Performance on complex memory tests is associated with ß-amyloid in individuals at risk of developing Alzheimer's disease.

The pathophysiological development of Alzheimer's disease (AD) begins in the brain years before the onset of clinical symptoms. The accumulation of beta-amyloid (Aß) is thought to be the first cortical pathology to occur. Carrying one apolipoprotein E (APOE) ε4 allele increases the risk of developing AD at least 2-3 times and is associated with earlier Aß accumulation. Although it is difficult to identify Aß-related cognitive impairment in early AD with standard cognitive tests, more sensitive memory tests may be able to do this. We sought to examine associations between Aß and performance on three tests within three subdomains of memory, verbal, visual, and associative memory, to elucidate which of these tests were sensitive to Aß-related cognitive impairment in at-risk subjects. 55 APOE ε4 carriers underwent MRI, 11 C-Pittsburgh Compound B (PiB) PET, and cognitive testing. A composite cortical PiB SUVR cut-off score of 1.5 was used to categorise subjects as either APOE ε4 Aß+ or APOE ε4 Aß-. Correlations were carried out using cortical surface analysis. In the whole APOE ε4 group, we found significant correlations between Aß load and performance on verbal, visual, and associative memory tests in widespread cortical areas, the strongest association being with performance on associative memory tests. In the APOE ε4 Aß+ group, we found significant correlations between Aß load and performance of verbal and associative, but not visual, memory in localised cortical areas. Performance on verbal and associative memory tests provides sensitive markers of early Aß-related cognitive impairment in at-risk subjects.

Cognitive Dysfunction in Non-Alcoholic Fatty Liver Disease-Current Knowledge, Mechanisms and Perspectives.

Non-alcoholic fatty liver disease (NAFLD) has emerged as the hepatic component of the metabolic syndrome and now seemingly affects one-fourth of the world population. Features associated with NAFLD and the metabolic syndrome have frequently been linked to cognitive dysfunction, i.e. systemic inflammation, vascular dysfunction, and sleep apnoea. However, emerging evidence suggests that NAFLD may be a cause of cognitive dysfunction independent of these factors. NAFLD in addition exhibits dysbiosis of the gut microbiota and impaired urea cycle function, favouring systemic ammonia accumulation and further promotes systemic inflammation. Such disruption of the gut-liver-brain axis is essential in the pathogenesis of hepatic encephalopathy, the neuropsychiatric syndrome associated with progressive liver disease. Considering the growing burden of NAFLD, the morbidity from cognitive impairment is expected to have huge societal and economic impact. The present paper provides a review of the available evidence for cognitive dysfunction in NAFLD and outlines its possible mechanisms. Moreover, the clinical challenges of characterizing and diagnosing cognitive dysfunction in NAFLD are discussed.

Applied strategy in the Iowa Gambling Task: Comparison of individuals with Parkinson's disease to healthy controls.

INTRODUCTION: Decision-making impairments in Parkinson's disease (PD) have frequently been measured using the Iowa Gambling Task (IGT), though results have been inconsistent. At present, task performance has primarily been evaluated based on the total IGT score, and there is a need for further analysis of the strategy of older individuals with PD and healthy control (HC) participants in IGT. OBJECTIVE: The present study aims to explore possible impairments in IGT performance in individuals with PD compared to healthy controls using strategy analysis, extending previous results on this subject, and to discuss potential effects of medication on task performance. METHODS: 67 individuals with PD and 29 HC participants completed the IGT. Results were analyzed to evaluate impairments, applied strategies, presence of subgroups, and potential effects of medication on performance. RESULTS: Both groups obtained a low overall IGT score and individuals with PD had significantly lower total IGT scores compared to HC participants. Regression analysis showed a small, but significant relationship between levodopa and dopamine agonist dosage and total IGT score, indicating that medication level could be a marker of level of executive functions. Subgroups of advantageous and disadvantageous choosers differed significantly in deck preferences for both groups. CONCLUSION: Individuals with PD were significantly impaired in IGT performance, both in overall scores and in detailed analyses, and they utilized an inefficient strategy during task performance. However, HC participants also presented with a suboptimal strategy and results suggest the presence of subgroups in both individuals with PD and HC participants, which may reflect age-related changes. These results are in line with previous research on performance of older individuals and alternative deck preferences in the IGT and underline the importance of considering the applied strategy in the evaluation of IGT performance.

Subjective cognitive complaints in patients with Parkinson's disease.

Mild cognitive impairment (MCI) is common in Parkinson's disease (PD), affecting almost all patients with PD at some time. It has been shown that patients with PD, who express subjective cognitive complaints, are at a higher risk of eventually developing PD-MCI. This is corroborated by the Movement Disorders Society's (MDS) diagnostic criteria from 2012 for PD-MCI, from which it follows that a subjective cognitive complaint must be present in addition to objective cognitive impairment for a patient with PD to receive a diagnosis of PD-MCI. Nevertheless, there is currently no standardized measurement available for assessing subjective cognitive complaints. Therefore, this review aims to generate an overview of how subjective cognitive complaints are commonly operationalized in the empirical literature as well as whether they are found to be associated with the level of cognitive impairment. The findings revealed that a broad range of measures has been used to obtain subjective cognitive complaints and that there is little consistency between different studies with regard to how they have obtained these complaints, from whom they had obtained them, how many they have obtained, which types of complaints they have obtained and whether they were associated with cognitive impairment. Given the fact that the presence of subjective cognitive complaints is a requirement for setting a diagnosis, there is a need for more methodological consensus with regard to the measurement hereof.

In Vivo cortical tau in Parkinson's disease using 18F-AV-1451 positron emission tomography.

BACKGROUND: Alzheimer's disease copathology is common in PD at autopsy. In non-PD subjects with mild cognitive impairment, tau depositions can be detected using 18F-AV-1451 PET. We hypothesized that 18F-AV-1451 PET would show tau aggregation in PD with mild cognitive impairment and correlate with cognitive dysfunction. OBJECTIVES: To describe tau aggregation in PD patients. METHODS: Twenty-six PD patients and 23 controls had 18F-AV-1451 PET and neuropsychological assessment to detect mild cognitive impairment. RESULTS: Nine PD patients (35%) were identified with mild cognitive impairment. Regional analyses showed no significant differences between groups. Voxel-wise analyses showed no correlation with cognitive domain z-scores within patients. One patient with mild cognitive impairment was estimated Braak tau stage 5; all other patients were stage 0. CONCLUSION: Our results indicate that tau pathology, as detected by 18F-AV-1451, is uncommon in PD with mild cognitive impairment and shows no significant correlation with cognitive dysfunction at this stage. © 2017 International Parkinson and Movement Disorder Society.

Odor identification deficits identify Parkinson's disease patients with poor cognitive performance.

Olfactory dysfunction is a prodromal and prevalent nonmotor symptom of Parkinson's disease. Unlike olfactory dysfunction in Alzheimer's disease, it is believed to be unrelated to cognitive impairment. However, recent research has implicated cholinergic denervation in Parkinson's disease hyposmia and linked it to verbal memory. This research hypothesized that severe odor identification deficits may identify patients with Parkinson's disease at risk for cognitive impairment. The current study tested this hypothesis by comparing 24 functionally anosmic, nondemented patients with Parkinson's disease and 39 nonanosmic, nondemented patients with Parkinson's disease with 29 healthy control participants on composite scores of memory, processing speed, executive function, and language. The functionally anosmic group had significantly poorer visual and verbal memory than the nonanosmic group, which was indistinguishable from the control group. Furthermore, the functionally anosmic group had reduced processing speed compared with the nonanosmic patients with Parkinson's disease, who, in turn, were outperformed by the control group. On the composite language score, the score of the functionally anosmic group was significantly reduced compared with that of the control group, whereas the nonanosmic group scored in the medium range. The 2 patient groups did not differ on executive functioning. These findings demonstrate co-occurrence between reduced cognitive function and olfactory deficits in functionally anosmic patients with Parkinson's disease and support the notion of more severe cognitive deficits in this group.

The parkinsonian personality and concomitant depression.

Parkinson's disease (PD) has been associated with a distinctive parkinsonian personality, characterized by conscientiousness, punctuality, industriousness, and reduced novelty-seeking, as compared with healthy elderly persons. Similar traits are identified in relation to depression. The objective of the study was to elucidate the relationship between the parkinsonian personality and depression. Thirty-two depressed and 86 nondepressed PD patients and 30 healthy control subjects completed the NEO-Personality Inventory Revised Short Version. PD patients with depression displayed a distinct personality profile, with increased Neuroticism and reduced Extroversion, as compared with nondepressed PD patients and control subjects. It seems plausible that a subgroup of PD patients possesses a distinct personality profile that renders them sensitive to development of depression, although the reverse might also be possible.