Robert Krikorian

Tower of london procedure: A standard method and developmental data

The Tower of London procedure (TOL) is being utilized increasingly in clinical and experimental contexts, although there is considerable variation in how it is administered and scored. The procedure detailed here was developed using Shallices original problems and, along with the Porteus Maze Test (PMT), was administered to 205 elementary school students and 74 young adults. TOL scores increased with age in a linear fashion, and the performance of the sixth, seventh, and eighth grade subjects were not statistically different from the young adults. The TOL was moderately correlated with the PMT suggesting that these procedures share a planning component. These data provide initial developmental standards, and the materials, administration, and scoring procedures documented here provide a standard method for utilization of this instrument.

Blueberry Supplementation Improves Memory in Older Adults

The prevalence of dementia is increasing with expansion of the older adult population. In the absence of effective therapy, preventive approaches are essential to address this public health problem. Blueberries contain polyphenolic compounds, most prominently anthocyanins, which have antioxidant and anti-inflammatory effects. In addition, anthocyanins have been associated with increased neuronal signaling in brain centers, mediating memory function as well as improved glucose disposal, benefits that would be expected to mitigate neurodegeneration. This study investigated the effects of daily consumption of wild blueberry juice in a sample of nine older adults with early memory changes. At 12 weeks, improved paired associate learning (p = 0.009) and word list recall (p = 0.04) were observed. In addition, there were trends suggesting reduced depressive symptoms (p = 0.08) and lower glucose levels (p = 0.10). We also compared the memory performances of the blueberry subjects with a demographically matched sample who consumed a berry placebo beverage in a companion trial of identical design and observed comparable results for paired associate learning. The findings of this preliminary study suggest that moderate-term blueberry supplementation can confer neurocognitive benefit and establish a basis for more comprehensive human trials to study preventive potential and neuronal mechanisms.

Concord grape juice supplementation improves memory function in older adults with mild cognitive impairment

Concord grape juice contains polyphenol compounds, which have antioxidant and anti-inflammatory properties and influence neuronal signalling. Concord grape juice supplementation has been shown to reduce inflammation, blood pressure and vascular pathology in individuals with CVD, and consumption of such flavonoid-containing foods is associated with a reduced risk for dementia. In addition, preliminary animal data have indicated improvement in memory and motor function with grape juice supplementation, suggesting potential for cognitive benefit in ageing humans. In this initial investigation of neurocognitive effects, we enrolled twelve older adults with memory decline but not dementia in a randomised, placebo-controlled, double-blind trial with Concord grape juice supplementation for 12 weeks. We observed significant improvement in a measure of verbal learning and non-significant enhancement of verbal and spatial recall. There was no appreciable effect of the intervention on depressive symptoms and no effect on weight or waist circumference. A small increase in fasting insulin was observed for those consuming grape juice. These preliminary findings suggest that supplementation with Concord grape juice may enhance cognitive function for older adults with early memory decline and establish a basis for more comprehensive investigations to evaluate potential benefit and assess mechanisms of action.

Concord Grape Juice Supplementation and Neurocognitive Function in Human Aging

Polyphenol compounds found in berry fruits, in particular flavonoids, have been associated with health benefits including improvement in cognition and neuronal function with aging. Concord grape juice contains polyphenols, including anthocyanins and flavanols, and previous research has shown improvement in a number of human health conditions with grape juice supplementation. In the current study, older adult subjects with mild cognitive impairment consumed Concord grape juice or placebo for 16 weeks and were administered assessments of memory function and brain activation pre- and postintervention. Participants who consumed grape juice showed reduced semantic interference on memory tasks. Relatively greater activation in anterior and posterior regions of the right hemisphere was also observed with functional magnetic resonance imaging in the grape juice treated subjects. These findings provide further evidence that Concord grape juice can enhance neurocognitive function in older adults with mild memory decline.

Dietary ketosis enhances memory in mild cognitive impairment

We randomly assigned 23 older adults with mild cognitive impairment to either a high carbohydrate or very low carbohydrate diet. Following the 6-week intervention period, we observed improved verbal memory performance for the low carbohydrate subjects (p = 0.01) as well as reductions in weight (p < 0.0001), waist circumference (p < 0.0001), fasting glucose (p = 0.009), and fasting insulin (p = 0.005). Level of depressive symptoms was not affected. Change in calorie intake, insulin level, and weight were not correlated with memory performance for the entire sample, although a trend toward a moderate relationship between insulin and memory was observed within the low carbohydrate group. Ketone levels were positively correlated with memory performance (p = 0.04). These findings indicate that very low carbohydrate consumption, even in the short term, can improve memory function in older adults with increased risk for Alzheimers disease. While this effect may be attributable in part to correction of hyperinsulinemia, other mechanisms associated with ketosis such as reduced inflammation and enhanced energy metabolism also may have contributed to improved neurocognitive function. Further investigation of this intervention is warranted to evaluate its preventive potential and mechanisms of action in the context of early neurodegeneration.

Developmental Normative Data for the Corsi Block-Tapping Task

The Corsi Block-Tapping task has been utilized as a measure of spatial memory in both clinical and research contexts for several decades. Despite its wide application, the task has been employed with extraordinary variability in administration and scoring and in the composition of stimulus item sets. We have generated a set of test items containing quasi-randomly derived block-tapping sequences. In another study, we investigated item difficulty as a function of path configuration and showed a decline in performance with increasing span capacity load. In the current cross-sectional study, we evaluated developmental differences in span capacity by measuring performances of school children from grade 1 (M age = 7 years) to grade 8 (M age = 14) and a young adult sample (M age = 21 years). Mean span capacity increased incrementally and linearly with age, and no gender difference was observed. The increase in performance with advancing age supports the notion that spatial immediate memory capacity increases with maturation throughout childhood. Comparisons indicated that the span capacity of eighth graders (M = 6.9) was not statistically different from that of the young adults (M = 7.1), suggesting an upper developmental plateau for spatial span in early adolescence. This study provides a normative database for this widely utilized measure of spatial memory. Some of the data contained in this paper were presented at the meeting of the International Neuropsychological Society, Honolulu, February 2003.

Working memory and inhibitory control among manic and euthymic patients with bipolar disorder

Bipolar disorder (BPD) is a severe psychiatric illness that is characterized by episodes of extreme mood states. The affective components of bipolar disorder have been studied extensively, but only recently have investigators begun to systematically examine its cognitive concomitants. Although executive dysfunction has been reported in this population, especially while patients are manic, the tasks administered in many previous studies have made it difficult to determine the specific executive abilities that were compromised. The present study examined 15 patients with bipolar disorder who were manic, 18 who were euthymic, and 18 healthy participants. Tests were selected to evaluate two specific aspects of executive functioning in these participants. The Object Alternation Task was given as a measure of inhibitory control, and the Delayed Response Task was included as a measure of spatial delayed working memory. All groups performed similarly on the Delayed Response Task. On the Object Alternation Task, however, the manic and euthymic patients committed significantly more perseverative errors than healthy participants. These results indicated that patients in the present sample had relatively normal working memory abilities, but had a deficit in behavioral self-regulation, which was evident across mood states.

Corsi Block-Tapping task performance as a function of path configuration

The Corsi Block-Tapping (CB) task has been used as a measure of spatial memory since its development in 1971. However, a standard set of items has not been developed for this task, and inconsistencies in performances within levels have been demonstrated in association with different path configurations. This study investigated item consistency by analyzing the performances of 94 young adult participants on a block-tapping task that involved five quasi-randomly determined sequences at each of nine levels of difficulty. In general, performance declined with increasing path length. Cochran Q-test comparisons were conducted on the items within each level, and differential performances were identified at levels 7 and 8 only. Pairwise comparisons determined the specific items for which performance was discrepant, and further analysis indicated that performance decrements were related to more complicated block-tapping paths. The findings suggest that this version of the CB task is relatively consistent overall, and the observed effect of path configuration indirectly corroborates the spatial nature of this task. Performance heterogeneity at higher levels reflected more complicated path configuration and, presumably, greater span capacity load. Differential intra-level item consistency should be considered in clinical applications of spatial (configural) memory tasks in order to avoid erroneous interpretations concerning sustained attention ability based on failures within levels. Some of the data contained in this paper were presented at the meeting of the International Neuropsychological Society, Honolulu, February 2003.

Improved cognitive-cerebral function in older adults with chromium supplementation.

Abstract Insulin resistance is implicated in the pathophysiological changes associated with Alzheimers disease, and pharmaceutical treatments that overcome insulin resistance improve memory function in subjects with mild cognitive impairment (MCI) and early Alzheimers disease. Chromium (Cr) supplementation improves glucose disposal in patients with insulin resistance and diabetes. We sought to assess whether supplementation with Cr might improve memory and neural function in older adults with cognitive decline. In a placebo-controlled, double-blind trial, we randomly assigned 26 older adults to receive either chromium picolinate (CrPic) or placebo for 12 weeks. Memory and depression were assessed prior to treatment initiation and during the final week of treatment. We also performed functional magnetic resonance imaging (fMRI) scans on a subset of subjects. Although learning rate and retention were not enhanced by CrPic supplementation, we observed reduced semantic interference on learning, recall, and recognition memory tasks. In addition, fMRI indicated comparatively increased activation for the CrPic subjects in right thalamic, right temporal, right posterior parietal, and bifrontal regions. These findings suggest that supplementation with CrPic can enhance cognitive inhibitory control and cerebral function in older adults at risk for neurodegeneration.

Inhibitory control in Obsessive-Compulsive Disorder

The clinical features of Obsessive-Compulsive Disorder (OCD) suggest that a fundamental deficit of inhibitory control is intrinsic to the disorder. In this preliminary study, we sought to examine cognitive disinhibition in OCD by using an established laboratory technique. The stop signal task was administered to a higher functioning, untreated group of individuals with OCD, and to healthy comparison participants. Surprisingly, the OCD participants exhibited more accurate performance, suggesting better inhibitory control on this task. This unexpected finding suggests that higher functioning individuals with OCD are capable of adequate inhibition in certain contexts. It was speculated, however, that emotional stimulation might negatively affect performance and that this might be studied in subsequent research.