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Introduction The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) is a renowned cognitive test battery, which has been extended in its German version to the CERAD-Plus including tests of executive functions and processing speed. The most commonly used total score (TS) is based on the restricted CERAD version and reflects the sum of selected raw-values (Chandler et al., 2005). The CERAD-Plus extensions might be of particular diagnostic utility for cognitive assessments in Parkinson's Disease (PD), as executive functions and processing speed belong to the most vulnerable domains in PD. Objective The aim was to develop a CERAD-TS based on the extended CERAD-Plus' age-, gender-, and education-corrected z-scores and to evaluate its diagnostic accuracy compared to the established CERAD-Chandler-TS. Methods Baseline data of n = 679 patients with PD (69% male, n = 277 PD without cognitive impairment, n = 307 PD-MCI, n = 95 PD-D) from the multicenter, prospective DEMPARK/LANDSCAPE study were analyzed. ROC-analyses were conducted for four different TS that were either based on the original CERAD or CERAD-Plus, on raw-values or z-scores, and equally-weighted or based on factor scores. AUC-comparisons were conducted to determine the best yet most parsimonious TS. Results The newly designed CERAD-Plus-TS based on equally-weighted z-scores outperformed both the CERAD-Chandler-TS and cognitive screening instruments when differentiating between individuals with PD of varying cognitive impairment (0.78 ≤ AUC ≤ 0.98). Conclusion Results suggest a high relevance of non-amnestic subscales for the cognitive assessment in PD populations. The proposed CERAD-Plus-TS needs further validation. The extensions might offer diagnostic potential for non-PD populations as well.

Background: Depressive symptoms often co-occur with Alzheimer’s disease (AD) and can impact neuropsychological test results. In early stages of AD, disentangling cognitive impairments due to depression from those due to neurodegeneration often poses a challenge. Objective: We aimed to identify neuropsychological tests able to detect AD-typical pathology while taking into account varying degrees of depressive symptoms. Methods: A battery of neuropsychological tests (CERAD-NP) and the Geriatric Depression Scale (GDS) were assessed, and cerebrospinal fluid (CSF) biomarkers were obtained. After stratifying patients into CSF positive or negative and into low, moderate, or high GDS score groups, sensitivity and specificity and area under the curve (AUC) were calculated for each subtest. Results: 497 participants were included in the analyses. In patients with low GDS scores (≤10), the highest AUC (0.72) was achieved by Mini-Mental State Examination, followed by Constructional Praxis Recall and Wordlist Total Recall (AUC = 0.714, both). In patients with moderate (11–20) and high (≥21) GDS scores, Trail Making Test-B (TMT-B) revealed the highest AUCs with 0.77 and 0.82, respectively. Conclusion: Neuropsychological tests showing AD-typical pathology in participants with low GDS scores are in-line with previous results. In patients with higher GDS scores, TMT-B showed the best discrimination. This indicates the need to focus on executive function rather than on memory task results in depressed patients to explore a risk for AD.

Introduction: Harmonized neuropsychological assessment for neurocognitive disorders, an international priority for valid and reliable diagnostic procedures, has been achieved only in specific countries or research contexts.Methods: To harmonize the assessment of mild cognitive impairment in Europe, a workshop (Geneva, May 2018) convened stakeholders, methodologists, academic, and non-academic clinicians and experts from European, US, and Australian harmonization initiatives.Results: With formal presentations and thematic working-groups we defined a standard battery consistent with the U.S. Uniform DataSet, version 3, and homogeneous methodology to obtain consistent normative data across tests and languages. Adaptations consist of including two tests specific to typical Alzheimer's disease and behavioral variant frontotemporal dementia. The methodology for harmonized normative data includes consensus definition of cognitively normal controls, classification of confounding factors (age, sex, and education), and calculation of minimum sample sizes.Discussion: This expert consensus allows harmonizing the diagnosis of neurocognitive disorders across European countries and possibly beyond.

Objectives:Parkinson’s disease (PD) patients with mild cognitive impairment (PD-MCI) have an increased risk of developing dementia (PDD). As activities of daily living (ADL) impairment is mandatory for the diagnosis of PDD, assessing early signs of instrumental ADL (iADL) dysfunction, especially in PD-MCI, is essential. In PD, self- and caregiver-reported iADL performance is often confounded by motor dysfunction and mood. Objective and time-efficient performance-based measurements are needed to screen for cognitive-related iADL dysfunction. We evaluated the Erlangen Test of Activities of Daily Living in Mild Dementia and Mild Cognitive Impairment (ETAM) in PD and determined its value for characterizing a subgroup of PD-MCI patients with mild performance-based iADL impairment.Methods:Twenty-one cognitively normal PD patients (PD-NC), 24 PD-MCI patients, and 18 healthy controls (HC) were analyzed. Assessments included the ETAM, a comprehensive neuropsychological test battery, iADL, mood, and motor measurements.Results:PD-MCI patients scored significantly lower on the ETAM total score compared to PD-NC patients (p = .002), whereas HC and PD-NC patients did not statistically differ. No HC scored lower than 27 points (diagnostic cutoff for mild iADL impairment); only PD-MCI patients scored below this cutoff (29.2%) suggesting the ETAM is able to characterize a PD-MCI subgroup with early iADL impairment. PD-MCI patients below the cutoff were more impaired in the attention domain (p = .04).Conclusions:The ETAM is a potentially valuable clinical assessment, able to detect first signs of iADL dysfunction in PD-MCI. Further studies in larger cohorts are needed to evaluate the prognostic ability for predicting PDD.

Background Visual neglect and extinction are two common neurological syndromes in patients with right-hemispheric brain damage. Whether and how these two syndromes are associated or share common neural substrates is still a matter of debate. Methods To address these issues, the authors investigated 56 patients with right-hemispheric stroke with a novel diagnostic test to detect extinction and neglect. In this computerised task, subjects had to respond to target stimuli in uni- and bilateral stimulation conditions with detection probabilities being assessed. A cluster-analytical approach identified 18 patients with neglect and 13 patients with extinction. Statistical lesion-symptom mapping analyses with measures for extinction and neglect were performed. Results Extinction and neglect co-occurred in a subset of patients but were also observed independently from each other, thereby constituting a double dissociation. Lesions within the right inferior parietal cortex were significantly associated with the severity of visual extinction. Visuospatial neglect was related to damage of fronto-parietal brain regions, with parieto-occipital areas affecting line bisection and dorsal fronto-parietal areas affecting cancellation task performance, respectively. Conclusion Quantifying lesion-induced symptoms with this novel paradigm shows that extinction and neglect are dissociable syndromes in patients with right-hemispheric stroke. Furthermore, extinction and neglect can be related to differential neural substrates, with extinction being related to focal brain damage within the right inferior parietal cortex.

The mini-mental status examination (MMSE) includes a task in which participants are asked to write a sentence of their own choice. The emotional tone of the sentence may be related to the emotions of the writer; therefore, it was investigated whether the emotional tone of the sentence in the MMSE written by people with dementia was associated with health-related quality of life and depressive symptoms.A secondary analysis was carried out based on the cross-sectional data of 107 people with dementia included in the '7th framework EU project RightTimePlaceCare'. Two raters assessed the emotional tone of the sentence based on a standardized procedure as positive, neutral or negative. The association between the emotional tone of the sentence, health-related quality of life and depressive symptoms was investigated. Health-related quality of life was assessed by the quality of life in Alzheimer's disease questionnaire and depressive symptoms by the Cornell scale for depression in dementia questionnaire.The sentences were rated as either positive or neutral in both cases with 42 % and 16 % were judged to have a negative emotional tone. The variance analysis by ANOVA indicated significant differences between the three groups of sentences regarding health-related quality of life of the writer (p = 0.04). The results of the Scheffé test confirmed a significant difference between sentences with a positive and negative tone and the health-related quality of life where people who wrote a sentence with a negative tone showed a lower health-related quality of life (p = 0.043). No significant association was revealed regarding depressive symptoms (p = 0.97).It remains to be investigated in future studies whether the emotional tone is a reliable indicator of health-related quality of life and depressive symptoms of people with dementia, so that the written MMSE sentence can be used for diagnostic purposes.

Objective: This study tested the hypothesis that patients with primary progressive aphasia (PPA) who do not meet the proposed criteria for any of the recognized subtypes would have the atrophy pattern reported in the past for logopenic variant PPA (lvPPA), in turn suggesting that the PPA of likely Alzheimer disease origin is more variable than that captured in the current lvPPA diagnostic recommendations. Methods: MRI gray matter volumes from 14 patients with mixed PPA who failed to meet the diagnostic recommendations for any recognized variant were compared with those of 25 matched control participants via voxel-based morphometry. Results: The mixed PPA group had left temporoparietal atrophy with a pattern identical to that in previously reported lvPPA cohorts. Conclusion: Patients with PPA who did not meet the criteria for any recognized PPA variant at their initial assessment had the group-level atrophy pattern previously reported as the hallmark of lvPPA. We suggest that the specific language features proposed for lvPPA are too narrow to characterize the language impairments arising from likely Alzheimer pathology.

Objectives To establish the diagnostic accuracy of the Total Score of the Consortium to Establish a Registry for Alzheimer's Disease neuropsychological assessment battery (CERAD-NP) both for cross-sectional discrimination of Alzheimer disease (AD) dementia and short-term prediction of incident AD dementia. Design Longitudinal cohort study with two assessments at a 1.5-year interval. Setting Primary care sample randomly recruited via medical record registries. Participants As part of the German Study on Ageing, Cognition, and Dementia (AgeCoDe), a sample of elderly individuals (N = 1,606; mean age: 84 years) was assessed. Measurements Subjects were assessed with the CERAD-NP and followed up for 18 months (97.6% follow-up rate). Logistic regression and receiver-operating-characteristic (ROC) curve analysis were used to compare the diagnostic accuracy of the CERAD-NP Total Score (CTS) with that of single CERAD-NP scores and the Mini-Mental-State-Examination (MMSE) score. Results ROC curve analysis resulted in excellent (area under the curve [AUC]: 0.97) cross-sectional discrimination between non-AD and AD dementia subjects. Prediction of incident AD dementia with the CTS was also very good (AUC: 0.89), and was significantly better than prediction based on the MMSE. Conclusions The cross-sectional results confirm that the CTS is a highly accurate diagnostic tool for detecting AD dementia in elderly primary care patients. In addition, we provide evidence that the CTS is also accurate for the prediction of incident AD dementia. These findings further support the validity of the CTS as an index of overall cognitive functioning for detection and prediction of AD dementia.

The investigation of cerebral resting-state networks (RSNs) by functional magnetic resonance imaging (fMRI) is a promising tool for the early diagnosis and follow-up of neuropsychiatric and neurodegenerative disorders like Alzheimer's disease (AD). In this context, the determination of inter-session reliability of these networks is crucial. However, data on network reliability in healthy elderly subjects is rare and does not exist for patients with amnestic mild cognitive impairment (aMCI), a prodromal stage of AD. Therefore, the aim of this study was to investigate the long-term test-retest reliability of RSNs in both groups. Twelve healthy controls (HC) and 13 aMCI patients underwent resting-state fMRI and neuropsychological testing (CERAD test battery) twice, at baseline and after 13-16 months. Resting-state fMRI data was decomposed into independent components using independent component analysis. Inter-session test-retest reliability of the resulting RSNs was determined by calculating voxel-wise intra-class correlation coefficients. Overall test-retest reliability of corresponding RSNs was moderate to high in both groups, but significantly higher in the HC group compared to the aMCI group (p0.001), while the cognitive performance within the CERAD test battery remained stable over time in either group. Most reliable RSNs derived from the HC group and were associated with sensory and motor as well as higher order cognitive and the default-mode function. Particularly low reliability was found in basal frontal regions, which are known to be prone to susceptibility-induced noise. We conclude that stable RSNs may represent healthy aging, whereas decreased RSN reliability may indicate progressive neuro-functional alterations before the actual manifestation of clinical symptoms.