Is all cognitive impairment in Parkinson’s disease “mild cognitive impairment”?

Cognitive impairment can be demonstrated in Parkinson’s disease (PD) from the very beginning of the disease. Clinical manifestations range from slight deficits, only demonstrable by means of neuropsychological testing, up to dementia. If a linear involution is supposed for the cognitive worsening in PD, then the relatively subtle cognitive defects should be taken as the earliest signs of dementia implying that PD-MCI concept would be thoroughly equivalent to that used for the early prediction of other dementias among healthy population. Cognitive defects in PD, however, may not follow a normal distribution. While fronto-striatal deficits, such as working memory, set-shifting and free-recall verbal memory appear altered in most patients during long periods of time, certain functions depending on more posterior-cortical regions, such as copying or naming, usually characterize patients with dementia. Fronto-striatal and posterior-cortical cognitive defects may have a different pathophysiological substrates, evolution and prognosis. While fronto-striatal defects appear more related to dopaminergic defects, posterior-cortical defects may obey multiple neurotransmitter failure. Designing criteria to accurately diagnose PD-MCI is highly relevant for clinical treatment, research, care-giving and decision-making. Besides quantitative defects, an operative definition of MCI in PD should clearly distinguish a “risky cognitive profile” among the broad cognitive defects intrinsic to PD. Thus, along with other possible biological markers, from a neuropsychological point of view, posterior-cortical defects probably represent the very syndrome of MCI in PD.     

Heterogenous mechanisms of mild cognitive impairment in Parkinson’s disease

Mild cognitive impairment in Parkinson disease (PD-MCI) shows heterogeneity in the clinical presentation, neuropsychology, neuroimaging, and neuropathology, suggesting abnormal metabolic network activities involving several cortical and subcortical systems. Prospective studies using specific biomarkers, including amyloid imaging and CSF biomarkers are important for the diagnosis and prognostic assessment of early cognitive deficits in PD patients.     

Mild cognitive impairment in Parkinson’s disease

Parkinson’s disease (PD) has initially been described as a clinical syndrome, although its exact definition has changed over the past centuries. The identification of the pathological changes added another level of complexity, with Lewy bodies, synuclein deposits and neuronal loss in the substantia nigra being used alternatively as criteria. A third level of complexity was added with the recognition of genetic mutations resulting in Parkinsonism, sometimes with and sometimes without Lewy bodies or synuclein deposition. Lastly, frequent additional important pre-motor manifestations, particularly depression, anosmia and sleep-associated phenomena have been described. These different points of view on the definition of PD have important implications on the study of the etiology and even the therapy of PD. Cognitive impairment is also an important feature of PD, while the spectrum of deficits ranges from none to severe dementia. The no-man land in-between normal cognition and dementia has been termed mild cognitive impairment in PD. At present, this term lacks heuristic value or clinical utility, and remains a target for scientific research.     

False memories in patients with mild cognitive impairment and mild Alzheimer’s disease dementia: Can cognitive strategies help?

Alzheimer’s disease (AD) is a progressive neurodegenerative disorder that presents predominantly with impairments in learning and memory. Patients with AD are also susceptible to false memories, a clinically relevant memory distortion where a patient remembers an incorrect memory that they believe to be true. The use of cognitive strategies to improve memory performance among patients with AD by reducing false memories has taken on added importance given the lack of disease-modifying agents for AD. However, existing evidence suggests that cognitive strategies to reduce false memories in patients with AD are of limited effectiveness, although these strategies may be useful at earlier stages of the disease. The purpose of this review is to examine experimental findings of false memories and associated memory processes in patients with mild cognitive impairment due to AD and mild AD dementia. Cognitive strategies to reduce false memories in these patient populations are also reviewed. Approaches to clinically relevant future research are suggested and discussed.     

Identifying subtypes of mild cognitive impairment in Parkinson’s disease using cluster analysis

Journal of Neurology - The concept of Mild Cognitive Impairment (MCI) in Parkinson’s disease (PD) has shown the potential for identifying at-risk dementia patients. Identifying subtypes of...     

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.     

Differential functional connectivity of insular subdivisions in de novo Parkinson’s disease with mild cognitive impairment

Brain Imaging and Behavior - The insula, consisting of functionally diverse subdivisions, plays a significant role in Parkinson’s disease (PD)-related cognitive disorders. However, the...     

The new Alzheimer’s criteria in a naturalistic series of patients with mild cognitive impairment

To test the validity of the new diagnostic criteria for Alzheimer’s disease (AD) in a naturalistic series of patients with mild cognitive impairment (MCI). Ninety consecutive MCI patients were enrolled in a longitudinal study on the natural history of cognitive impairment. Medial temporal (MT) atrophy on MRI was defined as hippocampal volume below the fifth percentile of the distribution in healthy elders, abnormal CSF was based on Sjogren’s cutoffs for Abeta42 and tau, and temporoparietal hypometabolism on 18F-FDG PET based on Herholz’s t sum score. Patients were followed clinically to detect conversion to AD (MCI-AD), non-AD dementia (MCI-nAD), or no conversion (MCI-NC). The 24 MCI-AD and 15 MCI-nAD patients had sociodemographic, clinical, and neuropsychological baseline features similar to the 51 MCI-NC patients. All MCI patients with MT atrophy converted to AD, as did all those with abnormal CSF, but only 48 and 35% of those without MT atrophy or abnormal CSF converted (p on logrank test = 0.0007 and 0.001). Prediction of AD conversion was enhanced when positivity to either MT atrophy or abnormal CSF was considered, with only 15% of those MCI patients negative on both converting to AD (p < 0.0005). Markers were not predictive of non-AD dementia conversion. The accuracy of either MT atrophy or abnormal CSF in discriminating MCI-AD from MCI-NC was good (AUC 0.82, 95% CI 0.70–0.95). MT atrophy and abnormal CSF are the single most robust predictors of conversion to AD in MCI patients, and their combination enhances prediction. AD markers are not predictive of conversion to non-AD dementia.     

Local susceptibility causes diffusion alterations in patients with Alzheimer’s disease and mild cognitive impairment

Recent studies with positron emission tomography (PET) using the Pittsburgh compound B (PIB) found widespread amyloid plaque depositions in patients with Alzheimer’s disease (AD) and mild cognitive impairment (MCI) and even in cognitively normal (CN) subjects. The aim of this study was to investigate whether the local susceptibility gradients in brain tissue alter regional diffusion measurements using MRI in patients with AD and MCI. Two diffusion tensor (DT)-MRI data sets were acquired with alternating polarities of the external diffusion-sensitizing gradients. Three subject groups were included: 15 patients with AD, 18 patients with MCI and 16 CN. Maps of mean diffusivity (MD) and fractional anisotropy (FA) were computed separately for positive (p) and negative (n) polarities (pMD and nMD, pFA and nFA). Voxel-wise paired t-tests were performed between pMD versus nMD or between pFA versus nFA maps, separately for each subject group. We also investigated regions-of-interest (ROIs) in the brain. Based on the pair-wise comparisons, we found significant differences between pMD and nMD in all three groups. Results of ROI-based analyses showed that the non-linear behaviors of the ROI data sets were shown for all three groups. In conclusion, significant differences of MD maps between the two polarities of diffusion-sensitizing gradients were found, suggesting that the intrinsic background gradients may alter MD signals in specific regions. It can be important to take into account the effects of local gradient alterations during diffusion measurements in patients with AD, MCI and elderly controls.     

The neuropsychiatric profile of Parkinson’s disease subjects with and without mild cognitive impairment

Neuropsychiatric symptoms (NPS) are common clinical features of Parkinson’s disease (PD). However, NPS profiles in PD subjects with mild cognitive impairment (MCI) have scarcely been investigated. We aimed to describe the NPS profiles of non-demented PD subjects with and without MCI. A total of 410 non-demented PD subjects were included. Of these, 164 were cognitively normal PD subjects (PD-cn), 142 PD had amnestic MCI (PD-aMCI), and 104 had PD with non-amnestic MCI (PD-naMCI). NPS were evaluated in accordance with the Neuropsychiatric Inventory (NPI). PD-aMCI subjects revealed the highest NPS burden, followed by PD-naMCI and then PD-cn. Overall, the most common NPS in PD-MCI were in order: depression, sleep disturbance, anxiety and apathy. Irritability was significantly associated with PD-aMCI and PD-naMCI. Prospective studies are required to evaluate the significance, clinical correlates and prognostic role of NPS in subject with PD-MCI.     

Taste in mild cognitive impairment and Alzheimer’s disease

In this prospective study we investigated the quantitative and qualitative taste function of patients with mild cognitive impairment (MCI) and Alzheimer’s disease (AD). 29 healthy, elderly subjects, 29 MCI and 30 AD patients were tested using a validated taste test, the “taste strips”. Additionally, odor identification, odor discrimination, odor threshold, the mini-mental state examination (MMSE) and Apo E epsilon 4 status were examined. Regarding taste, there was a significant reduction of total taste scores and also the score for individual tastes on either side of the tongue between controls and MCI/AD patients. There was no significant difference in the taste scores between MCI and AD patients. A taste test may be a useful procedure for differentiating between healthy subjects and patients with MCI/AD in a clinical context. For diagnosing MCI versus AD, further tests such as smell test, MMSE, Apo E epsilon 4 status, FDG-PET and MRI appear to be useful.     

Independent effect of neurogenic orthostatic hypotension on mild cognitive impairment in Parkinson’s disease

Clinical Autonomic Research - Orthostatic hypotension (OH) is an associative or causative factor of cognitive impairment in Parkinson’s disease (PD). However, the association between mild...     

Effects of happy and sad facial expressions on the perception of time in Parkinson’s disease patients with mild cognitive impairment

Introduction: Parkinson’s disease (PD) is a movement disorder caused by deterioration of the dopaminergic system. Previous studies have demonstrated temporal as well as emotional facial recognition impairment in PD patients. Moreover, it has been demonstrated that emotional facial expressions alter temporal judgments. In the present study, we investigate the magnitude of temporal distortions caused by the presentation of emotional facial expressions (happiness, sadness, and neutral) in PD patients with mild cognitive impairment (PD-MCI) and controls.

Method: Seventeen older adults with PD-MCI and 22 healthy older adults took part in the present study. Participants were tested with a time bisection task with standard intervals lasting 400 ms and 1600 ms. Moreover, a complete neuropsychological evaluation was conducted to characterize the sample.

Results: Differences between groups were observed indicating a general underestimation of time in PD-MCI patients. Temporal impairments in PD-MCI patients seem to be caused mainly by a dysfunction at the level of reference memory. The effect of emotional facial expressions on time perception was evident in both PD patients and controls, with an overestimation of perceived duration when happiness was presented and an underestimation when sadness was presented.

Conclusion: Overall, our results indicate that reduced cognitive abilities might be responsible for the lower temporal ability observed in PD-MCI patients. Moreover, similar effects of emotional stimuli were observed in both PD-MCI patients and controls.     

The pattern of cortical atrophy in Parkinson’s disease with mild cognitive impairment according to the timing of cognitive dysfunction

The density of Lewy bodies or the concurrent β-amyloid pathology would act as modulators in the relative timing of dementia during the course of Parkinson’s disease. Depending on the temporal relationship between the onset of parkinsonism and that of cognitive impairment, patients with Parkinson’s disease with mild cognitive impairment were divided into two groups of earlier (<1 year) and later (≥1 year) cognitive decline, and cortical atrophy patterns and correlation of gray matter and timing of cognitive decline were analyzed using voxel-based morphometry. The morphometric analysis showed that patients with earlier cognitive decline demonstrated greater cortical atrophy in the inferior parietal and orbitofrontal areas than did those with later cognitive decline. Additionally, the anatomical bases of the timing of their cognitive decline differed in terms of correlation patterns. These data suggest that the pathological burden in Parkinson’s disease with mild cognitive impairment may be more severe in patients with earlier cognitive decline than in those with later cognitive decline, and that the neural basis corresponding to the timing of cognitive decline may differ in these patients.