Katharina Linse

Subtypes of mild cognitive impairment in patients with Parkinson's disease: evidence from the LANDSCAPE study

Objective Inconsistent results exist regarding the cognitive profile in patients with Parkinsons disease with mild cognitive impairment (PD-MCI). We aimed at providing data on this topic from a large cohort of patients with PD-MCI. Methods Sociodemographic, clinical and neuropsychological baseline data from patients with PD-MCI recruited in the multicentre, prospective, observational DEMPARK/LANDSCAPE study were analysed. Results 269 patients with PD-MCI (age 67.8±7.4, Unified Parkinsons Disease Rating Scale (UPDRS-III) scores 23.2±11.6) were included. PD-MCI subtypes were 39.4% non-amnestic single domain, 30.5% amnestic multiple domain, 23.4% non-amnestic multiple domain and 6.7% amnestic single domain. Executive functions were most frequently impaired. The most sensitive tests to detect cognitive dysfunctions were the Modified Card Sorting Test, digit span backwards and word list learning direct recall. Multiple stepwise regression analyses showed that global cognition, gender and age, but not education or disease-related parameters predicted PD-MCI subtypes. Conclusions This study with the so far largest number of prospectively recruited patients with PD-MCI indicates that non-amnestic PD-MCI is more frequent than amnestic PD-MCI; executive dysfunctions are the most typical cognitive symptom in PD-MCI; and age, gender and global cognition predict the PD-MCI subtype. Longitudinal data are needed to test the hypothesis that patients with PD-MCI with specific cognitive profiles have different risks to develop dementia.

Eyetracking-based assessment suggests preserved wellbeing in locked-in patients

We assessed quality of life (QoL) and psychological well‐being in patients with amyotrophic lateral sclerosis–induced locked‐in state and their next of kin in a fully unbiased manner using eye‐tracking computer systems. Eleven of 30 screened patients and 9 next of kin completed study procedures. Patients reported good QoL, which appeared to be at the cost of the QoL of their next of kin. Next of kin rated their own or patients’ QoL similarly, but they identified different areas as important as compared with patients. Our results are of importance for the discussion of end‐of‐life decisions and the evaluation of patients’ presumed wishes as well as for psychosocial interventions. Ann Neurol 2017;81:310–315

Accelerated Age-Dependent Hippocampal Volume Loss in Parkinson Disease With Mild Cognitive Impairment

Background: Patients with Parkinson disease are at high risk of developing dementia. During the course of the disease, a substantial number of patients will experience a cognitive decline, indicating the dynamics of the underlying neuropathology. Magnetic resonance imaging (MRI) has become increasingly useful for identifying structural characteristics in radiological brain anatomy existing prior to clinical symptoms. Whether these changes reflect pathology, whether they are aging related, or both often remains unclear. We hypothesized that aging-associated brain structural changes would be more pronounced in the hippocampal region among patients with Parkinson disease having mild cognitive deficits relative to cognitively unimpaired patients. Methods: Using MRI, we investigated 30 cognitively healthy patients with Parkinson disease and 33 patients with nondemented Parkinson disease having mild cognitive impairment. All participants underwent structural MRI scanning and extensive clinical and neuropsychological assessments. Results: Irrespective of the study participants’ cognitive status, older age was associated with reduced cortical thickness in various neocortical regions. Having mild cognitive impairment was not associated with an increased rate of cortical thinning or volume loss in these regions, except in the hippocampus bilaterally. Conclusion: Patients with Parkinson disease having mild cognitive impairment show an accelerated age-dependent hippocampal volume loss when compared with cognitively healthy patients with Parkinson disease. This may indicate pathological processes in a key region for memory functioning in patients with Parkinson disease at risk of developing dementia. Structural MRI of the hippocampal region could potentially contribute to identifying patients who should receive early treatment aimed at delaying the clinical onset of dementia.

Verbal memory declines more in female patients with Parkinson's disease: the importance of gender-corrected normative data.

BACKGROUND Data on gender-specific profiles of cognitive functions in patients with Parkinsons disease (PD) are rare and inconsistent, and possible disease-confounding factors have been insufficiently considered. METHOD The LANDSCAPE study on cognition in PD enrolled 656 PD patients (267 without cognitive impairment, 66% male; 292 with mild cognitive impairment, 69% male; 97 with PD dementia, 69% male). Raw values and age-, education-, and gender-corrected Z scores of a neuropsychological test battery (CERAD-Plus) were compared between genders. Motor symptoms, disease duration, l-dopa equivalent daily dose, depression - and additionally age and education for the raw value analysis - were taken as covariates. RESULTS Raw-score analysis replicated results of previous studies in that female PD patients were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.03), while men outperformed women in visuoconstruction (p = 0.002) and figural memory (p = 0.005). In contrast, gender-corrected Z scores showed that men were superior in verbal memory (word list learning, p = 0.02; recall, p = 0.02; recognition, p = 0.04), while no difference was found for visuospatial tests. This picture could be observed both in the overall analysis of PD patients as well as in a differentiated group analysis. CONCLUSIONS Normative data corrected for gender and other sociodemographic variables are relevant, since they may elucidate a markedly different cognitive profile compared to raw scores. Our study also suggests that verbal memory decline is stronger in women than in men with PD. Future studies are needed to replicate these findings, examine the progression of gender-specific cognitive decline in PD and define different underlying mechanisms of this dysfunction.

Psychometric properties of the apathy evaluation scale in patients with Parkinson's disease

Parkinsons disease (PD) frequently entails non‐motor symptoms, worsening the course of the disease. Apathy is one of the core neuropsychiatric symptoms that has been investigated in recent years; research is however hampered by the limited availability of well‐evaluated apathy scales for these patients. We evaluated the psychometric properties of the Apathy Evaluation Scale (AES) in a sample of PD patients. Psychometric properties, convergent and discriminant validity and sensitivity/specificity were evaluated in patients with (n = 582) or without dementia/depression (n = 339). Internal consistency was high in the entire sample as well as in patients without dementia/depression. Correlations were moderate for convergent validity (UPDRS I item 4: motivation). While apathy could be differentiated from cognitive decline, it was related to depression (Geriatric Depression Scale, GDS‐15). The overall classification accuracy based on the UPDRS I item 4 was comparable for AES and GDS scores. The AES exhibits good psychometric properties in PD patients with and without dementia and/or depression. Commonly used screenings on the presence of apathy had low detection rates compared to the AES and reflected both apathetic and depressive symptoms. Psychometric evaluation of available instruments will support further research on the clinical relevance of apathy for disease progression and treatment approaches in PD patients.

Usability of eyetracking computer systems and impact on psychological wellbeing in patients with advanced amyotrophic lateral sclerosis

Abstract Restrictions in communicative abilities are well known in patients with amyotrophic lateral sclerosis (ALS), but only few approaches in terms of evaluation of supportive technologies have been made. We aimed to assess the use and perceived usability of eye-tracking computer devices (ETCS) of severely impacted patients with ALS in an independent, direct manner and relate it to psychological well-being. ETCS enable active communication and social participation in the quadriplegic and anarthric disease state. Therefore, ETCS-based versions of widely used psychosocial questionnaires (ADI-12, SeiQoL-DW, WHO-5) as well as structured questions on communicative functioning and ETCS usage were developed to assess ALS patients, their next of kin and professional caregivers. Eleven patients (ALSFRS-R: 5.3 ± 5.9; ALS duration: 6.5 ± 3.8 years, range 1‒12; 82% invasively ventilated), nine next of kin and 10 professional caregivers could be assessed. Patients reported a mean use of their personal ETCS of 9.1 h per d (range 0.5‒16), with a high user satisfaction, preservation of communicative abilities and subjective indispensability of the ETCS. ETCS use was associated with higher psychological well-being. Next of kin and professional caregivers also nominated some critical aspect, which remains to be clarified. Our results strengthen the evidence that preserved mental autonomy influences psychological well-being in ALS and might even modify disease course and end-of-life-decisions in ALS.

Spatial learning deficits in Parkinson's disease with and without mild cognitive impairment

BACKGROUND Several MRI studies have demonstrated hippocampal atrophy in Parkinsons disease (PD), a structure considered a key element in spatial learning. Despite this, no study has been undertaken to investigate spatial navigation in PD using a virtual version of the Morris water maze, which is the gold standard for testing hippocampal function in rodents. METHODS We studied 17 cognitively unimpaired PD patients, 12 PD patients with mild cognitive impairment (MCI) and 15 controls in a virtual water maze procedure. RESULTS Measured by the main outcome parameters latency to locate the target and heading error (average difference between direction of movement toward anticipated target and real direction toward the target), controls performed significantly better on the virtual water maze task than cognitively unimpaired PD patients or PD patients with MCI, while there was no significant difference between latter two groups. CONCLUSIONS The virtual water maze test differentiates PD patients from controls, but does not distinguish between cognitively normal and cognitively impaired PD patients, indicating a possible dopamine dependent component in spatial learning. Spatial performance deficits might thus constitute very early signs of dopamine depletion independent of the presence of MCI in Parkinsons disease.

Reply to Letter to the Editor: “Converse well‐being of locked in patients and caregivers” by S. Renault and A. Dhand.

are well described. However, the study also showed that family members may have adjusted to the situation less quickly; family members assumed that patients had lower quality of life than the patients actually did. These misperceptions have consequences for end-of-life expectations and conversations. Overall, this article is part of a growing literature that stresses the need to expand the understanding of neurological illness to include information on a patient’s social circle. Study of the social effects of neurological health and illness may be enhanced by a personal network approach to map and trend social information in a useful way. The personal network method situates the patient within a social connectome, identifying various individuals and characterizing the nature and strength of their relationship to the patient and to one another (Figure). The network is populated with both kin and nonkin joined by weak and strong ties. It can reveal distinct structural motifs, such as clusters of like-minded individuals, and compositional traits, like the diversity of health habits enveloping the patient, all of which may change over time. Most network analyses have been used to probe patientlevel incidence and outcomes of breast cancer and type 2 diabetes. However, Dr. Linse et al’s study shows the value of studying caregiver perspectives and outcomes separately from patients’ outcomes. Therefore, a network approach could map the network of the patient, map the network of the caregiver(s), and identify structural patterns (eg, shrinking over time) that may differ for the two parties. The approach could be valuable to assess mechanisms of the quality of life and well-being outcomes and their divergence within the social unit. Such network information could lead to network interventions to improve end-of-life care for patients and their loved ones.

Cognitive decline in Parkinson’s disease: the impact of the motor phenotype on cognition

Objectives Parkinson’s disease (PD) is the second most common neurodegenerative disorder and is further associated with progressive cognitive decline. In respect to motor phenotype, there is some evidence that akinetic-rigid PD is associated with a faster rate of cognitive decline in general and a greater risk of developing dementia. The objective of this study was to examine cognitive profiles among patients with PD by motor phenotypes and its relation to cognitive function. Methods Demographic, clinical and neuropsychological cross-sectional baseline data of the DEMPARK/LANDSCAPE study, a multicentre longitudinal cohort study of 538 patients with PD were analysed, stratified by motor phenotype and cognitive syndrome. Analyses were performed for all patients and for each diagnostic group separately, controlling for age, gender, education and disease duration. Results Compared with the tremor-dominant phenotype, akinetic-rigid patients performed worse in executive functions such as working memory (Wechsler Memory Scale-Revised backward; p=0.012), formal-lexical word fluency (p=0.043), card sorting (p=0.006), attention (Trail Making Test version A; p=0.024) and visuospatial abilities (Leistungsprüfungssystem test 9; p=0.006). Akinetic-rigid neuropsychological test scores for the executive and attentive domain correlated negatively with non-tremor motor scores. Covariate-adjusted binary logistic regression analyses showed significant odds for PD-mild cognitive impairment for not-determined as compared with tremor-dominant (OR=3.198) and akinetic-rigid PD (OR=2.059). The odds for PD-dementia were significant for akinetic-rigid as compared with tremor-dominant phenotype (OR=8.314). Conclusion The three motor phenotypes of PD differ in cognitive performance, showing that cognitive deficits seem to be less severe in tremor-dominant PD. While these data are cross-sectional, longitudinal data are needed to shed more light on these differential findings.

Psychometric Properties of an Abbreviated Version of the Apathy Evaluation Scale for Parkinson Disease (AES-12PD)

BACKGROUND Apathy is a frequent symptom in Parkinsons disease (PD), substantially aggravating the course of PD. Regarding the accumulating evidence of the key role of apathy in PD, time-efficient assessments are useful for fostering progress in research and treatment. The Apathy Evaluation Scale (AES) is widely used for the assessment of apathy across different nosologies. OBJECTIVE To facilitate the application of the AES in PD, we reduced the AES to two-thirds its length and validated this abbreviated version. DESIGN Data sets of 339 PD patients of the DEMPARK/LANDSCAPE study without dementia and depression were randomly split into two samples. Data of sample 1 were used to develop a brief version of the AES (AES-12PD). A cross-validation was conducted in sample 2 and in a subsample of 42 PD patients with comorbid dementia and depressive symptomatology. Receiver operating characteristic analysis was applied to determine the optimal cutoff of the AES-12PD as an indicator of apathy. RESULTS The AES-12PD featured high internal consistency that was better compared to the AES. The abbreviated scale was well differentiated from motor impairment and cognitive deficits. The AES-12PD cutoff of 27/28 was the optimal cutoff for apathy in PD patients without dementia and depression. The cutoff of 25/26 indicated apathy in PD patients with comorbid dementia and depression. CONCLUSION Results confirm a high internal consistency and good discriminant validity of the AES-12PD. The AES-12PD represents a reliable tool for the efficient assessment of apathy that can be applied in PD patients with and without dementia and depression.