Republished review: cataract and cognitive impairment: a review of the literature

Acquired cataract and cognitive impairment are both common age-related problems, and ophthalmologists are increasingly likely to encounter patients who have both. Patients with dementia types who display early visuoperceptual impairment may present first to ophthalmology services. When these patients have coexisting cataract, it may be difficult to distinguish visual complaints due to cataract from those due to dementia. The interaction between visual impairment due to cataract and neurodegenerative disorders affecting the central visual pathways, is not fully understood. Visual impairment due to cataract may stress impaired attentional mechanisms and cataract extraction may improve cognitive performance in some patients with early cognitive impairment; however, the benefits of cataract surgery in established dementia are less clear. In this study, the literature on this subject was reviewed and the implications for practice were considered.

Classification of Mild Cognitive Impairment and Alzheimer Disease Using Model-Based MR and Magnetization Transfer Imaging

Early stratification of degenerative processes is a prerequisite to warrant therapeutic options in prodromal Alzheimer disease. Our aim was to investigate differences in cerebral macromolecular tissue composition between patients with AD, mild cognitive impairment, and age- and sex-matched healthy controls by using model-based magnetization transfer with a binary spin-bath magnetization transfer model and magnetization transfer ratio at 1.5 T.

Cognitive impairment and cortical reorganization in children with benign epilepsy with centrotemporal spikes

Benign epilepsy with centrotemporal spikes (BECTS) is associated with mild cognitive deficits, especially language impairment. This study aimed to clarify whether children with BECTS with left- or right-hemispheric, or bilateral focus have specific neuropsychological language deficits when compared to healthy controls, whether these deficits correlate functionally with language network organization (typical vs. atypical), and whether cofactors such as duration, handedness, and medication have a relevant impact on language reorganization processes.

Reduced neuronal efficacy in progressive mild cognitive impairment: a prospective fMRI study on visuospatial processing

Mild cognitive impairment (MCI) often refers to the preclinical stage of dementia, where the majority develop Alzheimer's disease (AD). Given that neurodegenerative burden and compensatory mechanisms might exist before accepted clinical symptoms of AD are noticeable, the current prospective study aimed to investigate the functioning of brain regions in the visuospatial networks responsible for preclinical symptoms in AD using event-related functional magnetic resonance imaging (fMRI). Eighteen MCI patients were evaluated and clinically followed for approximately 3 years. Five progressed to AD (PMCI) and eight remained stable (SMCI). Thirteen age-, gender- and education-matched controls also participated. An angle discrimination task with varying task demands was used. Brain activation patterns as well as task demand-dependent and -independent signal changes between the groups were investigated by using an extended general linear model including individual performance (reaction time [RT]) of each single trial. Similar behavioral (RT and accuracy) responses were observed between MCI patients and controls. A network of bilateral activations, e.g. dorsal pathway, which increased linearly with increasing task demand, was engaged in all subjects. Compared with SMCI patients and controls, PMCI patients showed a stronger relation between task demand and brain activity in left superior parietal lobules (SPL) as well as a general task demand-independent increased activation in left precuneus. Altered brain function can be detected at a group level in individuals that progress to AD before changes occur at the behavioral level. Increased parietal activation in PMCI could reflect a reduced neuronal efficacy due to accumulating AD pathology and might predict future clinical decline in patients with MCI.

Decreased EEG synchronization in Alzheimer's disease and mild cognitive impairment

The hypothesis of a functional disconnection of neuro-cognitive networks in patients with mild cognitive impairment (MCI) and Alzheimer Dementia was investigated using baseline resting EEG data. EEG databases from New York (264 subjects) and Stockholm (155 subjects), including healthy controls and patients with varying degrees of cognitive decline or Alzheimer Dementia were analyzed using Global Field Synchronization (GFS), a novel measure of global EEG synchronization. GFS reflects the global amount of phase-locked activity at a given frequency by a single number; it is independent of the recording reference and of implicit source models. Patients showed decreased GFS values in Alpha, Beta, and Gamma frequency bands, and increased GFS values in the Delta band, confirming the hypothesized disconnection syndrome. The results are discussed within the framework of current knowledge about the functional significance of the affected frequency bands.

Reduction in rat phosphatidylethanolamine binding protein-1 (PEBP1) after chronic corticosterone treatment may be paralleled by cognitive impairment: a first study

Chronic stress is associated with hippocampal atrophy and cognitive dysfunction. This study investigates how long-lasting administration of corticosterone as a mimic of experimentally induced stress affects psychometric performance and the expression of the phosphatidylethanolamine binding protein (PEBP1) in the adult hippocampus of one-year-old male rats. Psychometric investigations were conducted in rats before and after corticosterone treatment using a holeboard test system. Rats were randomly attributed to 2 groups (n = 7) for daily subcutaneous injection of either 26.8 mg/kg body weight corticosterone or sesame oil (vehicle control). Treatment was continued for 60 days, followed by cognitive retesting in the holeboard system. For protein analysis, the hippocampal proteome was separated by 2D electrophoresis (2DE) followed by image processing, statistical analysis, protein identification via peptide mass fingerprinting and gel matching and subsequent functional network mapping and molecular pathway analysis. Differential expression of PEBP1 was additionally quantified by Western blot analysis. Results show that chronic corticosterone significantly decreased rat hippocampal PEBP1 expression and induced a working and reference memory dysfunction. From this, we derive the preliminary hypothesis that PEBP1 may be a novel molecular mediator influencing cognitive integrity during chronic corticosterone exposure in rat hippocampus.

Multi-parametric classification of Alzheimer's disease and mild cognitive impairment: the impact of quantitative magnetization transfer MR imaging

Multi-parametric and quantitative magnetic resonance imaging (MRI) techniques have come into the focus of interest, both as a research and diagnostic modality for the evaluation of patients suffering from mild cognitive decline and overt dementia. In this study we address the question, if disease related quantitative magnetization transfer effects (qMT) within the intra- and extracellular matrices of the hippocampus may aid in the differentiation between clinically diagnosed patients with Alzheimer disease (AD), patients with mild cognitive impairment (MCI) and healthy controls. We evaluated 22 patients with AD (n=12) and MCI (n=10) and 22 healthy elderly (n=12) and younger (n=10) controls with multi-parametric MRI. Neuropsychological testing was performed in patients and elderly controls (n=34). In order to quantify the qMT effects, the absorption spectrum was sampled at relevant off-resonance frequencies. The qMT-parameters were calculated according to a two-pool spin-bath model including the T1- and T2 relaxation parameters of the free pool, determined in separate experiments. Histograms (fixed bin-size) of the normalized qMT-parameter values (z-scores) within the anterior and posterior hippocampus (hippocampal head and body) were subjected to a fuzzy-c-means classification algorithm with downstreamed PCA projection. The within-cluster sums of point-to-centroid distances were used to examine the effects of qMT- and diffusion anisotropy parameters on the discrimination of healthy volunteers, patients with Alzheimer and MCIs. The qMT-parameters T2(r) (T2 of the restricted pool) and F (fractional pool size) differentiated between the three groups (control, MCI and AD) in the anterior hippocampus. In our cohort, the MT ratio, as proposed in previous reports, did not differentiate between MCI and AD or healthy controls and MCI, but between healthy controls and AD.

Childhood Trauma and PTSD symptoms increase the risk of cognitive impairment in a sample of former indetured child laborers in old Age.

A growing body of evidence suggests a link between early childhood trauma, post-traumatic stress disorder (PTSD) and higher risk for dementia in old age. The aim of the present study was to investigate the association between childhood trauma exposure, PTSD and neurocognitive function in a unique cohort of former indentured Swiss child laborers in their late adulthood. To the best of our knowledge this is the first study ever conducted on former indentured child laborers and the first to investigate the relationship between childhood versus adulthood trauma and cognitive function. According to PTSD symptoms and whether they experienced childhood trauma (CT) or adulthood trauma (AT), participants (n = 96) were categorized as belonging to one of four groups: CT/PTSD+, CT/PTSD-, AT/PTSD+, AT/PTSD-. Information on cognitive function was assessed using the Structured Interview for Diagnosis of Dementia of Alzheimer Type, Multi-infarct Dementia and Dementia of other Etiology according to ICD-10 and DSM-III-R, the Mini-Mental State Examination, and a vocabulary test. Depressive symptoms were investigated as a potential mediator for neurocognitive functioning. Individuals screening positively for PTSD symptoms performed worse on all cognitive tasks compared to healthy individuals, independent of whether they reported childhood or adulthood adversity. When controlling for depressive symptoms, the relationship between PTSD symptoms and poor cognitive function became stronger. Overall, results tentatively indicate that PTSD is accompanied by cognitive deficits which appear to be independent of earlier childhood adversity. Our findings suggest that cognitive deficits in old age may be partly a consequence of PTSD or at least be aggravated by it. However, several study limitations need to considered. Consideration of cognitive deficits when treating PTSD patients and victims of lifespan trauma (even without a diagnosis of a psychiatric condition) is crucial. Furthermore, early intervention may prevent long-term deficits in memory function and development of dementia in adulthood.

Effect of Cognitive Impairment on Driving-Relevant Cognition in Older Persons

Intact cognitive abilities are fundamental for driving. Driving-relevant cognition may be affected in older drivers due to aging or cognitive impairment. The aim of this study was to investigate the effects of cognitive impairment on driving-relevant cognition in older persons. Performance in selective and divided attention, eye-hand-coordination, executive functions and the ability to regulate distance and speed of 18 older persons with CI-Group (cognitive impairment group) was compared to performance of older control group (18 age and gender-matched cognitively normal subjects) and young control group (18 gender-matched young subjects). The CI-Group showed poorer performance than the other two control groups in all cognitive tasks (significance level (p) < 0.001, effect size (partial η2) = 0.63). Differences between cognitively impaired and cognitively normal subjects were still significant after controlling for age (effect sizes from 0.14 to 0.28). Dual tasking affected performance of cognitively impaired subjects more than performance of the other two groups (p = 0.016, partial η2 = 0.14). Results show that cognitive impairment has age-independent detrimental effects on selective and divided attention, eye-hand-coordination, executive functions and the ability to regulate distance and speed. Largest effect sizes are found for reaction times in attention tasks.

Tooth loss, chewing efficiency and cognitive impairment in geriatric patients.

BACKGROUND Patients with dementia have poorer oral health and fewer teeth than their peers without cognitive impairment. OBJECTIVE The hypothesis of this study is that the number of natural teeth and the chewing efficiency are associated with cognitive functioning. METHODS This cross-sectional study included 29 patients diagnosed with dementia aged 75 years or older and 22 controls who were either cognitively normal (n = 19) or with mild cognitive impairment (n = 3). Neuropsychological, nutritional and dental assessments were performed. The chewing efficiency was evaluated with a two-colour mixing test. RESULTS Demented patients and controls presented with a mean of 4.9 and 6.5 teeth, respectively (n.s.). The number of natural teeth was not associated with dementia (p = 0.553). Same results were found for age (p = 0.746) and sex (p = 0.901). The chewing efficiency by visual inspection proved worse in participants with dementia than in the controls (p < 0.011) and explained 9.3% of the variance in the diagnosis of dementia. Neither dental state nor chewing efficiency was related to the nutritional state. CONCLUSION Chewing efficiency seems stronger associated with cognitive impairment than the number of teeth. Hence, in a more holistic approach for the geriatric assessment, the dental examination may be complemented by a chewing efficiency test.

The feasibility of self-report advance directives among elderly patients with cognitive impairment

The central objective of this dissertation was to determine the feasibility of self-completed advance directives (AD) in older persons suffering from mild and moderate stages of dementia. This was accomplished by identifying differences in ability to complete AD among elderly subjects with increasing degrees of dementia and cognitive incompetence. Secondary objectives were to describe and compare advance directives completed by elders and identified proxy decision makers. Secondary objectives were accomplished by measuring the agreement between advance directives completed by proxy and elder, and comparing that agreement across groups defined by the elder's cognitive status. This cross-sectional study employed a structured interview to elicit AD, followed by a similar interview with a proxy decision maker identified by the elder. A stratified sampling scheme recruited elders with normal cognition, mild, and moderate forms of dementia using the Mini Mental-State Exam (MMSE). The Hopkins Competency Assessment Test (HCAT) was used for evaluation of competency to make medical decisions. Analysis was conducted on "between group" (non-demented $\leftrightarrow$ mild dementia $\leftrightarrow$ moderate dementia, and competent $\leftrightarrow$ incompetent) and "within group" (elder $\leftrightarrow$ family member) variation.^ The 118 elderly subjects interviewed were generally male, Caucasian, and of low socioeconomic status. Mean age was 77. Overall, elders preferred a "trial of therapy" regarding AD rather than to "always receive the therapy". No intervention was refused outright more often than it was accepted. A test-retest of elders' AD revealed stable responses. Eleven logic checks measured appropriateness of AD responses independent of preference. No difference was found in logic error rates between elders grouped by MMSE or HCAT. Agreement between proxy and elder responses showed significant dissimilarity, indicating that proxies were not making the same medical decisions as the elders.^ Conclusions based on these data are: (1) Self reporting AD is feasible among elders showing signs of cognitive impairment and they should be given all opportunities to complete advance directives, (2) variation in preferences for advance directives in cognitively impaired elders should not be assumed to be the effects of their impairment alone, (3) proxies do not appear to forego life-prolonging interventions in the face of increasing impairment in their ward, however, their advance directives choices are frequently not those of the elder they represent. ^

Dysfunctional and compensatory duality in mild cognitive impairment during a continuous recognition memory task

One of the current issues of debate in the study of mild cognitive impairment (MCI) is deviations of oscillatory brain responses from normal brain states and its dynamics. This work aims to characterize the differences of power in brain oscillations during the execution of a recognition memory task in MCI subjects in comparison with elderly controls. Magnetoencephalographic (MEG) signals were recorded during a continuous recognition memory task performance. Oscillatory brain activity during the recognition phase of the task was analyzed by wavelet transform in the source space by means of minimum norm algorithm. Both groups obtained a 77% hit ratio. In comparison with healthy controls, MCI subjects showed increased theta (p < 0.001), lower beta reduction (p < 0.001) and decreased alpha and gamma power (p < 0.002 and p < 0.001 respectively) in frontal, temporal and parietal areas during early and late latencies. Our results point towards a dual pattern of activity (increase and decrease) which is indicative of MCI and specific to certain time windows, frequency bands and brain regions. These results could represent two neurophysiological sides of MCI. Characterizing these opposing processes may contribute to the understanding of the disorder.

Alterations of cross-frequency coupling in MEG resting state recordings in Mild Cognitive Impairment patients

The default mode network (DMN) has received growing attention in recent years because it seems to be involved in the neuropathology of psychiatric and neurodegenerative disorders such as autism, schizophrenia and Alzheimer Disease. It has been defined as a task negative network, beca use the activity of all its brain regions is increased during the resting state and suspended during external or goal directed tasks.

Brain dynamics of mild cognitive impairment during face encoding

Brain oscillations are closely correlated with human information processing and fundamental aspects of cognition. Previous literature shows that due to the relation between brain oscillations and memory processes, spectral dynamics during such tasks are good candidates to study and characterize memory related pathologies. Mild cognitive impairment (MCI), defined as a clinical condition characterized by memory impairment and/ or deterioration of additional cognitive domains, is considered a preliminary stage in the dementia process. In consequence, the study of its brain patterns could help to achieve an early diagnosis of Alzheimer Disease.

Resting state functional connectivity patterns associated with ApoE genotype. A MEG study in Mild Cognitive Impairment (MCI)

Alteration of brain communication due to abnormal patterns of synchronization is nowadays one of the most suitable mechanisms for having a better understanding of brain pathologies. Very recently, it has been proved that abnormal changes in both local and long range functional interactions underlie the cognitive deficits associated with different brain disorders. Mild cognitive impairment (MCI) is a state characterized for cognitive dysfunction, such as the memory. The study of the spatial and dynamic alterations in MCI subjects' functional networks could provide important evidences of the brain mechanisms responsible for such impairment.