A Comparison of Serial Position Effects in Patients with Mild Cognitive Impairment due to Parkinson's Disease or to Alzheimer's Disease.

OBJECTIVE: The first (primacy region) and last (recency region) items of a word list are generally better memorized than items from the middle region. The recency effect depends on short-term memory (STM) and the primacy effect on long-term memory (LTM), where verbal information is transferred from STM into LTM by maintenance rehearsal. We compared the serial position effects (SPE) between patients with mild cognitive impairment (MCI) due to Parkinson's disease (PD), i.e., PD-MCI, and patients with MCI due to Alzheimer's disease (AD-MCI), and evaluated the influence of SPE and frontostriatal deficits on verbal memory recall. METHODS: Four similar groups of subjects participated in the study: 26 PD-MCI patients, 26 cognitively normal patients with PD (PD-CN), 26 AD-MCI patients, and 26 normal controls (NC). Verbal episodic memory, verbal span, attentional capacity, executive functions, and verbal working memory performance were assessed. Measures for primacy and recency regions were defined at the first trial of a 16-items word list. Hierarchical regression models were used to investigate the contribution of frontostriatal deficits beyond SPE on verbal memory recall performance ("long-delay free recall") in PD and AD patients. RESULTS: Primacy effects were significantly diminished in both PD-MCI and AD-MCI patients relative to NC and PD-CN (all p < 0.01). Compared to PD-MCI patients, AD-MCI patients exhibited significantly worse "delayed-recall 'savings'." Reduced primacy effect was predictive for decreased recall performance in PD and AD. The conducted hierarchical regression model revealed that in PD, but not in AD patients, performance of attention and executive function significantly increased the prediction of free recalled words. CONCLUSIONS: Reduced recall performance is likely due to impaired transition of newly learned material from STM into LTM in AD and in PD. Whereas AD-MCI patients suffer from a storage deficit, the similarly reduced recall performance found in patients with PD-MCI may additionally be related to deficient attentional and executive capacity.

Development of a Novel Self-administered Cognitive Assessment Tool and Normative Data for Older Adults.

BACKGROUND: Preexisting cognitive impairment in surgical patients is one of the leading risk factors for adverse cognitive outcomes such as postoperative delirium and postoperative cognitive dysfunction. We developed a self-administered tablet computer application intended to assess the individual risk for adverse postoperative cognitive outcomes. This cross-sectional study aimed to establish normative data for the tool. MATERIALS AND METHODS: Healthy volunteers aged 65 years and above were administered the Mini-Mental State Examination, Geriatric Depression Scale, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery to assess cognitive health. All subjects completed the tablet computer application without assistance. Primary outcome measure was the test performance. Regression models were built for each cognitive domain score with the covariates age, sex, and education in cognitively healthy subjects. Demographically adjusted standard scores (z-scores) were computed for each subtest. RESULTS: A total of 283 participants (155 women, 128 men) were included in the final analysis. Participants' age was 73.8±5.2 years (mean±SD) and their level of education was 13.6±2.9 years. Mini-Mental State Examination score was 29.2±0.9 points, Geriatric Depression Scale score was 0.4±0.7 points, and Consortium to Establish a Registry for Alzheimer's Disease-Neuropsychological Assessment Battery total score was 98.7±5.7 points. Older age was associated with poorer performance in the visual recognition task and in Trail Making Test B (P<0.05 after Bonferroni-Holm adjustments). CONCLUSIONS: This study provides normative data for a novel self-administered tablet computer application that is ultimately designed to measure the individual risk for adverse postoperative cognitive outcomes in elderly patients.

Older Candidates for Subthalamic Deep Brain Stimulation in Parkinson's Disease Have a Higher Incidence of Psychiatric Serious Adverse Events.

OBJECTIVE: To investigate the incidence of serious adverse events (SAE) of subthalamic deep brain stimulation (STN-DBS) in elderly patients with Parkinson's disease (PD). METHODS: We investigated a group of 26 patients with PD who underwent STN-DBS at mean age 63.2 ± 3.3 years. The operated patients from the EARLYSTIM study (mean age 52.9 ± 6.6) were used as a comparison group. Incidences of SAE were compared between these groups. RESULTS: A higher incidence of psychosis and hallucinations was found in these elderly patients compared to the younger patients in the EARLYSTIM study (p < 0.01). CONCLUSIONS: The higher incidence of STN-DBS-related psychiatric complications underscores the need for comprehensive psychiatric pre- and postoperative assessment in older DBS candidates. However, these psychiatric SAE were transient, and the benefits of DBS clearly outweighed its adverse effects.

The Verbal Fluency Decline After Deep Brain Stimulation in Parkinson's Disease: Is There an Influence of Age?

BACKGROUND: DBS is commonly used to treat Parkinson's disease (PD). DBS is not considered to cause major cognitive side effects, but some research groups have reported that it can cause decreased verbal fluency. The influence of age on DBS cognitive outcome is unclear. We investigated the possible influence of patients' age, level of education, disease duration, disease progression, depression, and levodopa equivalent dose (LED) on verbal fluency performance in patients with PD who underwent DBS of the subthalamic nucleus (STN-DBS). In this article, we investigated the influence of demographic and clinical parameters, especially age, on cognitive performance post-DBS in PD patients. METHODS: Forty-three patients with PD and without major psychiatric illness (according to Diagnostic and Statistical Manual of Mental Disroders, Fourth Edition) were enrolled in the study. Median age was 64.0 years (range, 46-77). In 21 patients, the indication for DBS was established on clinical grounds in keeping with international guidelines; these patients underwent STN-DBS, and the remaining 22 did not. Cognitive performance in both groups was assessed by standard neuropsychological test batteries at baseline and after median follow-up of 7 months. RESULTS: A statistically significant decline in the semantic category of verbal fluency task was found in the STN-DBS group (P < 0.01). Linear regression model revealed an influence of age (P < 0.01) and disease duration (P < 0.01) in relation to this decline. CONCLUSIONS: This study confirms previous findings that verbal fluency declines after STN-DBS in PD patients in comparison to PD patients without DBS. This decline is related to age and disease duration.

Slowing of EEG background activity in Parkinson's and Alzheimer's disease with early cognitive dysfunction.

BACKGROUND: Slowing of the electroencephalogram (EEG) is frequent in Parkinson's (PD) and Alzheimer's disease (AD) and correlates with cognitive decline. As overlap pathology plays a role in the pathogenesis of dementia, it is likely that demented patients in PD show similar physiological alterations as in AD. OBJECTIVE: To analyze distinctive quantitative EEG characteristics in early cognitive dysfunction in PD and AD. METHODS: Forty patients (20 PD- and 20 AD patients with early cognitive impairment) and 20 normal controls (NC) were matched for gender, age, and education. Resting state EEG was recorded from 256 electrodes. Relative power spectra, median frequency (4-14 Hz), and neuropsychological outcome were compared between groups. RESULTS: Relative theta power in left temporal region and median frequency separated the three groups significantly (p = 0.002 and p < 0.001). Relative theta power was increased and median frequency reduced in patients with both diseases compared to NC. Median frequency was higher in AD than in PD and classified groups significantly (p = 0.02). CONCLUSION: Increase of theta power in the left temporal region and a reduction of median frequency were associated with presence of AD or PD. PD patients are characterized by a pronounced slowing as compared to AD patients. Therefore, in both disorders EEG slowing might be a useful biomarker for beginning cognitive decline.

BrainCheck - a very brief tool to detect incipient cognitive decline: optimized case-finding combining patient- and informant-based data.

INTRODUCTION: Optimal identification of subtle cognitive impairment in the primary care setting requires a very brief tool combining (a) patients' subjective impairments, (b) cognitive testing, and (c) information from informants. The present study developed a new, very quick and easily administered case-finding tool combining these assessments ('BrainCheck') and tested the feasibility and validity of this instrument in two independent studies. METHODS: We developed a case-finding tool comprised of patient-directed (a) questions about memory and depression and (b) clock drawing, and (c) the informant-directed 7-item version of the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). Feasibility study: 52 general practitioners rated the feasibility and acceptance of the patient-directed tool. Validation study: An independent group of 288 Memory Clinic patients (mean ± SD age = 76.6 ± 7.9, education = 12.0 ± 2.6; 53.8% female) with diagnoses of mild cognitive impairment (n = 80), probable Alzheimer's disease (n = 185), or major depression (n = 23) and 126 demographically matched, cognitively healthy volunteer participants (age = 75.2 ± 8.8, education = 12.5 ± 2.7; 40% female) partook. All patient and healthy control participants were administered the patient-directed tool, and informants of 113 patient and 70 healthy control participants completed the very short IQCODE. RESULTS: Feasibility study: General practitioners rated the patient-directed tool as highly feasible and acceptable. Validation study: A Classification and Regression Tree analysis generated an algorithm to categorize patient-directed data which resulted in a correct classification rate (CCR) of 81.2% (sensitivity = 83.0%, specificity = 79.4%). Critically, the CCR of the combined patient- and informant-directed instruments (BrainCheck) reached nearly 90% (that is 89.4%; sensitivity = 97.4%, specificity = 81.6%). CONCLUSION: A new and very brief instrument for general practitioners, 'BrainCheck', combined three sources of information deemed critical for effective case-finding (that is, patients' subject impairments, cognitive testing, informant information) and resulted in a nearly 90% CCR. Thus, it provides a very efficient and valid tool to aid general practitioners in deciding whether patients with suspected cognitive impairments should be further evaluated or not ('watchful waiting').

The Extension of the German CERAD Neuropsychological Assessment Battery with Tests Assessing Subcortical, Executive and Frontal Functions Improves Accuracy in Dementia Diagnosis.

BACKGROUND/AIMS: Alzheimer's disease (AD) is the most common form of dementia. Neuropsychological assessment of individuals with AD primarily focuses on tests of cortical functioning. However, in clinical practice, the underlying pathologies of dementia are unknown, and a focus on cortical functioning may neglect other domains of cognition, including subcortical and executive functioning. The current study aimed to improve the diagnostic discrimination ability of the Consortium to Establish a Registry for Alzheimer's Disease - Neuropsychological Assessment Battery (CERAD-NAB) by adding three tests of executive functioning and mental speed (Trail Making Tests A and B, S-Words). METHODS: Logistic regression analyses of 594 normal controls (NC), 326 patients with mild AD and 224 patients with other types of dementia (OD) were carried out, and the area under the curve values were compared to those of CERAD-NAB alone. RESULTS: All comparisons except AD-OD (65.5%) showed excellent classification rates (NC-AD: 92.7%; NC-OD: 89.0%; NC-all patients: 91.0%) and a superior diagnostic accuracy of the extended version. CONCLUSION: Our findings suggest that these three tests provide a sensible addition to the CERAD-NAB and can improve neuropsychological diagnosis of dementia.

Clinical EEG in cognitively impaired patients with Parkinson's Disease.

Parkinson's Disease Dementia (PD-D) is one of the most important non-motor signs in advanced PD and is the most influencing factor predicting nursing home placement. PD-related Mild Cognitive Impairment (PD-MCI) is a potential prodromal stage of PD-D. The Grand Total EEG (GTE) score is a rating scale for clinical EEG (Electroencephalography) analyses which is useful in the evaluation of different types of dementia. The purpose of the present study was to investigate the relationship between a short version of the GTE score and severity of cognitive deficits in PD. Nineteen patients with PD underwent neuropsychological testing and resting state EEG. Significant correlations with deteriorating cognition (combined Mini Mental Status Examination/Clock Drawing Test) were found for the overall short GTE score (Spearman Rank correlation, ρ=-.6; p<.05) and for the subscore "Frequency of Rhythmic Background Activity" (ρ=-.6; p<.05), indicating that these EEG measures increase with deteriorating cognition.

Early detection of Alzheimer's disease with a total score of the German CERAD.

The goal of the present study was to evaluate the diagnostic discriminability of three different global scores for the German version of the Consortium to Establish a Registry on Alzheimer's Disease-Neuropsychological Assessment Battery (CERAD-NAB). The CERAD-NAB was administered to 1100 healthy control participants [NC; Mini-Mental State Examination (MMSE) mean = 28.9] and 352 patients with very mild Alzheimer's disease (AD; MMSE mean = 26.1) at baseline and subsets of participants at follow-up an average of 2.4 (NC) and 1.2 (AD) years later. We calculated the following global scores: Chandler et al.'s (2005) score (summed raw scores), logistic regression on principal components analysis scores (PCA-LR), and logistic regression on demographically corrected CERAD-NAB variables (LR). Correct classification rates (CCR) were compared with areas under the receiver operating characteristics curves (AUC). The CCR of the LR score (AUC = .976) exceeded that of the PCA-LR, while the PCA-LR (AUC = .968) and Chandler (AUC = .968) scores performed comparably. Retest data improved the CCR of the PCA-LR and Chandler (trend) scores. Thus, for the German CERAD-NAB, Chandler et al.'s total score provided an effective global measure of cognitive functioning, whereby the inclusion of retest data tended to improve correct classification of individual cases.

[Delirium and dementia]. / Demenz und Delirium.

Dementia and delirium are nosologic entities with overlapping presenting symptoms. The diagnostic criteria of dementia and of mild cognitive impairment-conceptualized as prodromal state of dementia-are discussed here and the importance of very early diagnosis of cognitive decline and the integration of information from informants in the diagnostic process is highlighted. Prominent features of vascular dementia and of dementia with Lewy bodies which are important for differential diagnosis and therapy are described.

Screening properties of the German IQCODE with a two-year time frame in MCI and early Alzheimer's disease.

BACKGROUND: The Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE) is a widely used screening tool for dementia. We aimed to determine the ability of the German version of the 16-item IQCODE with a two-year time frame to discriminate healthy mature control participants (NC) from mild cognitive impairment (MCI) and probable early Alzheimer's disease (AD) patients (all with Mini-mental State Examination (MMSE) scores >or= 24/30) and to optimize diagnostic discriminability by shortening the IQCODE. METHODS: 453 NC (49.7% women, age = 69.5 years +/- 8.2, education = 12.2 +/- 2.9), 172 MCI patients (41.9% women, age = 71.5 years +/- 8.8, education = 12.3 +/- 3.1) and 208 AD patients (59.1% women, age = 76.0 years +/- 6.4, education = 11.4 +/- 2.9) participated. Stepwise binary logistic regression analyses (LR) were used to shorten the test. Receiver operating characteristic curves (ROC) determined sensitivities, specificities, and correct classification rates (CCRs) for (a) NC vs. all patients; (b) NC vs. MCI; and (c) NC vs. AD patients. RESULTS: The mean IQCODE was 3.00 for NC, 3.35 for MCI, and 3.73 for AD. CCRs were 85.5% (NC-patient group), 79.9% (NC-MCI), and 90.7% (NC-AD), respectively. The diagnostic discriminability of the shortened 7-item IQCODE (i.e. items 1, 2, 3, 5, 7, 10, 14) was comparable with the longer version (i.e. 7-item CCRs: NC-patient group: 85.3%; NC-MCI: 80.1%, NC-AD: 90.5%). CONCLUSIONS: The German 16-item IQCODE with two-year time frame showed excellent screening properties for MCI and early AD patients. An abbreviated 7-item version demonstrated equally high diagnostic discriminability, thus allowing for more economical screening.