Functional Deficits in Patients with Mild Cognitive Impairment: Prediction of Ad

Objective: To evaluate the predictive utility of self-reported and informant-reported functional deficits in patients with mild cognitive impairment (MCI) for the follow-up diagnosis of probable AD. Methods: The Pfeffer Functional Activities Questionnaire (FAQ) and Lawton Instrumental Activities of Daily Living (IADL) Scale were administered at baseline. Patients were followed at 6-month intervals, and matched normal control subjects (NC) were followed annually. Results: Self-reported deficits were higher for patients with MCI than for NC. At baseline, self- and informant-reported functional deficits were significantly greater for patients who converted to AD on follow-up evaluation than for patients who did not convert, even after controlling for age, education, and modified Mini-Mental State Examination scores. While converters showed significantly more informant- than self-reported deficits at baseline, nonconverters showed the reverse pattern. Survival analyses further revealed that informant-reported deficits (but not self-reported deficits) and a discrepancy score indicating greater informant- than self-reported functional deficits significantly predicted the development of AD. The discrepancy index showed high specificity and sensitivity for progression to AD within 2 years. Conclusions: These findings indicate that in patients with MCI, the patient's lack of awareness of functional deficits identified by informants strongly predicts a future diagnosis of AD. If replicated, these findings suggest that clinicians evaluating MCI patients should obtain both self-reports and informant reports of functional deficits to help in prediction of long-term outcome

Exciton swapping in a twisted graphene bilayer as a solid-state realization of a two-brane model

It is shown that exciton swapping between two graphene sheets may occur under specific conditions. A magnetically tunable optical filter is described to demonstrate this new effect. Mathematically, it is shown that two turbostratic graphene layers can be described as a "noncommutative" two-sheeted (2+1)-spacetime thanks to a formalism previously introduced for the study of braneworlds in high energy physics. The Hamiltonian of the model contains a coupling term connecting the two layers which is similar to the coupling existing between two braneworlds at a quantum level. In the present case, this term is related to a K-K' intervalley coupling. In addition, the experimental observation of this effect could be a way to assess the relevance of some theoretical concepts of the braneworld hypothesis.Comment: 15 pages, 3 figures, final version published in European Physical Journal

Detection of early Alzheimer's disease in MCI patients by the combination of MMSE and an episodic memory test

BACKGROUND: Mild cognitive impairment (MCI) is a heterogeneous clinical entity that comprises the prodromal phase of Alzheimer's disease (Pr-AD). New biomarkers are useful in detecting Pr-AD, but they are not universally available. We aimed to investigate baseline clinical and neuropsychological variables that might predict progression from MCI to AD dementia. METHODS: All patients underwent a complete clinical and neuropsychological evaluation at baseline and every 6 months during a two-year follow-up period, with 54 out of 109 MCI patients progressing to dementia (50 of them progressed to AD dementia), and 55 remaining as stable MCI (S-MCI). RESULTS: A combination of MMSE and California Verbal Learning Test Long Delayed Total Recall (CVLT-LDTR) constituted the best predictive model: subjects scoring above 26/30 on MMSE and 4/16 on CVLT-LDTR had a negative predictive value of 93.93% at 2 years, whereas those subjects scoring below both of these cut-off scores had a positive predictive value of 80.95%. CONCLUSIONS: Pr-AD might be distinguished from S-MCI at baseline using the combination of MMSE and CVLT-LDTR. These two neuropsychological predictors are relatively brief and may be readily completed in non-specialist clinical settings

Executive deficits are related to the inferior frontal junction in early dementia

Executive functions describe a wide variety of higher order cognitive processes that allow the flexible modification of thought and behaviour in response to changing cognitive or environmental contexts. Their impairment is common in neurodegenerative disorders. Executive deficits negatively affect everyday activities and hamper the ability to cope with other deficits, such as memory impairment in Alzheimer's disease or behavioural disorders in frontotemporal lobar degeneration. Our study aimed to characterize the neural correlates of executive functions by relating respective deficits to regional hypometabolism in early dementia. Executive functions were assessed with two classical tests, the Stroop and semantic fluency test and various subtests of the behavioural assessment of the dysexecutive syndrome test battery capturing essential aspects of executive abilities relevant to daily living. Impairments in executive functions were correlated with reductions in brain glucose utilization as measured by [18F]fluorodeoxyglucose positron emission tomography and analysed voxelwise using statistical parametric mapping in 54 subjects with early dementia, mainly Alzheimer's disease and frontotemporal lobar degeneration, and its prodromal stages: subjective and mild cognitive impairment. Although the analysis revealed task-specific frontoparietal networks, it consistently showed that hypometabolism in one region in the left lateral prefrontal cortex—the inferior frontal junction area—was related to performance in the various neuropsychological tests. This brain region has recently been related to the three component processes of cognitive control—working memory, task switching and inhibitory control. Group comparisons additionally showed hypometabolism in this area in Alzheimer's disease and frontotemporal lobar degeneration. Our study underlines the importance of the inferior frontal junction area for cognitive control in general and for executive deficits in early dementia

Chemosensory Cues to Conspecific Emotional Stress Activate Amygdala in Humans

Alarm substances are airborne chemical signals, released by an individual into the environment, which communicate emotional stress between conspecifics. Here we tested whether humans, like other mammals, are able to detect emotional stress in others by chemosensory cues. Sweat samples collected from individuals undergoing an acute emotional stressor, with exercise as a control, were pooled and presented to a separate group of participants (blind to condition) during four experiments. In an fMRI experiment and its replication, we showed that scanned participants showed amygdala activation in response to samples obtained from donors undergoing an emotional, but not physical, stressor. An odor-discrimination experiment suggested the effect was primarily due to emotional, and not odor, differences between the two stimuli. A fourth experiment investigated behavioral effects, demonstrating that stress samples sharpened emotion-perception of ambiguous facial stimuli. Together, our findings suggest human chemosensory signaling of emotional stress, with neurobiological and behavioral effects

Everyday episodic memory in amnestic mild cognitive impairment: a preliminary investigation

<p>Abstract</p> <p>Background</p> <p>Decline in episodic memory is one of the hallmark features of Alzheimer's disease (AD) and is also a defining feature of amnestic Mild Cognitive Impairment (MCI), which is posited as a potential prodrome of AD. While deficits in episodic memory are well documented in MCI, the nature of this impairment remains relatively under-researched, particularly for those domains with direct relevance and meaning for the patient's daily life. In order to fully explore the impact of disruption to the episodic memory system on everyday memory in MCI, we examined participants' episodic memory capacity using a battery of experimental tasks with real-world relevance. We investigated episodic acquisition and delayed recall (story-memory), associative memory (face-name pairings), spatial memory (route learning and recall), and memory for everyday mundane events in 16 amnestic MCI and 18 control participants. Furthermore, we followed MCI participants longitudinally to gain preliminary evidence regarding the possible predictive efficacy of these real-world episodic memory tasks for subsequent conversion to AD.</p> <p>Results</p> <p>The most discriminating tests at baseline were measures of acquisition, delayed recall, and associative memory, followed by everyday memory, and spatial memory tasks, with MCI patients scoring significantly lower than controls. At follow-up (mean time elapsed: 22.4 months), 6 MCI cases had progressed to clinically probable AD. Exploratory logistic regression analyses revealed that delayed associative memory performance at baseline was a potential predictor of subsequent conversion to AD.</p> <p>Conclusions</p> <p>As a preliminary study, our findings suggest that simple associative memory paradigms with real-world relevance represent an important line of enquiry in future longitudinal studies charting MCI progression over time.</p

Prediction of Dementia in Primary Care Patients

BACKGROUND: Current approaches for AD prediction are based on biomarkers, which are however of restricted availability in primary care. AD prediction tools for primary care are therefore needed. We present a prediction score based on information that can be obtained in the primary care setting. METHODOLOGY/PRINCIPAL FINDINGS: We performed a longitudinal cohort study in 3.055 non-demented individuals above 75 years recruited via primary care chart registries (Study on Aging, Cognition and Dementia, AgeCoDe). After the baseline investigation we performed three follow-up investigations at 18 months intervals with incident dementia as the primary outcome. The best set of predictors was extracted from the baseline variables in one randomly selected half of the sample. This set included age, subjective memory impairment, performance on delayed verbal recall and verbal fluency, on the Mini-Mental-State-Examination, and on an instrumental activities of daily living scale. These variables were aggregated to a prediction score, which achieved a prediction accuracy of 0.84 for AD. The score was applied to the second half of the sample (test cohort). Here, the prediction accuracy was 0.79. With a cut-off of at least 80% sensitivity in the first cohort, 79.6% sensitivity, 66.4% specificity, 14.7% positive predictive value (PPV) and 97.8% negative predictive value of (NPV) for AD were achieved in the test cohort. At a cut-off for a high risk population (5% of individuals with the highest risk score in the first cohort) the PPV for AD was 39.1% (52% for any dementia) in the test cohort. CONCLUSIONS: The prediction score has useful prediction accuracy. It can define individuals (1) sensitively for low cost-low risk interventions, or (2) more specific and with increased PPV for measures of prevention with greater costs or risks. As it is independent of technical aids, it may be used within large scale prevention programs