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.

Subclinical thyroid dysfunction and cognitive decline in old age

BACKGROUND Subclinical thyroid dysfunction has been implicated as a risk factor for cognitive decline in old age, but results are inconsistent. We investigated the association between subclinical thyroid dysfunction and cognitive decline in the PROspective Study of Pravastatin in the Elderly at Risk (PROSPER). METHODS Prospective longitudinal study of men and women aged 70-82 years with pre-existing vascular disease or more than one risk factor to develop this condition (N = 5,154). Participants taking antithyroid medications, thyroid hormone supplementation and/or amiodarone were excluded. Thyroid function was measured at baseline: subclinical hyper- and hypothyroidism were defined as thyroid stimulating hormones (TSH) <0.45 mU/L or >4.50 mU/L respectively, with normal levels of free thyroxine (FT4). Cognitive performance was tested at baseline and at four subsequent time points during a mean follow-up of 3 years, using five neuropsychological performance tests. RESULTS Subclinical hyperthyroidism and hypothyroidism were found in 65 and 161 participants, respectively. We found no consistent association of subclinical hyper- or hypothyroidism with altered cognitive performance compared to euthyroid participants on the individual cognitive tests. Similarly, there was no association with rate of cognitive decline during follow-up. CONCLUSION We found no consistent evidence that subclinical hyper- or hypothyroidism contribute to cognitive impairment or decline in old age. Although our data are not in support of treatment of subclinical thyroid dysfunction to prevent cognitive dysfunction in later life, only large randomized controlled trials can provide definitive evidence.

Apolipoprotein E genotypes and cognitive functions in healthy elderly persons

Objectives- We investigated whether apoE genotypes correlate with cognitive functions in clinically healthy persons. Methods - In 1993 and 1995, we measured information processing speed, delayed free recall and semantic aspects of long-term memory in 227 men and 105 women aged 65 and over, a randomly selected subsample of the prospective Basel Study. Cardiovascular risk factors and education were assessed. Results -E2 were more prevalent in old-old (>75 years, 23.5% vs 15%) compared to E4 than in young-old (<75 years, 19.3% vs 23.5%). Taking into account age and education, subjects with ɛ3/ɛ4 or ɛ4/ɛ4 alleles (E4) performed lowest in all 3 tests compared to those homozygous for ɛ3 (E3) or carriers of one or two ɛ2 alleles (E2) (reaction time P=0.009, free recall P=0.05, WAIS-R vocabulary P<0.05). In old-old there was a significant difference between E2 and E4 for reaction time (P=0.02) and free recall (P<0.02) but not for vocabulary (P=0.086). In all 3 groups there were no significant changes after 2 years. The subgroup with the genotype ɛ2/ɛ4 performed consistently best in the cognitive tests. Cholesterol was significantly increased in the E4 and E3 group compared to the E2 group. Conclusion - ApoE genotype correlates with cognitive performance. The increased prevalence of E2 in the old-old and the significantly lower plasma cholesterol levels suggest differential morbidity and mortality as important factors influencing the prevalence of cognitive disorders in late life.

Cognitive and emotional effects of carotid stenosis

PRINCIPLES Patients with carotid artery stenosis (CAS) are at risk of ipsilateral stroke and chronic compromise of cerebral blood flow. It is under debate whether the hypo-perfusion or embolism in CAS is directly related to cognitive impairment. Alternatively, CAS may be a marker for underlying risk factors, which themselves influence cognition. We aimed to determine cognitive performance level and the emotional state of patients with CAS. We hypothesised that patients with high grade stenosis, bilateral stenosis, symptomatic patients and/or those with relevant risk factors would suffer impairment of their cognitive performance and emotional state. METHODS A total of 68 patients with CAS of ≥70% were included in a prospective exploratory study design. All patients underwent structured assessment of executive functions, language, verbal and visual memory, motor speed, anxiety and depression. RESULTS Significantly more patients with CAS showed cognitive impairments (executive functions, word production, verbal and visual memory, motor speed) and anxiety than expected in a normative sample. Bilateral and symptomatic stenosis was associated with slower processing speed. Cognitive performance and anxiety level were not influenced by the side and the degree of stenosis or the presence of collaterals. Factors associated with less cognitive impairment included higher education level, female gender, ambidexterity and treated hypercholesterolemia. CONCLUSIONS Cognitive impairment and increased level of anxiety are frequent in patients with carotid stenosis. The lack of a correlation between cognitive functioning and degree of stenosis or the presence of collaterals, challenges the view that CAS per se leads to cognitive impairment.

Early adolescent cognitive gains are marked by increased sleep EEG coherence

Although the increases in cognitive capacities of adolescent humans are concurrent with significant cortical restructuring, functional associations between these phenomena are unclear. We examined the association between cortical development, as measured by the sleep EEG, and cognitive performance in a sample of 9/10 year olds followed up 1 to 3 years later. Our cognitive measures included a response inhibition task (Stroop), an executive control task (Trail Making), and a verbal fluency task (FAS). We correlated sleep EEG measures of power and intra-hemispheric coherence at the initial assessment with performance at that assessment. In addition we correlated the rate of change across assessments in sleep EEG measures with the rate of change in performance. We found no correlation between sleep EEG power and performance on cognitive tasks for the initial assessment. In contrast, we found a significant correlation of the rate of change in intra-hemispheric coherence for the sigma band (11 to 16 Hz) with rate of change in performance on the Stroop (r = 0.61; p<0.02) and Trail Making (r =  -0.51; p<0.02) but no association for the FAS. Thus, plastic changes in connectivity (i.e., sleep EEG coherence) were associated with improvement in complex cognitive function.

Cognitive and physiological effects of an acute physical activity intervention in elementary school children

The aim of the present study was to investigate the effects of an acute physical activity intervention that included cognitive engagement on executive functions and on cortisol level in young elementary school children. Half of the 104 participating children (6–8 years old) attended a 20-min sport sequence, which included cognitively engaging and playful forms of physical activity. The other half was assigned to a resting control condition. Individual differences in children's updating, inhibition, and shifting performance as well as salivary cortisol were assessed before (pre-test), immediately after (post-test), and 40 min after (follow-up) the intervention or control condition, respectively. Results revealed a significantly stronger improvement in inhibition in the experimental group compared to the control group, while it appeared that acute physical activity had no specific effect on updating and shifting. The intervention effect on inhibition leveled out 40 min after physical activity. Salivary cortisol increased significantly more in the experimental compared to the control group between post-test and follow-up and results support partly the assumed inverted U-shaped relationship between cortisol level and cognitive performance. In conclusion, results indicate that acute physical activity that includes cognitive engagement may have immediate positive effects on inhibition, but not necessarily on updating and shifting in elementary school children. This positive effect may partly be explained through cortisol elevation after acute physical activity.

Factors affecting cognitive outcome in early pediatric stroke

OBJECTIVE We examined cognitive performance in children after stroke to study the influence of age at stroke, seizures, lesion characteristics, neurologic impairment (NI), and functional outcome on cognitive outcome. METHODS This was a prospectively designed study conducted in 99 children who sustained an arterial ischemic stroke (AIS) between the age of 1 month and 16 years. All children underwent cognitive and neurologic follow-up examination sessions 2 years after the insult. Cognitive development was assessed with age-appropriate instruments. RESULTS Although mean cognitive performance was in the lower normative range, we found poorer results in subtests measuring visuoconstructive skills, short-term memory, and processing speed. Risk factors for negative cognitive outcome were young age at stroke, seizures, combined lesion location (cortical and subcortical), as well as marked NI. CONCLUSIONS We recommend that all children with a history of AIS undergo regularly scheduled neuropsychological assessment to ensure implementation of appropriate interventions and environmental adjustments as early as possible.

Cognitive remediation therapy: Does it generalize to significant outcome areas?

Objective: Cognitive remediation therapy (CRT) approaches have demonstrated to be effective in improving cognitive functions in schizophrenia. However, there is a lack of integrated CR approaches that target multiple neuro- and social-cognitive domains with a special focus on the generalization of therapy effects to functional outcome and negative symptoms. Method: This 8-site randomized controlled trial evaluated the efficacy of a novel cognitive-behavioral group therapy approach called integrated neurocognitive therapy (INT). INT includes manual-based exercises to improve all neuro- and social-cognitive domains as defined by the Measurement And Treatment Research to Improve Cognition in Schizophrenia (MATRICS) initiative by compensation and restitution. One hundred and fifty-six outpatients with a diagnosis of schizophrenia or schizoaffective disorder accord- ing to DSM-IV-TR were randomly assigned to receive 15 weeks of INT or treatment as usual (TAU). INT patients received 30 bi-weekly therapy sessions. Each session lasted 90min. Mixed models were applied to assess changes in neurocognition, social cognition, symptoms, and functional outcome at post-treatment and at 9-month follow-up. Results: Compared to TAU, INT patients showed significant improvements on multiple neuro- and social-cognitive domains, negative symptoms, and functional outcome after therapy and at 9-month follow-up. Number-needed-to-treat analyses indicate that only five INT patients are necessary to produce durable and meaningful improvements in functional outcome. Conclusions: Integrated interventions on neurocognition and social cognition have the potential to improve not only cognitive performance but also functional outcome and negative symptoms. These findings are important as treatment guidelines for schizophrenia have criticized CRT for their poor generalization effects.

Cognitive improvement in patients with carotid stenosis is independent of treatment type

Treatment of carotid artery stenosis decreases the long-term risk of stroke and may enhance cerebral blood flow. It is therefore expected to have the potential to prevent cognitive decline or even improve cognition over the long-term. However, intervention itself can cause peri-interventional cerebral infarcts, possibly resulting in a decline of cognitive performance, at least for a short time. We investigated the long-term effects of three treatment methods on cognition and the emotional state one year after intervention. In this prospective observational cohort study, 58 patients with extracranial carotid artery stenosis (≥70%) underwent magnetic resonance imaging and assessment of cognition, mood and motor speed before carotid endarterectomy (n = 20), carotid stenting (n = 10) or best medical treatment (n = 28) (i.e., time-point 1 [TP1]), and at one-year follow-up (TP2). Gain scores, reflecting cognitive change after treatment, were built according to performance as (TP2 -TP1)/TP1. Independent of the treatment type, significant improvement in frontal lobe functions, visual memory and motor speed was found. Performance level, motor speed and mood at TP1 were negatively correlated with gain scores, with greater improvement in patients with low performance before treatment. Active therapy, whether conservative or interventional, produces significant improvement of frontal lobe functions and memory in patients with carotid artery disease, independent of treatment type. This effect was particularly pronounced in patients with low cognitive performance prior to treatment.

Cognitive rehabilitation of working memory in juvenile multiple sclerosis-effects on cognitive functioning, functional MRI and network related connectivity.

PURPOSE To assess possible effects of working memory (WM) training on cognitive functionality, functional MRI and brain connectivity in patients with juvenile MS. METHODS Cognitive status, fMRI and inter-network connectivity were assessed in 5 cases with juvenile MS aged between 12 and 18 years. Afterwards they received a computerized WM training for four weeks. Primary cognitive outcome measures were WM (visual and verbal) and alertness. Activation patterns related to WM were assessed during fMRI using an N-Back task with increasing difficulty. Inter-network connectivity analyses were focused on fronto-parietal (left and right), default-mode (dorsal and ventral) and the anterior salience network. Cognitive functioning, fMRI and inter-network connectivity were reassessed directly after the training and again nine months following training. RESULTS Response to treatment was seen in two patients. These patients showed increased performance in WM and alertness after the training. These behavioural changes were accompanied by increased WM network activation and systematic changes in inter-network connectivity. The remaining participants were non-responders to treatment. Effects on cognitive performance were maintained up to nine months after training, whereas effects observed by fMRI disappeared. CONCLUSIONS Responders revealed training effects on all applied outcome measures. Disease activity and general intelligence may be factors associated with response to treatment.

Remission in schizophrenia: validity, frequency, predictors, and patients' perspective 5 years later

In March 2005, the Remission in Schizophrenia Working Group (RSWG) proposed a consensus definition of symptomatic remission in schizophrenia and developed specific operational criteria for its assessment. They pointed out, however, that the validity and the relationship to other outcome dimensions required further examination. This article reviews studies on the validity, frequency, and predictors of symptomatic remission in schizophrenia and studies on patients' perspectives. These studies have demonstrated that the RSWG remission criteria appear achievable and sustainable for a significant proportion of patients, and are related to a better overall symptomatic status and functional outcome and, to a less clear extent, to a better quality of life and cognitive performance. However, achieving symptomatic remission is not automatically concurrent with an adequate status in other outcome dimensions. The results of the present review suggest that the RSWG remission criteria are valid and useful. As such, they should be consistently applied in clinical trials. However the lack of consensus definitions of functional remission and adequate quality of life hampers research on their predictive validity on these outcome dimensions. Future research should therefore search for criteria of these dimensions and test whether the RSWG remission criteria consistently predict a "good" outcome with respect to functioning and quality of life.

Delirium upon admission to Swiss nursing homes

QUESTIONS UNDER STUDY: We wished to investigate the prevalence of delirium in patients upon admission to nursing homes and whether or not the previous place of residence predicts delirium. METHODS: The Resident Assessment Instrument Minimum Data Set (RAI-MDS) and the Nursing Home Confusion Assessment Method (NHCAM) were used to determine whether the previous place of residence (community, nursing home, acute care, psychiatric, rehabilitation hospital) predicted the prevalence of sub-syndromal or full delirium in nursing home residents in three Swiss cantons (n = 11745). RESULTS: 39.7% had sub-syndromal and 6.5% had full delirium. Lower cognitive performance and increased depressive symptoms were significant predictors of higher NHCAM values independent of previous residence. Age, civil status, continence, newly introduced drugs, and basic activities of daily living were predictors in some resident groups. The variance of NHCAM scores explained varied between 25.1% and 32.3% depending on previous residence. CONCLUSIONS: Sub-syndromal and full delirium are common upon nursing home admission. Increased dependence and depression are consistently associated with higher NHCAM scores. Patients from psychiatric settings have an increased risk of delirium. Although factors associated with delirium depend on a patient's previous residence, all patients must be carefully screened for sub-syndromal and full delirium.

Age-modulated association between prefrontal NAA and the BDNF gene

Brain-derived neurotrophic factor (BDNF) has been implicated in the pathophysiology of psychiatric and neurological disorders and in the mechanisms of antidepressant pharmacotherapy. Psychiatric and neurological conditions have also been associated with reduced brain levels of N-acetyl-aspartate (NAA), which has been used as a putative marker of neural integrity. However, few studies have explored the relationship between BDNF polymorphisms and NAA levels directly. Here, we present data from a single-voxel proton magnetic resonance spectroscopy study of 64 individuals and explore the relationship between BDNF polymorphisms and prefrontal NAA level. Our results indicate an association between a single nucleotide polymorphism (SNP) within BDNF, known as rs1519480, and reduced NAA level (p = 0.023). NAA levels were further predicted by age and Asian ancestry. There was a significant rs1519480 × age interaction on NAA level (p = 0.031). Specifically, the effect of rs1519480 on NAA level became significant at age ⩾34.17 yr. NAA level decreased with advancing age for genotype TT (p = 0.001) but not for genotype CT (p = 0.82) or CC (p = 0.34). Additional in silico analysis of 142 post-mortem brain samples revealed an association between the same SNP and reduced BDNF mRNA expression in the prefrontal cortex. The rs1519480 SNP influences BDNF mRNA expression and has an impact on prefrontal NAA level over time. This genetic mechanism may contribute to inter-individual variation in cognitive performance seen during normal ageing, as well as contributing to the risk for developing psychiatric and neurological conditions.

Intellectual outcome, motor skills and BMI of children with congenital hypothyroidism: a population-based study

AIM: To evaluate intellectual outcome, motor skills and anthropometric data of children with congenital hypothyroidism (CH). METHODS: Children with permanent CH who were born in 1999 in Bavaria were eligible for this prospective, population-based study. Cognitive performance was evaluated by the Kaufman Assessment Battery for Children and motor skills were assessed by the motor test, Motoriktest für vier-bis sechsjahrige Kinder (MOT) 4-6. RESULTS: Eighteen of 21 eligible children participated (86%). Median age of the children was 5.5 years (range 4.9-5.8). Treatment with levothyroxine was started after a median of 7.2 days (range 4-15) with a median dose of 12.0 microg/kg (range 7.2-17.0). Mean intelligence quotient (IQ) of the children was 100.4 (standard deviation [SD] 10.1): no children had IQ values below the normal range. Reactivity and speed of movement were significantly reduced in children with CH. Children with an initial thyroid-stimulating hormone (TSH) value of >200 mU/L performed significantly worse than children with TSH value of

Semantic Representation of Synaesthesia

Synaesthesia has multifaceted consequences for both subjective experience and cognitive performance. Here, I broach the issue of how synaesthesia is represented in semantic memory. I hypothesize that, for example, in grapheme colour synaesthesia, colour is represented as an additional feature in the semantic network that enables the formation of associations that are not present in non-synaesthetes. Thus, synaesthesia provokes richer memory representations which enable learning opportunities that are not present in non-synaesthetes, provides additional memory cues, and may trigger creative ideas.