Scale (MARDS) and Tower of London (TOL) task scores and ¹²³I‐FP‐CIT uptake in various striatal ROIs. Multiple regression analysis confirmed the significant relationship between TOL performance and put/caud ratio (P = 0.001) and to age (P = 0.001), and between MADRS and left striatal (P = 0.005) and putaminal DAT availability (P = 0.003). Our pilot study results demonstrate that imaging with ¹²³I‐FP‐CIT SPECT appears to be sensitive for detecting dopaminergic deficit associated with mild depressive symptoms and specific cognitive dysfunction in patients with PD, yet without a current depressive episode and/or dementia. © 2008 Movement Disorder Society     

The relation between cognition and motor dysfunction in drug‐naive newly diagnosed patients with Parkinson's disease

Recent studies have reported cognitive decline to be common in the early phase of Parkinson's disease. Imaging data connect working memory and executive functioning to the dopamine system. It has also been suggested that bradykinesia is the clinical manifestation most closely related to the nigrostriatal lesion. Exploring the relationship between motor dysfunction and cognition can help us find shared or overlapping systems serving different functions. This relationship has been sparsely investigated in population‐based studies of untreated Parkinson's disease. The aim of the present study was to investigate the association between motor signs and cognitive performance in the early stages of Parkinson's disease before the intake of dopaminergic medication. Patients were identified in a population‐based study of incident cases with idiopathic parkinsonism. Patients with the postural instability and gait disturbances phenotype were compared with patients with the tremor‐dominant phenotype on demographics and cognitive measures. Associations between cognitive and motor scores were investigated, with age, education, and sex controlled for. Bradykinesia was associated with working memory and mental flexibility, whereas axial signs were associated with episodic memory and visuospatial functioning. No significant differences in the neuropsychological variables were found between the postural instability and gait disturbances phenotype and the tremor phenotype. Our results indicate a shared system for slow movement and inflexible thinking that may be controlled by a dopaminergic network different from dopaminergic networks involved in tremor and/or rigidity. The association between axial signs and memory and visuospatial function may point to overlapping systems or pathologies related to these abilities. © 2011 Movement Disorder Society     

Brain atrophy and white matter hyperintensities in early Parkinson's disease

The purpose of this research was to examine the extent of global brain atrophy and white matter hyperintensities (WMH) in early Parkinson's disease (PD) compared to normal controls (NC), to explore the relationship between the MRI variables and cognition in PD. In this multicenter study we included 155 PD patients (age 65.6 ± 9.1 years, disease duration 26.7 ± 19.9 months) and 101 age‐matched NC. On 3D‐T1‐WI, we calculated normalized brain volumes using SIENAX software. WMH volumes were assessed semiautomatically. In PD patients, correlation and regression analyses investigated the association between atrophy and WMH outcomes and global, attention‐executive, visuospatial, and memory cognitive functions. Regression analysis was controlled for age, education, depression score, motor severity, cerebrovascular risk, and sex. No significant MRI variable volume group differences were found. The models did not retain any of the imaging variables as significant predictors of cognitive impairment. There was no evidence of brain atrophy or higher WMH volume in PD compared to NC, and MRI volumetric measurements were not significant predictors of cognitive functions in PD patients. We conclude that global structural brain changes are not a major feature in patients with incident PD. © 2009 Movement Disorder Society     

Volumetric correlates of cognitive functioning in nondemented patients with Parkinson's disease

A challenge in Parkinson's disease (PD) is to identify biomarkers of early cognitive change because functioning in some domains may be more prognostic of dementia. Few studies have investigated whether structural magnetic resonance imaging (MRI) correlates in a regionally specific manner with functioning in different cognitive domains. The aim of this study was to identify neuroanatomical correlates of executive functioning, memory, and visual cognition in PD without dementia. 3T MRI was conducted in 51 PD patients and 39 control participants. Brain volumes were measured in structures comprising the frontostriatal cognitive‐control system, the medial temporal memory system, the ventral object‐based system, and the dorsal spatial‐based system. Measures of executive functioning (Stroop Test; Letter Fluency), memory (California Verbal Learning Test), visuospatial cognition (Judgment of Line Orientation), and visuoconstruction (Pentagon Copy) were correlated with volumes comprising each system. Poorer executive functioning largely correlated with decreased frontostriatal volumes. Poorer memory correlated with decreased volumes in all medial temporal regions, but also with frontostriatal volumes. Poorer visuospatial cognition correlated with decreased volumes in the object‐based system, whereas poorer visuoconstruction correlated with decreased frontal and object‐based system volumes. These relationships were nonsignificant in the control group. This is the first study to demonstrate that subtle changes in multiple cognitive domains in PD without dementia correlate with regional volumes in specific systems implicated in the development of cognitive impairment. The findings suggest that structural MRI holds promise as a marker of early changes in different brain systems, some of which may predict future cognitive deterioration. © 2013 Movement Disorder Society     

The effects of rasagiline on cognitive deficits in Parkinson's disease patients without dementia: A randomized,double‐blind,placebo‐controlled,multicenter study

Cognitive impairment can occur at all stages of Parkinson's disease. Rasagiline is a selective monoamine oxidase type‐B inhibitor that enhances central dopaminergic transmission. Dopamine is thought to be involved in certain cognitive processes such as working memory. We assessed the effects of rasagiline on cognitive deficits in cognitively impaired, nondemented patients with Parkinson's disease. This was a randomized, double‐blind, placebo‐controlled prospective study. Patients with Parkinson's disease receiving stable dopaminergic treatment were assigned to receive rasagiline 1 mg/day or placebo for 3 months. Patients were eligible if they had impairment in 2 of 4 cognitive domains (attention, executive functions, memory, visuospatial functions) in the screening neuropsychological tests, yet did not fulfill criteria for Parkinson's disease dementia. Fifty‐five patients were randomized; 48 patients completed the study. Patients in the rasagiline group showed significant improvement in digit span–backward compared with the placebo group (P = .04), with trends favoring rasagiline in digit span total and digit‐ordering tests. Verbal fluency total score showed a significant difference in favor of rasagiline (P = .038), with trends favoring rasagiline in semantic fluency test and Stroop spontaneous corrections. The composite cognitive domain Z scores revealed a significant difference in favor of rasagiline compared with placebo in the attentional Z score (P < .005). There were no significant differences between the 2 groups in the other cognitive tests or cognitive domain Z scores. The monoamine oxidase type‐B inhibitor rasagiline may exert beneficial effects on certain aspects of attention and executive functions in nondemented patients with Parkinson's disease with cognitive impairment. © 2011 Movement Disorder Society     

DaTSCAN (123I-FP-CIT SPECT) imaging in early versus mid and late onset Parkinson's disease: Longitudinal data from the PPMI study

IntroductionIt has been reported that early onset Parkinson's Disease (PD) patients have a less profound dopaminergic degeneration. The aim of the current study was to determine whether there are longitudinal differences in dopaminergic denervation [signal reduction in 123I-FP-CIT SPECT] in early versus mid and late onset PD.MethodsDaTSCAN (123I-FP-CIT SPECT) imaging was acquired at Parkinson's Progression Markers Initiative (PPMI) imaging centers and sent to the imaging core for calculation of striatal binding ratios. Data from the PPMI database of 58 early de novo PD patients (age ≤ 50 years) were compared to those of 362 mid and late onset PD patients (age > 50 years).ResultsAlthough raw striatal binding ratios were higher in early onset versus mid/late onset PD, especially on the ipsilateral side, such differences were not observed, and were in fact reversed in the contralateral putamen, after age correction. The rate of signal decline was similar between the two groups. Interestingly, based on both raw and age-adjusted data, caudate nucleus and putamen asymmetry (contralateral/ipsilateral ratio) was more pronounced in early onset PD. Striatal asymmetry also significantly correlated with age at onset as a continuous variable.ConclusionEarly onset PD patients exhibited similar rates of decline of dopaminergic denervation compared to mid/late onset PD. These results are not supportive of a more benign disease in this subgroup. The more pronounced asymmetry in early onset PD may however signify a qualitatively different pattern of neurodegeneration compared to mid/late onset PD.     

Dopamine transporter imaging is associated with long‐term outcomes in Parkinson's disease

Dopamine (DA) transporter (DAT) imaging has been studied as a diagnostic tool for degenerative parkinsonism. Our aim was to measure the prognostic value of imaging for motor and nonmotor outcomes in Parkinson's disease (PD). We prospectively evaluated a Parkinson's cohort after enrollment in a de novo clinical trial with a battery of motor (UPDRS), cognitive (Montreal Cognitive Assessment), and behavioral measures. DAT imaging with [¹²³I][β]‐CIT and single‐photon emission computerized tomography (SPECT) was performed at baseline and after 22 months. In total, 491 (91%) of the 537 subjects had evidence of DA deficiency on their baseline scan, consistent with PD, and were included in the analyses. The cohort was followed for 5.5 (0.8) years, with a mean duration of diagnosis of 6.3 (1.2). Lower striatal binding at baseline was independently associated with higher risk for clinical milestones and measures of disease severity, including motor‐related disability, falling and postural instability, cognitive impairment, psychosis, and clinically important depressive symptoms. Subjects in the bottom quartile for striatal binding, compared to the top quartile, had an odds ratio (95% confidence interval) of 3.3 (1.7, 6.7) for cognitive impairment and 12.9 (2.6, 62.4) for psychosis. Change from baseline in imaging after 22 months was also independently associated with motor, cognitive, and behavioral outcomes. DAT imaging with [¹²³I][β]‐CIT and SPECT, shortly after the diagnosis of PD, was independently associated with clinically important long‐term motor and nonmotor outcomes. These results should be treated as hypothesis generating and require confirmation. © 2012 Movement Disorder Society     

Resting‐state functional connectivity of the striatum in early‐stage Parkinson's disease: Cognitive decline and motor symptomatology

Parkinson's disease is a neurodegenerative disorder characterized by changes to dopaminergic function in the striatum and a range of cognitive and motor deficits. Neuroimaging studies have repeatedly shown differences in activation and functional connectivity patterns of the striatum between symptomatic individuals with Parkinson's disease and healthy controls. However, the presence and severity of cognitive and motor symptoms seem to differ dramatically among individuals with Parkinson's disease at the early‐stages. To investigate the neural basis of such heterogeneity, we examined the resting state functional connectivity patterns of caudate and putamen subdivisions in relation to cognitive and motor impairments among 62 early‐stage individuals with Parkinson's disease (21 females, 23 drug naive, ages 39–77 years, average UPDRS motor scores off medication = 18.56, average H&Y stage = 1.66). We also explored how changes in striatal connectivity relate to changes in symptomatology over a year. There are two main findings. First, higher motor deficit rating was associated with weaker coupling between anterior putamen and midbrain including substantia nigra. Intriguingly, steeper declines in functional connectivity between these regions were associated with greater declines in motor function over the course of 1 year. Second, decline in cognitive function, particularly in the memory and visuospatial domains, was associated with stronger coupling between the dorsal caudate and the rostral anterior cingulate cortex. These findings remained significant after controlling for age, medication, gender, and education. In sum, our findings suggest that cognitive decline and motor deficit are each associated with a differentiable pattern of functional connectivity of striatal subregions. Hum Brain Mapp 37:648–662, 2016. © 2015 Wiley Periodicals, Inc.     

How well do caregivers detect mild cognitive change in Parkinson's disease?

Using the Cambridge Behavior Inventory‐Revised, this study evaluated the relationship between caregiver ratings of cognitive change and neuropsychological performance. In sixty‐one nondemented patients with Parkinson's Disease (PD; mean age = 64.5 years, MMSE = 28.7), 62% met criteria for mild cognitive impairment. This group were rated as having more overall change as well as memory and behavior change. Caregiver ratings were related to poorer psychomotor speed, learning/memory, language, and executive functioning. The capacity for caregivers to rate mild cognitive change in PD may be useful to assist in early screening and intervention approaches. © 2010 Movement Disorder Society     

A divergent breakdown of neurocognitive networks in Parkinson's Disease mild cognitive impairment

Cognitive decline is a major disabling feature in Parkinson's disease (PD). Multimodal imaging studies have shown functional disruption in neurocognitive networks related to cognitive impairment. However, it remains unknown whether these changes are related to gray matter loss, or whether they outline network vulnerability in the early stages of cognitive impairment. In this work, we intended to assess functional connectivity and graph theoretical measures and their relation to gray matter loss in Parkinson's disease with mild cognitive impairment (PD‐MCI). We recruited 53 Parkinson's disease patients and classified them for cognitive impairment using Level‐1 Movement Disorders Society‐Task Force Criteria. Voxel‐based morphometry, functional connectivity and graph theoretical measures were obtained on a 3‐Tesla MRI scanner. Loss of gray matter was observed in the default mode network (bilateral precuneus), without a corresponding disruption of functional or graph theoretical properties. However, functional and graph theoretical changes appeared in salience network nodes, without evidence of gray matter loss. Global cognition and executive scores showed a correlation with node degree in the right anterior insula. We also found a correlation between visuospatial scores and right supramarginal gyrus node degree. Our findings highlight the loss of functional connectivity and topological features without structural damage in salience network regions in PD‐MCI. They also underline the importance of multimodal hubs in the transition to mild cognitive impairment. This functional disruption in the absence of gray matter atrophy suggests that the salience network is a key vulnerable system at the onset of mild cognitive impairment in PD.     

Cognitive‐nigrostriatal relationships in de novo,drug‐naïve Parkinson's disease patients: A [I‐123]FP‐CIT SPECT study

To unveil cognitive‐nigrostriatal correlations in Parkinson's disease (PD), 30 de novo, drug‐naïve PD patients and 15 patients with essential tremor (Controls, CTR) underwent a neuropsychological (NPS) battery and brain SPECT with [I‐123]Ioflupane, as a biomarker of nigrostriatal function. Automatic extraction of uptake at caudate and putamen level was conducted through the BasGan software, also allowing partial volume effect correction. Because of the multicollinearity among neuropsychological tests and among SPECT variables, factor analysis was applied to 16 neuropsychological scores; moreover, the four SPECT variables were merged into a mean SPECT value (mSPECT). Factor analysis identified four NPS factors: a dys‐executive (NPS‐EX), a visuospatial (NPS‐VS), a verbal memory (NPS‐VM), and a “mixed” (NPD‐MIX) factor. In PD group, there were inverse correlations between UPDRS‐III score and both NPS‐VS (P < 0.01) and mSPECT (P < 0.05), and a direct correlation between mSPECT and NPS‐EX (P < 0.05). Post hoc analysis showed a direct correlation between NPS‐EX and caudate uptake in both hemispheres (P < 0.05). Moreover, inverse correlations were found between UPDRS‐III and, respectively, putamen uptake in the less affected hemisphere (P < 0.01), and putamen and caudate uptake in the more affected hemisphere (P < 0.05). In CTR, no correlation was found between mSPECT and either NPS or GDS values. Nigro‐caudate function affects executive capabilities in PD but not in CTR, which appears to be unrelated to the disease motor severity at its onset. Instead, PD motor severity is related to nigro‐putaminal impairment and visuospatial dysfunction. The role of these data as predictive features of cognitive decline and eventually dementia remains to be established in longitudinal studies. © 2010 Movement Disorder Society     

Gait patterns in parkinsonian patients with or without mild cognitive impairment

Although in recent years the relationship between cognition and gait in Parkinson's disease (PD) has received increasing attention, the specific connections between gait patterns and cognitive features are not fully understood. The objective of this study was to describe the gait patterns in patients affected by PD with or without mild cognitive impairment (MCI+ and MCI?, respectively). We also sought to find an association between gait patterns and specific cognitive profiles. Using a gait analysis system, we compared the gait patterns among MCI+ patients (n = 19), MCI? patients (n ? 24), and age‐ and sex‐matched healthy subjects (HS; n = 20) under the following conditions: (1) normal gait, (2) motor dual task, and (3) cognitive dual task. In PD patients, gait parameters were evaluated in both the off and on states. Memory, executive, and visuospatial domains were assessed using an extensive neuropsychological battery. Compared with MCI? PD and HS, MCI+ PD patients displayed reduced step length and swing time and impairment of measures of dynamic stability; these dysfunctions were only partially reversed by levodopa. We also found that dual‐task conditions affected several walking parameters in MCI+ PD in the off and on states relative to MCI? PD and HS. Factor analysis revealed 2 independent factors, namely, pace and stability. The latter was strongly and directly correlated to the visuospatial domain. In conclusion, dysfunctions on specific gait parameters, which were poorly responsive to levodopa and highly sensitive to dual‐task conditions, were associated with MCI in PD patients. Importantly, visuospatial impairment was strongly associated with the development of instability and more generally with the progression of PD. © 2012 Movement Disorder Society     

Cortical thinning associated with mild cognitive impairment in Parkinson's disease

The aim of this study was to investigate patterns of cortical atrophy associated with mild cognitive impairment in a large sample of nondemented Parkinson's disease (PD) patients, and its relation with specific neuropsychological deficits. Magnetic resonance imaging (MRI) and neuropsychological assessment were performed in a sample of 90 nondemented PD patients and 32 healthy controls. All underwent a neuropsychological battery including tests that assess different cognitive domains: attention and working memory, executive functions, memory, language, and visuoperceptual‐visuospatial functions. Patients were classified according to their cognitive status as PD patients without mild cognitive impairment (MCI; n = 43) and PD patients with MCI (n = 47). Freesurfer software was used to obtain maps of cortical thickness for group comparisons and correlation with neuropsychological performance. Patients with MCI showed regional cortical thinning in parietotemporal regions, increased global atrophy (global cortical thinning, total gray matter volume reduction, and ventricular enlargement), as well as significant cognitive impairment in memory, executive, and visuospatial and visuoperceptual domains. Correlation analyses showed that all neuropsychological tests were associated with cortical thinning in parietotemporal regions and to a lesser extent in frontal regions. These results provide neuroanatomic support to the concept of MCI classified according to Movement Disorders Society criteria. The posterior pattern of atrophy in temporoparietal regions could be a structural neuroimaging marker of cognitive impairment in nondemented PD patients. All of the neuropsychological tests reflected regional brain atrophy, but no specific patterns were seen corresponding to impairment in distinct cognitive domains. © 2014 International Parkinson and Movement Disorder Society     

Cognitive Impairment in Parkinson's Disease without Dementia: Subtypes and Influences of Age

Background and Purpose

Cognitive impairments are common in Parkinson''s disease (PD), although the severity of these impairments does not significantly impair the patient''s daily activities. The aim of this study was to determine the frequency of mild cognitive impairment (MCI) of Parkinson''s disease (PDMCI) and its subtypes in nondemented PD patients. We also evaluated the influence of age on the pattern of subtypes of PDMCI.

Methods

A total of 141 consecutive, nondemented PD patients underwent a comprehensive neuropsychological assessment covering the five cognitive domains: attention, language, visuospatial, memory, and executive functions. PDMCI was defined as impaired performance in at least one of these five cognitive domains. The influence of age on the distribution of subtypes of PDMCI was assessed by comparing patients in two groups dichotomized according to their age at assessment (younger vs. older).

Results

Fifty-seven (40.4%) of the nondemented PD patients had an impairment in at least one domain, and were therefore considered as having PDMCI. The age at assessment and age at disease onset were significantly higher in the PDMCI patients. The amnestic type of PDMCI was the most frequent, followed by the visuospatial, linguistic, executive, and attention types in that order. The frequency of PDMCI was higher for all subtypes in the older group; the domain that was influenced the most by age was executive function.

Conclusions

MCI was common in PD and the subtypes were diverse. Age was found to be an important risk factor for the development of PDMCI, particularly for the executive subtype. These results indicate that the concept of MCI should be introduced in PD.     

Dissociations among daytime sleepiness,nighttime sleep,and cognitive status in Parkinson's disease

BackgroundDaytime and nighttime sleep disturbances and cognitive impairment occur frequently in Parkinson's disease (PD), but little is known about the interdependence of these non-motor complications. Thus, we examined the relationships among excessive daytime sleepiness, nighttime sleep quality and cognitive impairment in PD, including severity and specific cognitive deficits.MethodsNinety-three PD patients underwent clinical and neuropsychological evaluations including the Epworth Sleepiness Scale (ESS) and Pittsburgh Sleep Quality Index (PSQI). Patients were classified as having normal cognition (PD-NC), mild cognitive impairment (PD-MCI), or dementia (PDD) using recently proposed Movement Disorder Society PD-MCI and PDD criteria. Relationships between the sleep and cognitive measures and PD cognitive groups were examined.ResultsThe PD cohort included PD-NC (n = 28), PD-MCI (n = 40), and PDD (n = 25) patients. ESS scores, as a measure of daytime sleepiness, were significantly worse (p = 0.005) in cognitively impaired PD patients, particularly PDD patients. ESS scores correlated significantly with Mini-Mental State Examination scores and also with cognitive domain scores for attention/working memory, executive function, memory, and visuospatial function. In contrast, PSQI scores, as a measure of nighttime sleep quality, neither differed among cognitive groups nor correlated with any cognitive measures.ConclusionsDaytime sleepiness in PD, but not nighttime sleep problems, is associated with cognitive impairment in PD, especially in the setting of dementia, and attention/working memory, executive function, memory, and visuospatial deficits. The presence of nighttime sleep problems is pervasive across the PD cognitive spectrum, from normal cognition to dementia, and is not independently associated with cognitive impairment or deficits in cognitive domains.     

Gastrointestinal symptoms are predictive of trajectories of cognitive functioning in de novo Parkinson's disease

IntroductionNon-motor symptoms such as cognitive and gastrointestinal (GI) symptoms are common in Parkinson's disease (PD). In PD, GI-symptoms often present prior to motor symptoms. It is hypothesized that GI-symptoms reflect disruptions of the microbiome-gut-brain axis, which leads to altered immune functioning, chronic neuroinflammation, and subsequent neurodegeneration. Initial evidence links gut-dysbiosis to PD pathology and motor symptom severity. The present study examines the longitudinal relationship between severity of GI-symptoms and cognitive impairment in newly diagnosed PD patients.MethodsA secondary data analysis of the Parkinson's Progression Markers Initiative (PPMI) included 423 newly diagnosed PD patients who were followed for up to 5 years. Participants underwent neuropsychological tests of processing speed, attention, visuospatial functioning, verbal learning and verbal delayed recall. Participant were classified as cognitive intact, mild cognitive impairment or Parkinson's disease dementia. Frequency of GI-symptoms were assessed with the Scales for Outcomes in Parkinson's Disease Autonomic (SCOPA-AUT). Multi-level models (MLM) examined the longitudinal relationship between GI symptoms and cognitive impairment.ResultsAll cognitive outcomes were predicted by the main effect of GI symptoms, or the GI-symptom X Occasion interaction term. Specifically, more severe GI-symptoms were predictive of a less favorable trajectory of performance on tests of letter fluency, visuospatial, learning and memory. Cognitive performance was uniquely associated with GI-symptoms and unrelated to non-GI autonomic symptoms.ConclusionsThe presence of GI symptoms may serve as an early marker of cognitive impairment in PD. Future studies should examine specific mechanisms underlying the relationship between gut-dysbiosis and cognitive impairment.     

People with Parkinson's disease and normal MMSE score have a broad range of cognitive performance

Cognitive impairment, including dementia, is common in Parkinson's disease (PD). The Mini‐Mental State Examination (MMSE) has been recommended as a screening tool for Parkinson's disease dementia (PDD), with values below 26 indicative of possible dementia. Using a detailed neuropsychological battery, we examined the range of cognitive impairment in PD patients with an MMSE score of 26 or higher. In this multicenter, cross‐sectional, observational study, we performed neuropsychological testing in a sample of 788 PD patients with MMSE scores of 26 or higher. Evaluation included tests of global cognition, executive function, language, memory, and visuospatial skills. A consensus panel reviewed results for 342 subjects and assigned a diagnosis of no cognitive impairment, mild cognitive impairment, or dementia. Sixty‐seven percent of the 788 subjects performed 1.5 standard deviations below the normative mean on at least one test. On eight of the 15 tests, more than 20% of subjects scored 1.5 standard deviations or more below the normative mean. Greatest impairments were found on Hopkins Verbal Learning and Digit Symbol Coding tests. The sensitivity of the MMSE to detect dementia was 45% in a subset of participants who underwent clinical diagnostic procedures. A remarkably wide range of cognitive impairment can be found in PD patients with a relatively high score on the MMSE, including a level of cognitive impairment consistent with dementia. Given these findings, clinicians must be aware of the limitations of the MMSE in detecting cognitive impairment, including dementia, in PD. © 2014 International Parkinson and Movement Disorder Society     

Striato‐cortical connections in Parkinson's and Alzheimer's diseases: Relation to cognition

Background : Functional connectivity is abnormal in PD and in early Alzheimer's disease. Objectives : The objective of this study was to evaluate resting‐state striato‐cortical connectivity in PD and Alzheimer's disease and assess their relation to cognitive outcomes. Groups with mild cognitive impairment as a result of different pathologies (PD vs. Alzheimer's disease) were also compared. Methods : Seed‐based connectivity of the dorsal, middle, and ventral striatum was analyzed in 111 patients using functional MRI. The correlation between connectivity at regions of between‐group differences and clinical outcomes was assessed. Results : Patients showed lower striatal connectivity than controls. Connectivity between the middle (associative) striatum and precuneus negatively correlated with executive functions in PD and with memory performance in Alzheimer's disease. PD with cognitive impairment showed decreased connectivity of the dorsal (motor) striatum when compared with early Alzheimer's disease. Conclusions : Striatal connectivity was reduced in patients when compared with controls. Similar compensatory mechanisms were employed to overcome various cognitive deficits in PD and Alzheimer's disease. © 2017 International Parkinson and Movement Disorder Society     

Functional brain networks and cognitive deficits in Parkinson's disease

Graph‐theoretical analyses of functional networks obtained with resting‐state functional magnetic resonance imaging (fMRI) have recently proven to be a useful approach for the study of the substrates underlying cognitive deficits in different diseases. We used this technique to investigate whether cognitive deficits in Parkinson's disease (PD) are associated with changes in global and local network measures. Thirty‐six healthy controls (HC) and 66 PD patients matched for age, sex, and education were classified as having mild cognitive impairment (MCI) or not based on performance in the three mainly affected cognitive domains in PD: attention/executive, visuospatial/visuoperceptual (VS/VP), and declarative memory. Resting‐state fMRI and graph theory analyses were used to evaluate network measures. We have found that patients with MCI had connectivity reductions predominantly affecting long‐range connections as well as increased local interconnectedness manifested as higher measures of clustering, small‐worldness, and modularity. The latter measures also tended to correlate negatively with cognitive performance in VS/VP and memory functions. Hub structure was also reorganized: normal hubs displayed reduced centrality and degree in MCI PD patients. Our study indicates that the topological properties of brain networks are changed in PD patients with cognitive deficits. Our findings provide novel data regarding the functional substrate of cognitive impairment in PD, which may prove to have value as a prognostic marker. Hum Brain Mapp 35:4620–4634, 2014. © 2014 Wiley Periodicals, Inc .     

Catechol‐O‐methyltransferase val158met and cognitive function in Parkinson's disease

Cognitive dysfunction is one of the most incapacitating non‐motor symptoms of Parkinson's disease (PD). Some cognitive deficits are thought to be related to abnormal dopamine homeostasis. The latter is influenced by catechol‐O‐methyltransferase (COMT), an enzyme that degrades dopamine. Previous research suggests a relationship between the COMT val158met functional polymorphism (SNP) and measures of executive function. We evaluated this hypothesis in a cohort of PD patients with an extensive neuropsychological test battery. Cognitive assessment and COMT genotyping were performed in 153 early PD patients from outpatient clinics general hospitals in the Netherlands. Our results do not support a direct effect of COMT val158met genotype on performance on neuropsychological measures of attention and executive function, but they suggest that genotype may interact with dopaminergic medication use to influence cognitive ability. © 2010 Movement Disorder Society