Non-alcoholic fatty liver disease is associated with insulin resistance and dyslipidaemia and can progress to steatohepatitis and cirrhosis. We sought to determine whether dietary fat and saturated fat content alter liver fat in the absence of weight change in an older population. Liver fat was quantified by magnetic resonance spectroscopy before and after 4 weeks on an isoenergetic low-fat/low-saturated fat/low-glycaemic index (LGI) (LSAT: 23 % fat/7 % saturated fat/GI < 55) or a high-fat/high-saturated fat/high-GI (HSAT: 43 % fat/24 % saturated fat/GI>70) diet in older subjects. In the present study, twenty subjects (seven males/thirteen females; age 69·3 (sem 1·6) years, BMI 26·9 (sem 0·8) kg/m2) were randomised to the LSAT diet and fifteen subjects (six males/nine females; age 68·6 (sem 1·8) years, BMI 28·1 (sem 0·9) kg/m2) to the HSAT diet. Weight remained stable. Liver fat decreased significantly on the LSAT diet (median 2·2 (interquartile range (IQR) 3·1) to 1·7 (IQR 1·8) %, P= 0·002) but did not change on the HSAT diet (median 1·2 (IQR 4·1) to 1·6 (IQR 3·9) %). The LSAT diet lowered fasting glucose and total cholesterol, HDL-cholesterol and LDL-cholesterol and raised TAG (P< 0·05), while the HSAT diet had no effect on glucose or HDL-cholesterol but increased total cholesterol and LDL-cholesterol (P< 0·05). Fasting insulin and homeostasis model of insulin resistance did not change significantly on either diet, but the Matsuda index of insulin sensitivity improved on the LSAT diet (P< 0·05). Assignment to the LSAT v. HSAT diet was a predictor of changes in lipid parameters but not liver fat. We conclude that diet composition may be an important factor in the accumulation of liver fat, with a low-fat/low-saturated fat/LGI diet being beneficial.

It has been postulated that rehearsal rate is the primary determinant of working memory capacity for verbal material (Baddeley et al., 1975). A previous study of normal control children and children with spastic diplegic cerebral palsy (SDCP) suggested that covert rather than overt rehearsal rate determines working memory capacity (White et al., 1994). In the current study, a subset of SDCP children who received a surgical treatment to relieve spasticity were retested on measures of articulation rate and memory span. A subset of control children from the original study were also retested. The SDCP group showed improvements in articulation rate at follow-up, though memory span did not change and was again equivalent to that of controls. These findings indicate that increases in articulation rate are not necessarily accompanied by improvements in memory span, and provide additional evidence that working memory capacity may be determined by covert rather than overt articulatory rehearsal. (JINS, 1995, I, 49–55.)

ABSTRACT

Insulin and insulin resistance likely play a significant role in the pathophysiology and cognitive decline associated with Alzheimer's disease (AD). Insulin, insulin receptors, and insulin-sensitive glucose transporters are selectively localized the brain, including medial temporal areas that support memory. Raising brain insulin levels can facilitate memory and increase cerebrospinal fluid levels of β-amyloid (Aβ) and inflammatory markers. Insulin's effects on cognition may reflect normal regulation of glucose metabolism, long-term potentiation, and neurotransmitter levels. Consequently, insulin abnormalities may disrupt normal memory functioning and promote pathophysiological processes observed in patients with neurodegenerative disorders. Conversely, restoring normal insulin activity may exert a beneficial effect on pathophysiological processes. For example, peroxisome proliferator-activated receptor (PPAR)-gamma agonists (insulin sensitizing agents used to treat type 2 diabetes mellitus) modulate neuronal cell survival, inflammatory responses, mitochondrial functioning, and possibly Aβ processing and deposition. One PPAR-gamma agonist, rosiglitazone, facilitates memory and modulates plasma Aβ levels in patients with AD. Likewise, a healthy diet and regular exercise may improve insulin sensitivity and decrease the risk for both AD. Furthermore, intranasal insulin administration rapidly delivers insulin to the brain without altering plasma insulin or glucose levels. Studies to date suggest that this procedure can facilitate memory and modulate plasma Aβ levels in memory-impaired adults. Interestingly, the adverse effects of insulin abnormalities and the beneficial effects of improving insulin sensitivity may differ by apolipoprotein E (APOE) genotype, an established risk factor for AD. Patients who do carry lower doses of the APOE e4 allele have an enhanced risk for insulin abnormalities and are also more responsive to the memory enhancing effects of both rosiglitazone and intranasal insulin administration, relative to other patients. Therefore, future therapeutic trials should consider the moderating effects of APOE genotype.

The presence of cocaine during the prenatal period disrupts the development of neural systems involved in mediating visual attention; therefore, it is possible that prenatal cocaine exposure results in impairments in visual attention in early childhood. In the current study we hypothesized that preschool children with prenatal cocaine exposure would exhibit difficulties in the disengagement operation of visual attention and in sustaining attention, particularly for targets presented in the right visual field. Fourteen cocaine-exposed children and 20 control children between 14 and 60 months of age were assessed on measures of visual attention, cognition, and behavior. Cocaine-exposed children had slower reaction times on disengagement trials in the second half of our attention task, supporting our hypotheses that impairments in disengagement and sustained attention are associated with prenatal cocaine exposure. There was a trend for slower reaction times to targets presented in the right visual field, but not to targets presented in the left visual field. Cocaine-exposed children also exhibited greater difficulties in behavioral regulation. Overall, our findings suggest that children with prenatal cocaine exposure demonstrate specific impairments in visual attention and behavioral regulation. (JINS, 2002, 8, 12–21.)

Inhibition of return is a bias in attention that reduces the likelihood of returning attention to previously viewed locations. This attention bias develops during the first 6 months of life and is putatively mediated by midbrain structures. The present study evaluated the effects of perinatal lesions on the development of inhibition of return. Thirty-three children with perinatal injury resulting in spastic diplegic cerebral palsy were grouped based on magnetic resonance exams. Children with anterior (n = 5), posterior (n = 12), diffuse (n = 8), or no apparent (n = 8) lesions were compared with a group of age-matched children without neurologic injury (n = 39) on an orienting task designed to elicit inhibition of return. Short-delay trials demonstrated grossly intact facilitation of attention for all groups. Long-delay trials that produced inhibition of return in the control and posterior injury groups indicated a disruption of inhibition of return in the groups with anterior and diffuse lesions. The findings are consistent with previous reports that anterior regions are important for the developing attention system, and that bilateral injury can result in unilateral disruption of visual attention. (JINS, 2001, 7, 275–284.)

Associate learning for visual nonverbal and auditory verbal items was examined in 21 children with spastic diplegic cerebral palsy (SDCP) and 28 healthy children using four paired associate tasks. SDCP children showed poorer performance than the comparison group for learning pairs that required visual nonverbal responses, regardless of the stimulus modality. Within the SDCP group, lesion severity was assessed in 17 of the children. Lesion severity was related to the level of performance on paired associate tasks requiring visual nonverbal responses; lesion severity did not reach statistical significance for tasks requiring auditory verbal responses. The study suggests: (1) periventricular white matter regions are important for the development of basic learning processes, such as associative learning, and (2) learning of visual nonverbal material is disproportionately affected following white matter injury early in life. (JINS, 1997, 3, 521–527.)

Previous studies of the neuropsychological consequences of insulin dependent diabetes mellitus (IDDM) have had mixed and often contradictory results, possibly due to the heterogeneity of the samples and neuropsychological measures, and a lack of specific hypotheses. In order to address this problem, we focused on the effect of severe hypoglycemia on memory functioning in a relatively homogeneous sample of childhood-onset IDDM patients. Given the deleterious effects of hypoglycemia on medial temporal lobe structures (e.g., hippocampus) and the relationship between medial temporal damage and declarative memory functioning, we hypothesized that those patients who had experienced severe hypoglycemia would demonstrate impaired declarative memory and spared nondeclarative memory functioning. Results of the study were generally consistent with this hypothesis, although some impact of hypoglycemia was observed on perceptual priming ability. (JINS, 1997, 3, 509–520.)

Previous studies have reported that developmental disruption of dopaminergic systems results in lateralized deficits in visual attention (Posner et al., 1991; Craft et al., 1992). Infants who were prenatally exposed to cocaine were hypothesized to have increased reaction times to targets in the right visual field on measures of visual attention compared with infants who were not exposed to cocaine. Seventeen children without prenatal exposure to cocaine and 14 children who were exposed to cocaine (age range from 8–40 months) completed a visual attention task, the Mental Development Index of the Bayley Scales of Infant Development, Second Edition; and the Preschool Language Scale, Third Edition. Cocaine-exposed children were slower to orient to stimuli in the right visual field after repeated trials, especially after attention was first cued to the left visual field. They were also less likely to orient to the right when given a choice. Results suggest that the left hemisphere visual attention system is disproportionately affected by prenatal exposure to cocaine. (JINS, 1997, 3, 237–245.)