A diet high in fruits, vegetables, and fish appears to significantly reduce the risk of dementia or Alz-heimer’s disease, especially among study participants without the apolipoprotein E (APOE) e4 variant, reported researchers in the November 13 Neurology. The study included 8,085 participants, all of whom were 65 and older and free of dementia at baseline; however, during four years of follow-up, 281 cases of dementia were observed, including 183 cases of Alzheimer’s disease. Participants who consumed fruits and vegetables daily were less likely to develop dementia (hazard ratio [HR], 0.72). Weekly consumption of fish was associated with a reduced risk of Alzheimer’s disease (HR, 0.65) and dementia, but only among APOE e4 noncarriers (HR, 0.60). In addition, an increased risk of dementia was also observed in APOE e4–negative participants who regularly consumed omega-6 rich oils without a balance of omega-3 rich oils (HR, 2.12). According to lead study author Pascale Barberger-Gateau, PhD, of INSERM, the French National Institute for Health and Medical Research in Bordeaux, further investigation is warranted. “While we’ve identified dietary patterns associated with lowering a person’s risk of dementia or Alz-heimer’s disease, more research is needed to better understand the mechanisms of these nutrients involved in these apparently protective foods.”

The treatment plan and dosing paradigm of lamotrigine in pregnant women can improve with therapeutic drug monitoring, according to the results of a study published in the November 28 online Neurology. Three hundred five blood samples were prospectively collected from 53 pregnant women every one to three months; seizure and medication diaries were reviewed, and examinations were conducted. The investigators reported that total and free lamotri-gine clearance significantly increased above baseline during all trimesters, with peak clearances occurring during the third trimesters (94% and 89%, respectively); free clearance was greater in white women than in black women, they added. “Increased seizure frequency in the second trimester was associated with a lower ratio to target concentration, and ratio to target concentration < 0.65 was a significant predictor of seizure worsening,” stated the authors. The researchers also found that empiric postpartum tapering decreased the likelihood of maternal lamotrigine toxicity and that the newborn outcomes were similar to those among the general population.

A review of high-resolution structural brain MRIs from 2,000 subjects from the population-based Rotterdam Study revealed abnormalities, including subclinical vascular pathologic changes, according to a study in the November 1 New England Journal of Medicine. Researchers found that asymptomatic brain infarcts were the most common abnormality, which was found in 7.2% of the participants; cerebral aneurysms and benign primary tumors (mainly meningiomas) were also found in 1.8% and 1.6% of the group, respectively. The age of the participants ranged from 45.7 to 96.7 years, with a mean age of 63.3. “The prevalence of asymptomatic brain infarcts and meningiomas increased with age, as did the volume of white-matter lesions, whereas aneurysms showed no age-related increase in prevalence,” said the authors. “Information on the natural course of these lesions is needed to inform clinical management.”

Mice fed a diet high in omega-3 polyunsaturated fatty acids (PUFAs) showed significantly less neuronal death and a reduction in dopamine levels following a toxic challenge than mice fed a control diet. This finding suggests a neuroprotective effect of omega-3 PUFAs against Parkinsonism. As reported in the November 21 online FASEB Journal, mice were fed one of the two diets from 2 to 12 months of age and then treated with the neurotoxin 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP). Although control mice showed a 31% decrease in tyrosine hydroxylase-labeled nigral cells, the decrease was prevented completely in mice with high omega-3 PUFA dietary consumption. In addition, mice receiving the dietary treatment also had decreases in Nurr1 mRNA and dopamine transporter mRNA levels, said the investigators. The experimental diet also protected against a decrease in striatal dopamine (vs a 50% decrease in control mice) and its metabolite dihydroxyphenylacetic acid. The research team’s findings could help prevent the disease and potentially slow down disease progression.

White matter changes following traumatic brain injury (TBI) occur on a spectrum, and even mild TBI can cause significant changes, per a study in the October Brain. Patients with moderate to severe TBI (n = 17) showed decreased white matter integrity via diffusion tensor imaging in 13 brain regions of interest, with both axonal and myelin damage, as compared with 18 healthy controls. The mild TBI group (n = 20) also showed decreased white matter integrity, but only in the corticospinal tract, sagittal stratum, and superior longitudinal fasciculus; however, the damage appeared to be solely axonal in nature. The investigators also reported that the number of regions with damage was related to cognitive function “such that greater white matter pathology predicted greater cognitive deficits.”

A higher education level has a contradictory effect on the timeline of decline in memory among persons with dementia, according to a study in the October 23 Neurology. Investigators made their findings after studying the influence of education on rates of memory decline in 117 patients with incident dementia from the Bronx Aging Study. Each year of formal education delayed the time to accelerated decline in Buschke Selective Reminding Test scores by 0.21 years, but the rate of memory decline, once it began, was increased by 0.10 points per year for each additional year of education. The researchers estimated that a person with 16 years of formal education would experience a rate of memory decline that is 50% faster than that of a person with four years of education. “This rapid decline may be explained by how people with more education have a greater cognitive reserve,” posited the authors; they also suggested that symptoms may emerge only after the cognitive reserve can no longer compensate for the damage that has already occurred.

A biological analysis of 18 signaling proteins found in blood plasma was able to distinguish between samples from patients with Alzheimer’s disease and nondemented control subjects, as reported in the November Nature Medicine. “To find an Alzheimer’s-specific signature, we analyzed [the training set with] predictive analysis of microarrays,” which identified 18 predictors out of 120 known signaling proteins, said the researchers. In a testing set, the signature classified Alzheimer’s disease samples with 90% positive agreement and non-Alzheimer’s disease samples with 88% negative agreement; 91% agreement was also achieved when applied to plasma samples from patients with mild cognitive impairment who developed Alzheimer’s disease two to five years later, while all samples from patients who later developed other dementias were correctly classified as “non-Alzheimer’s,” reported the researchers.

Researchers reported the first neural study of the effect of sleep in regulation of the human brain’s emotional response to negative stimuli in the October 23 Current Biology. fMRI scans were conducted as 26 healthy participants ages 18 to 30 were shown 100 images, the content of which ranged from neutral to very negative. Half of the participants had stayed awake for 35 straight hours, while the others slept a full night in their own beds. In control participants, the amygdala engaged with the medial-prefrontal cortex, which exerts “an inhibitory, top-down control of amygdala function, resulting in contextually appropriate emotional responses,” stated the researchers. However, in the sleep-deprived group, the brains mimicked pathologic psychiatric patterns with the release of noradrenalin by the locus coeruleus, leading to a hyperactive amygdala response to the negative stimuli.

Results of a study published in the November 27 Neurology support the hypothesis that metabolic stress plays a significant role in the poststroke period. Mini-Mental State Examination and modified Rankin Scale scores of 3,680 participants older than 35 who had a mild to moderate stroke “gradually improved” during the two-year follow-up period. However, independent predictors of less successful cognitive recovery included increased age, nonwhite race, recurrent stroke, left hemisphere cortical lesions, low HDL cholesterol, increased homocysteine, and diabetes mellitus; similar factors were identified for recovery of disability, although there were qualitative and quantitative differences, said the researchers. They also noted a threshold effect of homocysteine on cognitive recovery that began in the participants’ late 50s. The investigators concluded that more research is needed to determine why those factors contribute to slower stroke recovery.

NR