Differentiation of Alzheimer's disease based on local and global parameters in personalized Virtual Brain models.

Alzheimer's disease (AD) is marked by cognitive dysfunction emerging from neuropathological processes impacting brain function. AD affects brain dynamics at the local level, such as changes in the balance of inhibitory and excitatory neuronal populations, as well as long-range changes to the global network. Individual differences in these changes as they relate to behaviour are poorly understood. Here, we use a multi-scale neurophysiological model, "The Virtual Brain (TVB)", based on empirical multi-modal neuroimaging data, to study how local and global dynamics correlate with individual differences in cognition. In particular, we modeled individual resting-state functional activity of 124 individuals across the behavioural spectrum from healthy aging, to amnesic Mild Cognitive Impairment (MCI), to AD. The model parameters required to accurately simulate empirical functional brain imaging data correlated significantly with cognition, and exceeded the predictive capacity of empirical connectomes.

Roles of Education and IQ in Cognitive Reserve in Parkinson's Disease-Mild Cognitive Impairment.

BACKGROUND/AIMS: The role of cognitive reserve in Parkinson's disease (PD)-mild cognitive impairment (MCI) is incompletely understood. METHODS: The relationships between PD-MCI, years of education, and estimated premorbid IQ were examined in 119 consecutive non-demented PD patients using logistic regression models. RESULTS: Higher education and IQ were associated with reduced odds of PD-MCI in univariate analysis. In multivariable analysis, a higher IQ was associated with a significantly decreased odds of PD-MCI, but education was not. CONCLUSION: The association of higher IQ and decreased odds of PD-MCI supports a role for cognitive reserve in PD, but further studies are needed to clarify the interaction of IQ and education and the impact of other contributors such as employment and hobbies.

Dynamic allocation of attention in aging and Alzheimer disease: uncoupling of the eye and mind.

CONTEXT: Visual attention can be distributed focally, in the direction of gaze, or globally, throughout the extrapersonal space. Aging, and especially Alzheimer disease (AD), may influence global attention, resulting in shifts of gaze to attend to the global workspace. OBJECTIVE: To determine if subjects who have AD and cognitively intact older subjects shift their gaze more often than young subjects while viewing a dynamic stimulus that emphasizes global attention. DESIGN: Experimental study of eye fixation patterns in response to a simulated driving scene with stationary and moving distractors. SETTING: Urban, medical school, National Institute on Aging-funded Alzheimer's Disease Center. PARTICIPANTS: Thirteen subjects with mild probable AD, 13 age-comparable cognitively intact older control subjects, and 11 young control subjects. MAIN OUTCOME MEASURE: Proportion of eye fixations within and outside of a central region of interest encompassing the "road" surface. RESULTS: Young controls made significantly more eye fixations (mean number of eye fixations, 47.5) than either of the other 2 groups (older controls mean, 33.2; patients with AD mean, 32.2). However, 76% of their fixations remained within the central region of interest. Older controls and subjects with AD made proportionately fewer fixations within this region (48% and 49%, respectively) than young controls and moved their eyes more often to the periphery but did not differ from one another. CONCLUSIONS: Young controls maintain central eye position regardless of peripheral distraction. Older controls move their eyes to the periphery, presumably to widen the window of attention. Subjects with mild AD did not experience an additional disadvantage beyond that associated with aging.

[Beyond "successful aging: Rembrandt in his self-portraits]. / Uber "Successful Aging" hinaus: Rembrandt in seinen Selbstbildnissen.

The process of aging has been generally associated with cognitive dedine. However, some complex cognitive abilities, such as wisdom and judgement, have been suggested to improve with age. In the current study, the development of an advanced artistic ability is examined over the life span of Rembrandt H. van Rijn. Analysis of the paintings revealed the development of an old-age-style in the last portrait, characterised by uniformity of texture, facture, and lighting. The self-portrait painted in the last year of Rembrandt's life reflects a high degree of integration of artistic skill and experience gathered in the course of life, and hence reflects features of wisdom in the sence suggested by Baltes. The development of a mature "late" style can help to characterise the emergence of qualitatively different and advanced cognitive abilities in old age.

Alterations of visual search strategy in Alzheimer's disease and aging.

Visual search, characterized by eye fixation patterns, was examined in 8 patients with Alzheimer's disease (AD), 8 cognitively intact, age-matched individuals, and 8 young control participants as they searched for a number among a nonlinear array of letters on a large computer screen. Among the 3 groups, target detection accuracy differed and detection time increased linearly. There were more fixations, and fixation duration was significantly longer in the AD patients than in the other 2 groups. These factors contributed to the lengthening of target detection time. This qualitative difference in the architecture of visual search between AD and aging may reflect a specific deficit in the disengagement of visual spatial attention, a prolongation of saccade initiation, or inefficiency in planning a search strategy.

Dopamine agonists reorient visual exploration away from the neglected hemispace.

OBJECTIVE: To study the effects of bromocriptine, a dopamine agonist, on visual search. BACKGROUND: The anatomic substrate of spatial attention takes the form of a distributed network with interconnected cortical (frontal, parietal, and cingulate) and subcortical (striatal and thalamic) components. Dopamine appears to exert a modulatory effect on the function of this network. METHODS: Seven consecutive right-handed subjects with right-sided cerebral lesions were studied using a computerized target search paradigm. Eye movements were recorded. RESULTS: Bromocriptine caused the subjects to spend more time exploring the ipsilesional hemispace and therefore increased the relative neglect of the contralesional left hemispace. However, target detection accuracy did not change. Bromocriptine thus had a differential impact on the exploratory-motor versus sensory-perceptual components of directed attention. CONCLUSIONS: Our results show that bromocriptine may worsen some aspects of hemispatial neglect in patients with lesions that include the postsynaptic components of ascending dopaminergic pathways.