[Guidelines for the Neuropsychological Assessment of Patients with Parkinson's Disease]. / Empfehlungen zur neuropsychologischen Diagnostik beim Morbus Parkinson.

BACKGROUND: Presence of mild cognitive impairment is currently the best predictor for the development of Parkinson's disease dementia. Diagnostic criteria for both Parkinson's with mild cognitive impairment and Parkinson's disease dementia have been suggested by the Movement Disorder Society. However, not all cognitive tests recommended are available in the German language with proper standard values. OBJECTIVES: To define evidence-based guidelines for neuropsychological assessment of patients with Parkinson's disease in German. METHODS: Two systematic literature searches were conducted. First, articles that presented international guidelines (consensus papers or reviews) for the application of standardized neuropsychological assessments for the diagnosis of cognitive impairment in Parkinson's disease were selected. Of those, only neuropsychological assessments in German language with normative values referring either to a German, Austrian, or Swiss population were considered. Second, articles comparing test performances of healthy controls vs. Parkinson's disease and/or different cognitive Parkinson's disease subtypes (e.g. no cognitive impairment, Parkinson's with mild cognitive impairment, Parkinson's disease dementia) were selected. Effect sizes for group differentiation were calculated. RESULTS: Out of 127 full-text articles reviewed, 48 tests were identified during the first literature search. In the second search, 1716 articles were reviewed and 23 papers selected. The strongest effect sizes for group discrimination were revealed for tests assessing executive function, attention, and visuo-cognitive abilities. Based on the results of the two literature searches, consensus guidelines were defined by the authors, allowing for Level-II diagnosis for Parkinson's with mild cognitive impairment and Parkinson's disease dementia. CONCLUSIONS: The presented guidelines may have the potential to standardize and improve the neuropsychological assessment of Parkinson's disease patients in German speaking countries.

Awareness of genetic risk in the Dominantly Inherited Alzheimer Network (DIAN).

INTRODUCTION: Although some members of families with autosomal dominant Alzheimer's disease mutations learn their mutation status, most do not. How knowledge of mutation status affects clinical disease progression is unknown. This study quantifies the influence of mutation awareness on clinical symptoms, cognition, and biomarkers. METHODS: Mutation carriers and non-carriers from the Dominantly Inherited Alzheimer Network (DIAN) were stratified based on knowledge of mutation status. Rates of change on standard clinical, cognitive, and neuroimaging outcomes were examined. RESULTS: Mutation knowledge had no associations with cognitive decline, clinical progression, amyloid deposition, hippocampal volume, or depression in either carriers or non-carriers. Carriers who learned their status mid-study had slightly higher levels of depression and lower cognitive scores. DISCUSSION: Knowledge of mutation status does not affect rates of change on any measured outcome. Learning of status mid-study may confer short-term changes in cognitive functioning, or changes in cognition may influence the determination of mutation status.

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.

Relationship between physical activity, cognition, and Alzheimer pathology in autosomal dominant Alzheimer's disease.

INTRODUCTION: Little is known about effects of physical activity (PA) in genetically driven early-onset autosomal dominant Alzheimer's disease (AD). METHODS: A total of 372 individuals participating at the Dominantly Inherited Alzheimer Network study were examined to evaluate the cross-sectional relationship of PA with cognitive performance, functional status, cognitive decline, and AD biomarkers in cerebrospinal fluid. Mutation carriers were categorized as high or low exercisers according to WHO recommendations. RESULTS: Mutation carriers with high PA showed significantly better cognitive and functional performance and significantly less AD-like pathology in cerebrospinal fluid than individuals with low PA. Mutation carriers with high PA scored 3.4 points better on Mini Mental State Examination at expected symptom onset and fulfilled the diagnosis of very mild dementia 15.1 years later compared with low exercisers. DISCUSSION: These results support a beneficial effect of PA on cognition and AD pathology even in individuals with genetically driven autosomal dominant AD.

Home-Based Physical Behavior in Late Stage Parkinson Disease Dementia: Differences between Cognitive Subtypes.

BACKGROUND: For the early diagnosis of Parkinson disease dementia (PDD), objective home-based tools are needed to quantify even mild stages of dysfunction of the activities of daily living (ADL). OBJECTIVES: In this pilot study, home-based physical behavior was assessed to examine whether it is possible to distinguish mild cognitive impairment (PD-MCI) from PDD. METHODS: Fifty-five patients with mild to severe Parkinson disease (PD) participated in this cross-sectional study. Based on comprehensive neuropsychological testing, PD patients were classified as cognitively nonimpaired (PD-NC), PD-MCI or PDD. For physical behavior assessments, patients wore the accelerometer DynaPort® (McRoberts) for 3 days. Ordinal logistic regression models with continuous Y were applied to correct results for motor impairment and depressive symptoms. RESULTS: After excluding 7 patients due to insufficient wearing time, 48 patients with a mean of 2 recorded days were analyzed (17 PD-NC, 22 PD-MCI, 9 PDD). ADL-impaired PDD patients showed fewer sedentary bouts than non-ADL-impaired PD-MCI (p = 0.01, odds ratio [OR] = 8.9, 95% confidence interval [CI] = 1.8-45.2) and PD-NC (p = 0.01, OR = 10.3, CI = 1.6-67.3) patients, as well as a longer sedentary bout length (PD-NC: p = 0.02, OR = 0.1, CI = 0.02-0.65; PD-MCI: p = 0.02, OR = 0.14, CI = 0.03-0.69). These differences were mainly caused by fewer (PD-NC: p = 0.02, OR = 9.6, CI = 1.5-62.4; PD-MCI: p = 0.01, OR = 8.5, CI = 1.5-37.3) but longer sitting bouts (PD-NC: p = 0.03, OR = 0.12, CI = 0.02-0.80; PD-MCI: p = 0.04, OR = 0.19, CI = 0.04-0.93). Tests assessing executive function, visuoconstruction and attention correlated significantly with specific activity parameters (ρ ≥ 0.3; p < 0.05). CONCLUSION: Objective assessment of physical behavior, in particular the detection of sedentary bouts, is a promising contributor to the discrimination between PD-MCI and PDD.

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 Parkinson's 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 Parkinson's 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.

Avoid or Embrace? Practice Effects in Alzheimer's Disease Prevention Trials.

Demonstrating a slowing in the rate of cognitive decline is a common outcome measure in clinical trials in Alzheimer's disease (AD). Selection of cognitive endpoints typically includes modeling candidate outcome measures in the many, richly phenotyped observational cohort studies available. An important part of choosing cognitive endpoints is a consideration of improvements in performance due to repeated cognitive testing (termed "practice effects"). As primary and secondary AD prevention trials are comprised predominantly of cognitively unimpaired participants, practice effects may be substantial and may have considerable impact on detecting cognitive change. The extent to which practice effects in AD prevention trials are similar to those from observational studies and how these potential differences impact trials is unknown. In the current study, we analyzed data from the recently completed DIAN-TU-001 clinical trial (TU) and the associated DIAN-Observational (OBS) study. Results indicated that asymptomatic mutation carriers in the TU exhibited persistent practice effects on several key outcomes spanning the entire trial duration. Critically, these practice related improvements were larger on certain tests in the TU relative to matched participants from the OBS study. Our results suggest that the magnitude of practice effects may not be captured by modeling potential endpoints in observational studies where assessments are typically less frequent and drug expectancy effects are absent. Using alternate instrument forms (represented in our study by computerized tasks) may partly mitigate practice effects in clinical trials but incorporating practice effects as outcomes may also be viable. Thus, investigators must carefully consider practice effects (either by minimizing them or modeling them directly) when designing cognitive endpoint AD prevention trials by utilizing trial data with similar assessment frequencies.

Long-Term Cognitive Decline Related to the Motor Phenotype in Parkinson's Disease.

BACKGROUND: Parkinson's disease (PD) is associated with various non-motor symptoms, including cognitive deterioration. OBJECTIVE: Here, we used data from the DEMPARK/LANDSCAPE cohort to describe the association between progression of cognitive profiles and the PD motor phenotypes: postural instability and gait disorder (PIGD), tremor-dominant (TR-D), and not-determined (ND). METHODS: Demographic, clinical, and neuropsychological six-year longitudinal data of 711 PD-patients were included (age: M = 67.57; 67.4% males). We computed z-transformed composite scores for a priori defined cognitive domains. Analyses were controlled for age, gender, education, and disease duration. To minimize missing data and drop-outs, three-year follow-up data of 442 PD-patients was assessed with regard to the specific role of motor phenotype on cognitive decline using linear mixed modelling (age: M = 66.10; 68.6% males). RESULTS: Our study showed that in the course of the disease motor symptoms increased while MMSE and PANDA remained stable in all subgroups. After three-year follow-up, significant decline of overall cognitive performance for PIGD-patients were present and we found differences for motor phenotypes in attention (ß= -0.08, SE = 0.003, p < 0.006) and memory functions showing that PIGD-patients deteriorate per months by -0.006 compared to the ND-group (SE = 0.003, p = 0.046). Furthermore, PIGD-patients experienced more often difficulties in daily living. CONCLUSION: Over a period of three years, we identified distinct neuropsychological progression patterns with respect to different PD motor phenotypes, with early executive deficits yielding to a more amnestic profile in the later course. Here, in particular PIGD-patients worsened over time compared to TR-D and ND-patients, highlighting the greater risk of dementia for this motor phenotype.

Cognitive impairment and sedentary behavior predict health-related attrition in a prospective longitudinal Parkinson's disease study.

INTRODUCTION: In Parkinson's disease (PD), the high burden of motor and non-motor symptoms, such as cognitive impairment or falls, is associated with rapid disease progression and mortality. This is often reflected by an increased drop-out rate of PD patients in longitudinal studies. Active physical behavior can impact the disease course beneficially and has an overall positive effect on health. Contrarily, sedentary behavior is associated with cognitive impairment in PD. The aim of this study was to investigate whether sedentary physical behavior assessed in the home environment and cognitive impairment can predict health-related study attrition due to sickness and death in PD. METHODS: Data of 45 PD patients, longitudinally assessed, were analyzed. Of those, 20 patients completed six yearly visits, 16 dropped out due to sickness or death, and nine for other reasons. All patients wore a mobile device to assess physical behavior and completed cognitive testing. RESULTS: Logistic regression revealed global cognition was the primary predictor for health-related drop-out in varying models (p ≤ .04). In the survival analysis, cognitive impairment (p = .005) and longer sedentary mean bout length (p = .02) were associated with drop-out due to sickness and death. The occurrence of health-related study drop-out or death was highest in patients with both impaired cognition and longer sedentary bouts. CONCLUSIONS: Cognition was the primary predictor for study drop-out due to sickness and death. However, it seems that sedentary behavior might have a potential negative influence on PD patients' health, especially those with cognitive impairment.

Relationships between big-five personality factors and Alzheimer's disease pathology in autosomal dominant Alzheimer's disease.

INTRODUCTION: Changes in personality characteristics are associated with the onset of symptoms in Alzheimer's disease (AD) and may even precede clinical diagnosis. However, personality changes caused by disease progression can be difficult to separate from changes that occur with normal aging. The Dominantly Inherited Alzheimer Network (DIAN) provides a unique cohort in which to relate measures of personality traits to in vivo markers of disease in a much younger sample than in typical late onset AD. METHODS: Personality traits measured with the International Personality Item Pool at baseline from DIAN participants were analyzed as a function of estimated years to onset of clinical symptoms and well-established AD biomarkers. RESULTS: Both neuroticism and conscientiousness were correlated with years to symptom onset and markers of tau pathology in the cerebrospinal fluid. Self-reported conscientiousness and both neuroticism and conscientiousness ratings from a collateral source were correlated with longitudinal rates of cognitive decline such that participants who were rated as higher on neuroticism and lower on conscientiousness exhibited accelerated rates of cognitive decline. DISCUSSION: Personality traits are correlated with the accumulation of AD pathology and time to symptom onset, suggesting that AD progression can influence an individual's personality characteristics. Together these findings suggest that measuring neuroticism and conscientiousness may hold utility in tracking disease progression in AD.

Serum neurofilament dynamics predicts neurodegeneration and clinical progression in presymptomatic Alzheimer's disease.

Neurofilament light chain (NfL) is a promising fluid biomarker of disease progression for various cerebral proteopathies. Here we leverage the unique characteristics of the Dominantly Inherited Alzheimer Network and ultrasensitive immunoassay technology to demonstrate that NfL levels in the cerebrospinal fluid (n = 187) and serum (n = 405) are correlated with one another and are elevated at the presymptomatic stages of familial Alzheimer's disease. Longitudinal, within-person analysis of serum NfL dynamics (n = 196) confirmed this elevation and further revealed that the rate of change of serum NfL could discriminate mutation carriers from non-mutation carriers almost a decade earlier than cross-sectional absolute NfL levels (that is, 16.2 versus 6.8 years before the estimated symptom onset). Serum NfL rate of change peaked in participants converting from the presymptomatic to the symptomatic stage and was associated with cortical thinning assessed by magnetic resonance imaging, but less so with amyloid-ß deposition or glucose metabolism (assessed by positron emission tomography). Serum NfL was predictive for both the rate of cortical thinning and cognitive changes assessed by the Mini-Mental State Examination and Logical Memory test. Thus, NfL dynamics in serum predict disease progression and brain neurodegeneration at the early presymptomatic stages of familial Alzheimer's disease, which supports its potential utility as a clinically useful biomarker.

The Multiple Object Test as a performance-based tool to assess the decline of ADL function in Parkinson's disease.

INTRODUCTION: As cognitive-driven worsening of activities of the daily living (ADL) in Parkinson's disease (PD) is the core feature of PD dementia (PDD), there is great need for sensitive quantitative assessment. Aim of our study was the evaluation of cognitive-driven worsening of ADL by the performance-based Multiple Object Test (MOT), offering an essential clinical advantage as it is quick and easy to apply in a clinical context even on severely impaired patients. METHODS: 73 PD patients were assessed longitudinally over a period of 37 (6-49) months. According to their neuropsychological profile the sample was divided into two groups: PD patients with (n = 34, PD-CI) and without cognitive impairment (n = 39, PD-noCI). The MOT comprises five routine tasks (e.g. to make coffee) quick and easy to apply. Quantitative (total error number, processing time) and qualitative parameters (error type) were analyzed using non-parametric test statistic (e.g.Wilcoxon signed-rank test, binary logistic regression). RESULTS: Median number of total errors (p = 0.001), processing time (p<0.001), perplexity (p = 0.035), and omission errors (p<0.001) increased significantly from baseline to follow-up in the total sample. Worsening of MOT performance was correlated to cognitive decline in the attention/ executive function and visuo-constructive domain. PD-CI showed an increase in omission errors (p = 0.027) compared to PD-noCI over time. This increase in omission errors between visits was further identified as a risk marker for PDD conversion. CONCLUSION: The MOT, especially frequency of omission errors, is a promising tool to rate PD patients objectively and might help to identify patients with a high risk for having mild cognitive impairment or dementia.

The association between objectively measured physical activity, depression, cognition, and health-related quality of life in Parkinson's disease.

BACKGROUND: Lower levels of physical activity are associated with lower Health-Related Quality of Life (HRQoL) in Parkinson's disease (PD). We evaluated the influence of quantitative physical activity parameters among other (disease-related) features representing other domains of the WHO International model for classification of Function, Disability, and Health (ICF) on HRQoL in PD. METHODS: Home-based movement data (DynaPort MiniMod®) was collected in 47 PD patients. Nine stepwise regression models were calculated, with consecutive outcome variables: Parkinson's Disease Questionnaire (PDQ) Summary Index (SI), PDQ-Mobility, PDQ-Activities of Daily Living (ADL). Demographic variables, disease-specific features, and quantitative physical activity parameters, were included as predicting variables in all analyses. The following three physical activity parameters were alternately included for both sedentary and active episodes: 'percentage' of 24 h spent within these episodes, 'number of bouts', and 'mean bout lengths' (MBL). RESULTS: Depression and 'Total Energy Expenditure' were the main predictors of overall HRQoL (PDQ-SI), independent of the permutation of activity parameters. The same parameters predicted the PDQ-Mobility score. However, this result was altered when 'MBL' parameters were included into the model, 'MBL' of sedentary episodes additionally predicted HRQoL-Mobility. The PDQ-ADL score was associated with demographic, motor, and non-motor variables including cognitive status. After exclusion of demented PD patients, older age and cognitive impairment no longer constrained HRQoL-ADL. DISCUSSION: For the first time, we showed the influence of objective, home-based measured physical activity among depression and cognition on HRQoL in PD. This suggests that a multifactorial treatment approach would be most successful to increase HRQoL in PD.

Decreased body mass index in the preclinical stage of autosomal dominant Alzheimer's disease.

The relationship between body-mass index (BMI) and Alzheimer´s disease (AD) has been extensively investigated. However, BMI alterations in preclinical individuals with autosomal dominant AD (ADAD) have not yet been investigated. We analyzed cross-sectional data from 230 asymptomatic members of families with ADAD participating in the Dominantly Inherited Alzheimer Network (DIAN) study including 120 preclinical mutation carriers (MCs) and 110 asymptomatic non-carriers (NCs). Differences in BMI and their relation with cerebral amyloid load and episodic memory as a function of estimated years to symptom onset (EYO) were analyzed. Preclinical MCs showed significantly lower BMIs compared to NCs, starting 11.2 years before expected symptom onset. However, the BMI curves begun to diverge already at 17.8 years before expected symptom onset. Lower BMI in preclinical MCs was significantly associated with less years before estimated symptom onset, higher global Aß brain burden, and with lower delayed total recall scores in the logical memory test. The study provides cross-sectional evidence that weight loss starts one to two decades before expected symptom onset of ADAD. Our findings point toward a link between the pathophysiology of ADAD and disturbance of weight control mechanisms. Longitudinal follow-up studies are warranted to investigate BMI changes over time.

The Multiple Object Test as a Performance Based Tool to Assess Cognitive Driven Activity of Daily Living Function in Parkinson's Disease.

BACKGROUND: There is need for multidimensional quantitative assessment of cognitive driven activities of daily living (ADL) functions in Parkinson's disease (PD). OBJECTIVE: To determine whether there is an ADL profile related to cognitive impairment in PD assessed by the Multiple Object Test (MOT). We assumed MOT performance to be lower in PD patients versus controls and in PD patients with more severe cognitive impairment. METHODS: 50 PD patients with no cognitive impairment (PD-NC), 54 patients with PD-mild cognitive impairment (PD-MCI), 29 with Parkinson's disease dementia (PDD), and 40 healthy controls (HC) were investigated. Besides comprehensive cognitive testing, the MOT, a performance based test consisting of five routine tasks (e.g., preparing a cup of coffee), was applied. Quantitative (total errors and time) and qualitative (error type) MOT parameters were analyzed. RESULTS: Total time and number of MOT errors was increased in PD patients compared to controls (p < 0.001). These parameters also differentiated PDD patients from other cognitive groups (p < 0.05). No control subject had ≥ 4 errors in the MOT, but 30% of PD patients, especially PDD, scored above this cut-off. Omission (p < 0.001) and mislocation (p < 0.03) errors were more prominent in PDD than other cognitive groups. Perplexity errors did not differ between PD-MCI and PDD but between PD-NC and PDD (p = 0.01). MOT parameters discriminating between cognitive groups correlated mainly with lower test performance in psychomotor speed and executive function. CONCLUSION: Performance based testing is promising to identify quantitative and qualitative ADL aspects differentiating between different cognitive groups which might be helpful for an early detection of PDD.

Cognitive Performance Patterns in Healthy Individuals with Substantia Nigra Hyperechogenicity and Early Parkinson's Disease.

Introduction: Hyperechogenicity of the substantia nigra (SN+) is a risk marker for Parkinson's disease (PD) which can be detected before the diagnosis. In healthy individuals, SN+ has been associated with slight deficits in specific cognitive functions, suggesting cognitive impairment as a possible pre-diagnostic marker for PD. However, the pattern of cognitive deficits associated with SN+ has not yet been compared with those present in PD. Methods: Data of 262 healthy individuals with normal echogenicity (SN-) and 48 healthy individuals with SN+ were compared with 82 early stage PD patients using the "Consortium to Establish a Registry for Alzheimer's disease" test battery. First, the test clusters (factors) were identified using a principal component analysis (PCA). Mean group performance of cognitive tests belonging to distinct factors, according to the PCA, and single subtest performances were compared using analyses of variance. Second, the number of individuals with abnormal cognitive performances (z-score < -1.0) were compared between groups. Results: Verbal memory, semantic and executive function, and praxis were identified as components of cognitive performances. The SN+ group performed significantly worse than the SN- group in tests assessing semantic and executive function, with a non-significant decrease in verbal memory. On the subtest level, individuals of the SN+ group scored significantly lower than the SN- group on the Boston Naming Test (BNT; p = 0.008). In all subtests, the percentages of PD patients with values below the cut-off for abnormal performance were higher than in the SN- group. Moreover, more individuals from the SN+ group scored below the cut-off in the BNT (SN- = 8.4%, SN+ = 20.8%, p = 0.01) and TMT-B (SN- = 6.9%, SN+ = 16.7%, p = 0.02), compared to the SN- group. Conclusion: This study confirms poorer performance of healthy individuals with SN+ compared to SN- in specific cognitive domains. However, against the SN- group, the cognitive profile of the SN+ group was not fully consistent with the profile of early PD patients. Our data argues that cognitive impairment associated with SN+ might differ slightly from that seen in early PD. Compensational mechanisms in the early phases of neurodegeneration, and the fact that only a subgroup of SN+ will develop PD, may partly explain these differences.

Apolipoprotein E ε4 does not affect cognitive performance in patients with Parkinson's disease.

INTRODUCTION: Cognitive impairment is a common and disabling non-motor symptom in Parkinson's disease (PD). The apolipoprotein E (APOE) allele ε4 is a known risk factor for Alzheimer's disease and has also been suggested to be a risk factor for dementia in PD and even a predictor of impairment in certain cognitive domains. METHODS: A total of 447 PD patients (PD patients without cognitive impairment: n = 187; PD patients with mild cognitive impairment: n = 188; PD patients with dementia: n = 72) were included from an ongoing observational German multicenter cohort study (LANDSCAPE study). All patients underwent an extensive neuropsychological test battery, including assessments of memory, visuospatial functioning, attention, language, and executive function. APOE genotype was determined by an allelic discrimination assay. Linear regression analysis was used to explore the associations between APOE-ε4 and cognitive performance. RESULTS: The APOE-ε4 allele was not associated with a diagnosis of cognitive impairment in PD (PD with mild cognitive impairment and PD with dementia) or with deficits in specific neuropsychological domains in our study cohort. CONCLUSION: Our data question the relevance of the APOE-ε4 allele as a predictor of cognitive impairment in PD.

Diagnostic Value of Subjective Memory Complaints Assessed with a Single Item in Dominantly Inherited Alzheimer's Disease: Results of the DIAN Study.

OBJECTIVE: We examined the diagnostic value of subjective memory complaints (SMCs) assessed with a single item in a large cross-sectional cohort consisting of families with autosomal dominant Alzheimer's disease (ADAD) participating in the Dominantly Inherited Alzheimer Network (DIAN). METHODS: The baseline sample of 183 mutation carriers (MCs) and 117 noncarriers (NCs) was divided according to Clinical Dementia Rating (CDR) scale into preclinical (CDR 0; MCs: n = 107; NCs: n = 109), early symptomatic (CDR 0.5; MCs: n = 48; NCs: n = 8), and dementia stage (CDR ≥ 1; MCs: n = 28; NCs: n = 0). These groups were subdivided by the presence or absence of SMCs. RESULTS: At CDR 0, SMCs were present in 12.1% of MCs and 9.2% of NCs (P = 0.6). At CDR 0.5, SMCs were present in 66.7% of MCs and 62.5% of NCs (P = 1.0). At CDR ≥ 1, SMCs were present in 96.4% of MCs. SMCs in MCs were significantly associated with CDR, logical memory scores, Geriatric Depression Scale, education, and estimated years to onset. CONCLUSIONS: The present study shows that SMCs assessed by a single-item scale have no diagnostic value to identify preclinical ADAD in asymptomatic individuals. These results demonstrate the need of further improvement of SMC measures that should be examined in large clinical trials.

Speech perception deficits in Parkinson's disease: underestimation of time intervals compromises identification of durational phonetic contrasts.

Besides motor, vegetative, and cognitive signs, patients suffering from Parkinson's disease (PD) may show distinct perceptual deficits such as underestimation of time intervals extending across several seconds. Assuming this impairment also to affect the domain of tens of milliseconds, disrupted encoding of the acoustic speech signal with respect to segment durations conveying linguistic information must be expected. To test this hypothesis, 10 PD patients and matched controls performed an identification task using a series of 10 stimuli derived from the utterance "Boten" (/bo:tn/, 'messengers'; produced with nasal plosion) by exclusive manipulation of occlusion length (110-20 ms in steps of 10 ms). Under these conditions, word-medial silence cues the voicing category of the respective stop consonant. Seven PD subjects showed normal identification curves, i.e., categorized the shortest and longest stimuli with high probability each as the minimal pair cognates "Boden" and "Boten," respectively. In contrast, the remaining three patients labeled all items across the complete range of occlusion lengths as "Boden." A subsequent experiment found a horizontal shift of the identification curves toward larger signal durations (> 120 ms) in these three subjects. Bilateral cerebellar degeneration has been found to yield a different response pattern, i.e., near-chance level of performance. Considering recent information-processing models of scalar interval timing, striatal disorders seem to slow down an oscillatory pacemaker, whereas cerebellar dysfunctions may impair comparison of measured durations with stored reference memory traces.