Elevated glucocorticoid levels produce hippocampal dysfunction and correlate with individual deficits in spatial learning in aged rats. Previously we related persistent cortisol increases to memory impairments in elderly humans studied over five years. Here we demonstrate that aged humans with significant prolonged cortisol elevations showed reduced hippocampal volume and deficits in hippocampus-dependent memory tasks compared to normal-cortisol controls. Moreover, the degree of hippocampal atrophy correlated strongly with both the degree of cortisol elevation over time and current basal cortisol levels. Therefore, basal cortisol elevation may cause hippocampal damage and impair hippocampus-dependent learning and memory in humans.

In the present study we introduce a sensitive video-based test for the evaluation of subtle mindreading difficulties: the Movie for the Assessment of Social Cognition (MASC). This new mindreading tool involves watching a short film and answering questions referring to the actors' mental states. A group of adults with Asperger syndrome (n = 19) and well-matched control subjects (n = 20) were administered the MASC and three other mindreading tools as part of a broader neuropsychological testing session. Compared to control subjects, Asperger individuals exhibited marked and selective difficulties in social cognition. A Receiver Operating Characteristic (ROC) analysis for the mindreading tests identified the MASC as discriminating the diagnostic groups most accurately. Issues pertaining to the multidimensionality of the social cognition construct are discussed.

Empathy is a multidimensional construct consisting of cognitive (inferring mental states) and emotional (empathic concern) components. Despite a paucity of research, individuals on the autism spectrum are generally believed to lack empathy. In the current study we used a new, photo-based measure, the Multifaceted Empathy Test (MET), to assess empathy multidimensionally in a group of 17 individuals with Asperger syndrome (AS) and 18 well-matched controls. Results suggested that while individuals with AS are impaired in cognitive empathy, they do not differ from controls in emotional empathy. Level of general emotional arousability and socially desirable answer tendencies did not differ between groups. Internal consistency of the MET's scales ranged from .71 to .92, and convergent and divergent validity were highly satisfactory.

Neuropathology studies show that patients with mild cognitive impairment (MCI) and Alzheimer's disease typically have lesions of the entorhinal cortex (EC), hippocampus (Hip), and temporal neocortex. Related observations with in vivo imaging have enabled the prediction of dementia from MCI. Although individuals with normal cognition may have focal EC lesions, this anatomy has not been studied as a predictor of cognitive decline and brain change. The objective of this MRI-guided 2-[ 18 F]fluoro-2-deoxy-D-glucose͞ positron-emission tomography (FDG͞PET) study was to examine the hypothesis that among normal elderly subjects, EC METglu reductions predict decline and the involvement of the Hip and neocortex. In a 3-year longitudinal study of 48 healthy normal elderly, 12 individuals (mean age 72) demonstrated cognitive decline (11 to MCI and 1 to Alzheimer's disease). Nondeclining controls were matched on apolipoprotein E genotype, age, education, and gender. At baseline, metabolic reductions in the EC accurately predicted the conversion from normal to MCI. Among those who declined, the baseline EC predicted longitudinal memory and temporal neocortex metabolic reductions. At follow-up, those who declined showed memory impairment and hypometabolism in temporal lobe neocortex and Hip. Among those subjects who declined, apolipoprotein E E4 carriers showed marked longitudinal temporal neocortex reductions. In summary, these data suggest that an EC stage of brain involvement can be detected in normal elderly that predicts future cognitive and brain metabolism reductions. Progressive E4-related hypometabolism may underlie the known increased susceptibility for dementia. Further study is required to estimate individual risks and to determine the physiologic basis for METglu changes detected while cognition is normal.W ith increasing age, there is an increased risk for memory impairment (1); however, the affected anatomy predicting future impairment has not been well characterized. Although many conditions result in memory loss, Alzheimer's disease (AD) may be the most common cause (2). Neuropathology studies of normal elderly and subjects with clinically recognizable mild cognitive impairments (MCI) show that both the entorhinal cortex (EC) and hippocampus (Hip), structures important for memory function, are particularly vulnerable to neurofibrillary tangle (NFT) pathology (3, 4) and neuronal loss (5). Braak and Braak (3) proposed a staging model for brain AD where the NFT distribution expands from an EC locus to involve the Hip and then the neocortex. Carriers of an apolipoprotein E (apoE) E4 allele show at younger ages increased neocortical beta amyloid deposits (6) and EC NFTs (7). These changes may contribute to their increased risk for AD.In vivo, little is known of the regional anatomical changes marking the transitions between normal cognition and dementia. Although cross-sectional MRI and positron-emission tomography (PET) studies support an in vivo adaptation of the Braak staging model (8, 9), longitudinal imaging s...

Aims/hypothesis There is evidence that type 2 diabetes mellitus is associated with cognitive impairment. Most studies investigating this association have evaluated elderly individuals, after many years of diabetes, who generally have poor glycaemic control and significant vascular disease. The aim of the current study was to investigate the early cognitive consequences and associated brain correlates of type 2 diabetes. Materials and methods With regard to cognition and brain measures, we compared 23 age-, sex-and educationmatched control subjects with 23 mostly middle-aged individuals with relatively well-controlled diabetes of less than 10 years from the time of diagnosis. Results We found deficits in hippocampal-based memory performance and preservation of other cognitive domains. Relative to control subjects, individuals with diabetes had reductions in brain volumes that were restricted to the hippocampus. There was an inverse relationship between glycaemic control and hippocampal volume; in multivariate regression analysis, HbA 1c was the only significant predictor of hippocampal volume, accounting for 33% of the observed variance. Other variables commonly associated with type 2 diabetes, such as elevated BMI, hypertension or dyslipidaemia, did not independently contribute to the variance in hippocampal volume. Conclusions/interpretation These results suggest that the medial temporal lobe may be the first brain site affected by type 2 diabetes and that individuals in poorer metabolic control may be affected to a greater extent.

In adults, obesity has been associated with disinhibited eating, decreased cortical gray matter volume, and lower performance on cognitive assessments. Much less is known about these relationships in adolescence and there are no studies assessing behavioral, cognitive, and neurostructural measures in the same group of study participants. This study examined the relationship between obesity, executive function, disinhibition, and brain volumes in relatively healthy youth. Participants included 54 obese and 37 lean adolescents. Participants received a cognitive battery, questionnaires of eating behaviors, and magnetic resonance imaging (MRI). Neuropsychological assessments included tasks targeting frontal lobe function. Eating behaviors were determined using the Three Factor Eating Questionnaire (TFEQ), and structural MRIs were performed on a 1.5 T Siemens Avanto MRI System (Siemens, Erlangen, Germany) to determine brain gray matter volumes. Lean and obese adolescents were matched on age, years of education, gender, and socioeconomic status. Relative to lean adolescents, obese participants had significantly higher ratings of disinhibition on the TFEQ, lower performance on the cognitive tests, and lower orbitofrontal cortex volume. Disinhibition significantly correlated with Body Mass Index, Stroop Color-Word score, and orbitofrontal cortex volume. This is the first report of these associations in adolescents and point to the importance of better understanding the associations between neurostructural deficits and obesity.

Metabolic Syndrome (MetS), a clustering of risk factors for type 2 diabetes mellitus and cardiovascular disease, has been associated with cognitive dysfunction and brain abnormalities. This review describes the literature on the impact of MetS on brain and cognition and suggests directions for future research. A literature search for reports of MetS and cognition and brain imaging was conducted for both non-elderly adults and adolescents. No studies were found describing MetS and brain or cognition among adolescents; therefore we also included studies investigating individual components of MetS in this age group. Most studies found associations between MetS and cognitive dysfunction. Multiple cognitive domains were affected by MetS in adults. In adolescents, the majority of findings were in executive functioning. Brain imaging literature in adults implicated MetS in ischemic stroke, white matter alterations and altered brain metabolism. For adolescents, individual MetS factors were linked to volume losses in the hippocampus and frontal lobes. MetS negatively impacts cognitive performance and brain structure. Potential explanatory models include impaired vascular reactivity, neuroinflammation, oxidative stress, and abnormal brain lipid metabolism. We posit that insulin resistance-associated impairment in cerebrovascular reactivity is an important mechanism underlying brain deficits seen in MetS.

A deficit in empathy has consistently been cited as a central characteristic of Asperger syndrome (AS), but previous research on adults has predominantly focused on cognitive empathy, effectively ignoring the role of affective empathy. We administered the Interpersonal Reactivity Index (IRI), a multi-dimensional measure of empathy, and the Strange Stories test to 21 adults with AS and 21 matched controls. Our data show that while the AS group scored lower on the measures of cognitive empathy and theory of mind, they were no different from controls on one affective empathy scale of the IRI (empathic concern), and scored higher than controls on the other (personal distress). Therefore, we propose that the issue of empathy in AS should be revisited.