Partial agenesis of the corpus callosum, hippocampal atrophy, and stable intellectual disability associated with Roifman syndrome.

In 2006, we reported the cognitive and behavioral phenotype of the seventh case of Roifman syndrome (OMIM 300258). Aged 11 years 6 months, the patient displayed significant intellectual disability with proportionate impairments in attentional-executive, memory, and visuo-spatial abilities despite appearing socially "able." This discrepancy may be explained by good social-emotional skills masking his intellectual disability, by decline in cognitive abilities over time, or by unusual neuroradiological abnormalities not previously examined in Roifman syndrome. Here, we present results from a structural MRI scan, neurocognitive evaluations repeated 2 and 5 years post-baseline and assessments of face and emotional processing. The MRI revealed partial agenesis of the corpus callosum, bilateral hypoplastic hippocampi but bilaterally intact amygdala. No evidence was found for decline in the patient's neurocognitive profile. Emotional processing data indicated an age-appropriate pattern of reactivity to emotional stimuli and preserved facial identity recognition abilities, but impairments in recognition of negative facial expressions. The results confirmed a stable pattern of intellectual disability, and indicated that Roifman syndrome may be associated with major structural neuro-anatomical abnormalities. We suggest that the relative strengths in emotion and face processing are consistent with the patient's apparently able social behavior, and with intact amygdalar function.

Neuropsychological attention skills and related behaviours in adults with tuberous sclerosis complex.

Tuberous sclerosis complex (TSC) is a genetic disorder associated with mTOR over-activation and disruption of MAPK, PI3K and AMPK signalling. Children with TSC have significant deficits on neuropsychological attention tasks, particularly dual tasking. Here we investigated attentional skills and related behaviours in daily life in normally intelligent adults with TSC and matched controls using the Test of Everyday Attention for Children (TEA-Ch) and the Attention-Deficit Scales for Adults (ADSA). No group differences were demonstrated on selective or sustained attention tasks carried out alone. However, adults with TSC performed significantly worse when these tasks were combined in a cross-modal dual task condition. On the ADSA the TSC group had significantly worse scores on several subscales (attention/concentration, behaviour/disorganization, academic and emotional behaviours) compared to controls and these correlated with dual task performance, indicating a clear impact of dual task deficits on attention-related behaviours in daily life. The presence or absence of epilepsy did not influence dual task performance or attention-deficits in daily life. Taken together with similar findings in children, results suggest that dual task difficulties are a core feature of the neuropsychological phenotype of TSC.

Predicting outcome in mild cognitive impairment: 4-year follow-up study.

BACKGROUND: Cognitive impairment precedes the diagnosis of Alzheimer's disease. It is unclear which psychometric measures predict dementia, and what cut-off points should be used. Replicable cognitive measures to provide information about differential diagnosis and prognosis would be clinically useful. AIMS: In a prospective cohort study we investigated which measures distinguish between individuals with amnestic mild cognitive impairment (aMCI) that converts to dementia and those whose impairment does not, and which combination of measures best predicts the fate of people with aMCI. METHOD: Forty-four participants with aMCI underwent extensive neuropsychological assessment at baseline and annually thereafter for an average of 4 years. Differences in baseline cognitive performance of participants who were converters and non-converters to clinically diagnosed dementia were analysed. Classification accuracy was estimated by sensitivity, specificity, positive and negative predictive values and using logistic regression. RESULTS: Forty-one percent of participants had progressed to dementia by the end of study, with a mean annual conversion rate of 11%. Most (63%) showed persisting or progressive cognitive impairment, irrespective of diagnosis. The Addenbrooke's Cognitive Examination together with the discrimination index of the Hopkins Verbal Learning Test - Revised (but none of the demographic indices) differentiated the participants who were converters from the non-converters at baseline with 74% accuracy. CONCLUSIONS: Targeted neuropsychological assessment, beyond simple cognitive screening, could be used in clinical practice to provide individuals with aMCI with prognostic information and aid selective early initiation of monitoring and treatment among those who progress towards a clinically diagnosable dementia.

5-(123)I-A-85380 binding to the α4ß2-nicotinic receptor in mild cognitive impairment.

Treatments currently licensed for Alzheimer's dementia target cholinergic brain systems. In vivo nicotinic receptor binding may provide an early marker of illness and treatment suitability. In this pilot, we examined nine patients with amnestic mild cognitive impairment (MCI) and 10 age and education matched healthy volunteers with high resolution SPECT and the nicotinic receptor ligand 5-(123)I-A-85380. Uptake data were analysed using voxel-based techniques for group comparisons and regression analyses with cognitive impairment as covariates. MCI patients had discrete reductions in uptake in medial temporal cortex. Correlations with cognitive impairment were found in left temporo-parietal areas (Addenbrooke's Cognitive Examination) and bilateral temporo-limbic areas (Rey Auditory Verbal Learning Test), and right parahippocampal gyrus (Rey Complex Figure Test) within the patient group. In vivo nicotinic receptor binding appears to be sensitive to brain changes in MCI. Larger scale explorations of patients undergoing treatment will be necessary to evaluate its use in predicting or monitoring treatment response.

Lexical and semantic fluency discrepancy scores in aMCI and early Alzheimer's disease.

Episodic memory is compromised in amnestic mild cognitive impairment (aMCI), but lesser deficits in other cognitive domains are also commonly observed and may be helpful in identifying this group. The relative difference in performance on lexical and semantic fluency tasks may be a sensitive and specific measure in aMCI and early Alzheimer's disease (AD). We compared four groups of participants, 35 early AD, 47 aMCI, 24 healthy controls, and 18 depressive out-patient controls, on semantic and lexical fluency as well as other neuropsychological tests. Early AD and aMCI patients showed a distinct pattern of semantic impairment in the two fluency measures compared with the healthy and depressive controls. The findings implicate early failure of the semantic memory system in aMCI and AD and suggest that consideration of the discrepancy in performance on semantic and lexical fluency measures may help in the early identification of AD.

Screening for mild cognitive impairment: a systematic review.

OBJECTIVE: Patients with mild cognitive impairment account for a significant number of referrals to old age psychiatry services and specialist memory clinics. The cognitive evaluation of such patients is commonly restricted to brief dementia screens, with no consideration to their suitability for assessing MCI. Here, we review the utility of such cognitive screens for MCI and provide an overview of validated instruments. METHODS: We identified papers published after Petersen and colleagues 1999 MCI criteria (Petersen et al., 1999) and examining face-to-face cognitive screening for MCI from publication databases using combinations of the search terms 'mild cognitive impairment' and 'cognitive screening'. We also combined the former search with the names of 39 screening tests recently identified in a relevant review (Cullen et al., 2007). RESULTS: Fifteen cognitive screening instruments were identified, 11 cover a restricted range of cognitive domains. High sensitivity and specificity for MCI relative to healthy controls were reported for two comprehensive and two noncomprehensive screening instruments, adequate test-retest and inter-rater reliability for only one of these. With the exception of three studies, sample sizes were universally small (i.e. n