40-Hz steady state response in Alzheimer's disease and mild cognitive impairment.

The 40-Hz steady state response (SSR) reflects early sensory processing and can be measured with electroencephalography (EEG). The current study compared the 40-Hz SSR in groups consisting of mild Alzheimer's disease patients (AD) (n=15), subjects with mild cognitive impairment (MCI) (n=20) and healthy elderly control subjects (n=20). All participants were naïve for psychoactive drugs. Auditory click trains at a frequency of 40-Hz evoked the 40-Hz SSR. To evaluate test-retest reliability (TRR), subjects underwent a similar assessment 1 week after the first. The results showed a high TRR and a significant increase of 40-Hz SSR power in the AD group compared to MCI and controls. Furthermore a moderate correlation between 40-Hz SSR power and cognitive performance as measured by ADAS-cog was shown. The results suggest that 40-Hz SSR might be an interesting candidate marker of disease progression.

Memory impairments in humans after acute tryptophan depletion using a novel gelatin-based protein drink.

Acute tryptophan depletion (ATD) can be used to decrease serotonin levels in the brain. Traditionally, ATD has been established by administering amino acid (AA) mixtures and studies using this method showed that serotonin is involved in learning and memory processes. This study used a recently developed gelatin-based protein drink to examine whether it 1) is superior to the traditional AA method in controlling the tryptophan levels in the placebo condition, 2) impairs long-term memory and 3) differentially affects episodic and spatial memory. Sixteen healthy subjects participated in a double-blind, placebo-controlled study. Memory was assessed using a visual verbal learning test and an object relocation task (spatial memory). Tryptophan ratio significantly decreased after ATD and did not significantly increase in the placebo condition. Delayed recall in the verbal learning test and delayed relocation of objects to positions in the spatial task were impaired after ATD. Spatial short-term memory, however, improved. The current results indicate that the tryptophan levels were essentially neutral in the placebo condition compared with those in the traditional AA mixture. Our study provides further evidence that impairment in long-term episodic and elementary spatial memory after ATD is related to lowered tryptophan levels in plasma.

Increased EEG gamma band activity in Alzheimer's disease and mild cognitive impairment.

High frequency (30-70 Hz) gamma band oscillations in the human electro-encephalogram (EEG) are thought to reflect perceptual and cognitive processes. It is therefore interesting to study these measures in cognitive impairment and dementia. To evaluate gamma band oscillations as a diagnostic biomarker in Alzheimer's disease (AD) and mild cognitive impairment (MCI), 15 psychoactive drug naïve AD patients, 20 MCI patients and 20 healthy controls participated in this study. Gamma band power (GBP) was measured in four conditions viz. resting state, music listening, story listening and visual stimulation. To evaluate test-retest reliability (TRR), subjects underwent a similar assessment one week after the first. The overall TRR was high. Elevated GBP was observed in AD when compared to MCI and control subjects in all conditions. The results suggest that elevated GBP is a reproducible and sensitive measure for cognitive dysfunction in AD in comparison with MCI and controls.

Lower high-density lipoprotein cholesterol and increased omega-6 polyunsaturated fatty acids in first-degree relatives of bipolar patients.

BACKGROUND: Lower serum high-density lipoprotein cholesterol and increased ratio of omega-6/omega-3 fatty acids have been reported in unipolar and bipolar depressed patients. Changes in cholesterol and fatty acids have been suggested to affect membrane viscosity and consequently serotonergic neurotransmitter expression. The goal of this study was to investigate whether lower baseline cholesterol and increased omega-6 and lower omega-3 fatty acids are present in healthy first-degree relatives of bipolar patients compared with controls and whether these changes were associated with neuroendocrine responses to an i.v. tryptophan challenge or mood. METHOD: Baseline cholesterol, fatty acids and mood were determined in healthy first-degree relatives of patients with bipolar disorders (N = 30) and healthy matched controls (N = 15) (parallel-group design). Prolactin and cortisol were measured following tryptophan infusion. RESULTS: First-degree relatives showed significantly lower plasma high-density lipoprotein cholesterol and increased total omega-6 fatty acids in phospholipids. Lower total omega-3 and higher total omega-6 fatty acids in phospholipids were positively correlated with peak prolactin response to tryptophan. Lower total omega-3 fatty acids in phospholipids and cholesteryl esters were associated with lower mood. CONCLUSIONS: Abnormalities of lower plasma high-density lipoprotein cholesterol and increased total omega-6 fatty acids in phospholipids in these subjects are in agreement with findings in bipolar and major depressed patients. Changes in fatty acids show an association with central serotonergic parameters. It is suggested that these abnormalities in cholesterol and fatty acids may constitute a trait marker for bipolar disorders.

Safety of soy-derived phosphatidylserine in elderly people.

Phosphatidylserine (PS) is a phospholipid which has been claimed to enhance neuronal membrane function, and can be derived from several sources. Earlier studies used brain cortex derived PS, of which the human tolerability of 300mg daily in 130 patients has been shown. The human tolerability of PS derived from soybean has not been reported, although it is widely sold as a nutritional supplement which may improve cognitive function in the elderly. We report the results of a study of the safety of two dosages of soy-phosphatidylserine (S-PS) in elderly. Subjects were 120 elderly of both sexes who fulfilled the more stringent criteria for age-associated memory impairment; some also fulfilled the criteria for age-associated cognitive decline. Subjects were allocated at random to one of the three treatment groups: placebo, 300 or 600 mg S-PS daily. Standard biochemical and hematological safety parameters, blood pressure, heart rate and adverse events were assessed at baseline, after 6 and 12 weeks of treatment. No significant differences were found in any of the outcome variables between the treatment groups after Bonferonni-Holme correction. In conclusion, soy derived PS is a safe nutritional supplement for older persons if taken up to a dosage of 200 mg three times daily.

Cognition following acute tryptophan depletion: difference between first-degree relatives of bipolar disorder patients and matched healthy control volunteers.

BACKGROUND: Serotonergic circuits have been proposed to mediate cognitive processes, particularly learning and memory. Cognitive impairment is often seen in bipolar disorders in relation to a possible lowered serotonergic turnover. METHODS: We investigated the effects of acute tryptophan depletion (ATD) on cognitive performance in healthy first-degree relatives of bipolar patients (FH) (N= 30) and matched controls (N= 15) in a placebo-controlled, double-blind cross-over design. Performance on planning, memory and attention tasks were assessed at baseline and 5 h after ATD. RESULTS: Following ATD, speed of information processing on the planning task was impaired in the FH group but not in the control group. FH subjects with a bipolar disorder type I relative (FH I) showed impairments in planning and memory, independent of ATD. In all subjects, ATD impaired long-term memory performance and speed of information processing. ATD did not affect short-term memory and focused and divided attention. CONCLUSIONS: The results suggest serotonergic vulnerability affecting frontal lobe areas in FH subjects, indicated by impaired planning. Biological vulnerability in FH I subjects is reflected in impaired planning and memory performance. In conclusion, the cognitive dysfunctions in FH subjects indicate an endophenotype constituting a possible biological marker in bipolar psychopathology. Serotonin appears to be involved in speed of information processing, verbal and visual memory and learning processes.

The influence of soy-derived phosphatidylserine on cognition in age-associated memory impairment.

Phosphatidylserine (PS) is a phospholipid widely sold as a nutritional supplement. PS has been claimed to enhance neuronal membrane function and hence cognitive function, especially in the elderly. We report the results of a clinical trial of soybean-derived PS (S-PS) in aging subjects with memory complaints. Subjects were 120 elderly (> 57 years) of both sexes who fulfilled the more stringent criteria for age-associated memory impairment (AAMI); some also fulfilled the criteria for age-associated cognitive decline. Subjects were allocated at random to one of the three treatment groups: placebo, 300mg S-PS daily, or 600mg S-PS daily. Assessments were carried out at baseline, after 6 and 12 weeks of treatment, and after a wash-out period of 3 weeks. Tests of learning and memory, choice reaction time, planning and attentional functions were administered at each assessment. Delayed recall and recognition of a previously learned word list comprised the primary outcome measures. No significant differences were found in any of the outcome variables between the treatment groups. There were also no significant interactions between treatment and 'severity of memory complaints'. In conclusion, a daily supplement of S-PS does not affect memory or other cognitive functions in older individuals with memory complaints.

Nutrients, age and cognitive function.

Many nutrients or indices of nutritional status are associated with cognitive functioning, although the size of the effects on cognitive performance may be small. Results from recent studies, however, seem consistently to indicate that supplementation with beta-carotene and alpha-tocopherol, substances that promote antioxidant vitamins A and E, respectively, can be beneficial to cognitive function in elderly people. Folate rather than vitamin B12 appears to be associated with cognitive functioning. Furthermore the daily intake of ginkgo biloba extract can enhance cognitive performance and has been proved to delay cognitive decline in dementia. A proper dietary composition with regard to the ratio of carbohydrates to proteins, as well as the inclusion of sufficient micronutrients, seems to be favourable in the maintenance of cognitive function in the elderly. Glucose can enhance cognitive function, but a rapid decline of glucose levels may impair cognitive function or may induce feelings of lack of energy. Low doses of caffeine may also enhance cognitive function, although most studies on caffeine and cognition, as with studies on glucose and cognition, have not been carried out in elderly individuals. The effects of nutritional supplements are modest but do not seem to be very different from those of medicinal or investigational cognition-enhancing or anti-dementia drugs.