Decreased Electroencephalography Global Field Synchronization in Slow-Frequency Bands Characterizes Synaptic Dysfunction in Amnestic Subtypes of Mild Cognitive Impairment.

Background: Mild cognitive impairment (MCI) is highly prevalent in a memory clinic setting and is heterogeneous regarding its clinical presentation, underlying pathophysiology, and prognosis. The most prevalent subtypes are single-domain amnestic MCI (sd-aMCI), considered to be a prodromal phase of Alzheimer's disease (AD), and multidomain amnestic MCI (md-aMCI), which is associated with multiple etiologies. Since synaptic loss and dysfunction are the closest pathoanatomical correlates of AD-related cognitive impairment, we aimed to characterize it in patients with sd-aMCI and md-aMCI by means of resting-state electroencephalography (EEG) global field power (GFP), global field synchronization (GFS), and novel cerebrospinal fluid (CSF) synaptic biomarkers. Methods: We included 52 patients with sd-aMCI (66.9 ± 7.3 years, 52% women) and 30 with md-aMCI (63.1 ± 7.1 years, 53% women). All patients underwent a detailed clinical assessment, resting-state EEG recordings and quantitative analysis (GFP and GFS in delta, theta, alpha, and beta bands), and analysis of CSF biomarkers of synaptic dysfunction, neurodegeneration, and AD-related pathology. Cognitive subtyping was based on a comprehensive neuropsychological examination. The Mini-Mental State Examination (MMSE) was used as an estimation of global cognitive performance. EEG and CSF biomarkers were included in a multivariate model together with MMSE and demographic variables, to investigate differences between sd-aMCI and md-aMCI. Results: Patients with sd-aMCI had higher CSF phosphorylated tau, total tau and neurogranin levels, and lower values in GFS delta and theta. No differences were observed in GFP. The multivariate model showed that the most important synaptic measures for group separation were GFS theta, followed by GFS delta, GFP theta, CSF neurogranin, and GFP beta. Conclusion: Patients with sd-aMCI when compared with those with md-aMCI have a neurophysiological and biochemical profile of synaptic damage, neurodegeneration, and amyloid pathology closer to that described in patients with AD. The most prominent signature in sd-aMCI was a decreased global synchronization in slow-frequency bands indicating that functional connectivity in slow frequencies is more specifically related to early effects of AD-specific molecular pathology.

The Executive Checklist (EC-10) - a new rating instrument for clinicians assessing dysexecutive behavior.

Assessment of executive functions (EF) is often criticized for its lack of ecological validity. As a consequence, several self- and partner rating scales for EF have been developed, while rating scales designed for clinicians are lacking. We therefore developed the Executive Checklist (EC-10), a new rating scale for clinicians assessing dysexecutive behavior during neuropsychological assessment and examined its psychometric properties. Consecutive referrals from a memory clinic with subjective cognitive impairment (SCI; n = 27), mild cognitive impairment (MCI; n = 29), dementia (DEM; n = 16), as well as 11 healthy controls were assessed with the EC-10 while performing common neuropsychological tests. Results showed that the EC-10 had excellent inter-rater reliability, good internal consistency and modest relations to cognitive laboratory measures. The EC-10 increased the classification rate above and beyond the influence of neuropsychological tests when comparing patients with SCI and MCI or between cognitively impaired and non-impaired patients. Conclusively, the present study demonstrates that clinical observations can be quantified using the EC-10 and that this rating provides valuable information. As executive deficits are common in many neurological and neuropsychiatric disorders, validating the EC-10 in broader patient groups should be an important avenue for future research.

Self- and informant ratings of personality in mild cognitive impairment, reviewed.

AIMS: To examine the degree of agreement between self- and informant ratings of personality in relation to cognitive function in patients with mild cognitive impairment (MCI), subjective cognitive impairment (SCI) and healthy controls (HC). METHODS: Thirty-two patients and informants with MCI, 23 with SCI and 22 HC completed the Swedish universities Scales of Personality (SSP). Correlations and incongruence between self- and informant ratings were calculated. The Mini Mental State Examination (MMSE) was used to assess cognitive function. RESULTS: The correlations between self- and informant ratings were fair-to-moderate on a majority of SSP scales and significant in 44%. The incongruence between patients and informants was significantly larger in MCI than in HC across SSP scales. There was a significant negative correlation between the incongruence index and the MMSE for all subjects. CONCLUSIONS: Self-informant agreement on ratings of patients' personality was reasonable. Incongruence between patients and their informants was associated with MCI but not SCI or HC. Disagreement between patients and informants indicates cognitive impairment.

Personality features in subjective cognitive impairment and mild cognitive impairment--early indicators of dementia?

OBJECTIVES: The purpose of the present study was to investigate patterns of personality in patients with subjective cognitive impairment (SCI) and mild cognitive impairment (MCI), compared to healthy controls. METHODS: We assessed24 patients with SCI, 35 patients with MCI and 26 healthy controls with the self-report questionnaire Swedish Universities Scales of Personality measuring aspects of neuroticism/anxiety proneness, extraversion, and aggression-hostility. RESULTS: Patients with SCI and MCI showed significantly more Somatic Trait Anxiety, Psychic Trait Anxiety and Stress Susceptibility than healthy controls. Moreover, there was a significant increase in Detachment in patients with MCI and a significant decrease in Adventure Seeking in patients with SCI, relative to healthy controls. CONCLUSIONS: Patients with SCI and MCI presented specific patterns of personality alterations with higher scores in traits related to anxiety proneness and aggression-hostility and lower in traits of extraversion. In most subscales differences followed a sequential pattern with gradually increasing scores from healthy controls, to patients with SCI and further to MCI. The groups differed in amount and type of symptoms, suggesting that patterns of personality may be related to degree of cognitive impairment.

Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound-B.

This report describes the first human study of a novel amyloid-imaging positron emission tomography (PET) tracer, termed Pittsburgh Compound-B (PIB), in 16 patients with diagnosed mild AD and 9 controls. Compared with controls, AD patients typically showed marked retention of PIB in areas of association cortex known to contain large amounts of amyloid deposits in AD. In the AD patient group, PIB retention was increased most prominently in frontal cortex (1.94-fold, p = 0.0001). Large increases also were observed in parietal (1.71-fold, p = 0.0002), temporal (1.52-fold, p = 0.002), and occipital (1.54-fold, p = 0.002) cortex and the striatum (1.76-fold, p = 0.0001). PIB retention was equivalent in AD patients and controls in areas known to be relatively unaffected by amyloid deposition (such as subcortical white matter, pons, and cerebellum). Studies in three young (21 years) and six older healthy controls (69.5 +/- 11 years) showed low PIB retention in cortical areas and no significant group differences between young and older controls. In cortical areas, PIB retention correlated inversely with cerebral glucose metabolism determined with 18F-fluorodeoxyglucose. This relationship was most robust in the parietal cortex (r = -0.72; p = 0.0001). The results suggest that PET imaging with the novel tracer, PIB, can provide quantitative information on amyloid deposits in living subjects.