DIET AND DEMENTIA—DOES FAT MATTER?

Diet, at least intake of fats, may not have the etiologic relationship to dementia promulgated by various studies, according to researchers from the Departments of Epidemiology and Biostatistics at Erasmus Medical Center, Rotterdam, the Netherlands. The investigators examined whether high intake of total fat, saturated fatty acids, trans fatty acids, and cholesterol, and low intake of monounsaturated fatty acids, polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, and n-3 polyunsaturated fatty acids were associated with an increased risk of dementia and its subtypes. Their cohort of 5,395 participants was derived from the Rotterdam Study, a population-based, prospective, cohort study among the elderly. Mean age of participants in the dementia study at baseline was 68, and 59% were women. All participants had normal cognition, lived independently, and had reliable dietary assessments.

Data for dementia were drawn from the Mini-Mental State Examination, the Geriatric Mental State schedule, the Cambridge Examination of Mental Disorders in the Elderly, neurologic/neuropsychologic examination, and brain magnetic resonance imaging scan (when available). The cohort was monitored continuously for incident dementia. Information on diet was drawn from a baseline checklist indicating all food and drink consumed more than twice per month over the last year, an interview with a trained dietitian, and an extensive, validated food-frequency questionnaire.

Over a six-year follow-up, the researchers calculated the relationship between incidence of dementia and energy-adjusted intake of fat in a Cox’s proportional hazard model. Dementia was found in 197 participants (146 Alzheimer’s dementia, 29 vascular dementia, 22 other dementia). High intake of total fat, saturated fatty acids, trans fatty acids, and cholesterol, and low intake of monounsaturated fatty acids, polyunsaturated fatty acids, n-6 polyunsaturated fatty acids, and n-3 polyunsaturated fatty acids were not significantly associated with an increased risk of dementia or its subtypes. However, the investigators were quick to allow that it would be premature to conclude that cholesterol or cholesterol-affecting fats are not associated with dementia based on their observational study. They called for larger, prospective studies on the subject, with longer follow-up periods, in order to confirm their findings.

Suggested Reading
Engelhart MJ, Geerlings MI, Ruitenberg A, et al. Diet and risk of dementia: does fat matter? The Rotterdam Study. Neurology. 2002;59:1915-1921.

INCREASED BLOOD-BRAIN BARRIER PERMEABILITY FOUND IN PATIENTS WITH TYPE 2 DIABETES

Researchers have detected increased blood-brain barrier permeability in patients with type 2 diabetes as demonstrated by magnetic resonance imaging. This finding may account for some of the cerebral effects of type 2 diabetes, as well as for those of other conditions that affect the microvasculature on the brain. “In this small and comparatively preliminary study, we have demonstrated features consistent with increased blood-brain barrier permeability in diabetic patients compared with controls, and in those with more white matter hyperintensities than in those with fewer,” reported John M. Starr, of the University of Edinburgh, Western General Hospital, United Kingdom, and colleagues. “This simple technique is worthy of further development for use in studies of the effects of ‘vascular’ disease on the brain and of mechanisms of dementia.”

As detailed in the January issue of the Journal of Neurology, Neurosurgery and Psychiatry, Dr. Starr’s team evaluated 10 well-controlled male patients with type 2 diabetes, ages 65 to 70. Ten controls underwent cranial magnetic resonance imaging with fluid attenuated inversion recovery, T1-weighted volumetric imaging before, and T1-weighted volumetric imaging at five, 15, 30, 45, 60, and 90 minutes after intravenous gadolinium diethylenetriamine pentaacetic acid (Gd-DTPA). The investigators found that brain signal intensity increased more in the diabetic group than in controls during the first 15 minutes after Gd-DTPA, particularly in the basal ganglia. Signal intensity in controls peaked at five minutes and in diabetics at 15 minutes. Furthermore, individuals with more white matter hyperintensities had a greater signal increase after Gd-DTPA, regardless of whether they were diabetic.

“The findings from this study require replication in other subjects with diabetes and with white matter hyperintensities and various degrees of cognitive impairment,” the researchers concluded. “As the significant changes over time were seen comparatively early in diabetes, more frequent measurement of signal intensity after Gd-DTPA injection over the first 30 minutes may increase power to detect differences in blood-brain barrier permeability.... Should future studies confirm blood-brain barrier permeability as a correlate of brain pathology, the ability to quantify blood-brain barrier permeability in vivo will facilitate evaluation of targeted interventions.”

Suggested Reading
Starr JM, Wardlaw J, Ferguson K, et al. Increased blood-brain barrier permeability in type II diabetes demonstrated by gadolinium magnetic resonance imaging. J Neurol Neurosurg Psychiatry. 2003;74:70-76.

NEUROLOGIC ASPECTS OF BIOLOGICAL AND CHEMICAL TERRORISM

Several chemical and biological weapons affect the nervous system, and in the event of an emergency, awareness among neurologists is important for the diagnosis and treatment of victims. In the January Archives of Neurology, researchers from the University of Iowa College of Medicine, Iowa City, reviewed four agents that have a history of military or terrorist use—cyanide poisons, organophosphate poisons, botulinum toxin, and anthrax. The authors explained the weapon applications, clinical manifestations, and treatments of these agents.

Cyanide gases have the potential to cause sudden mass casualties. However, the types of symptoms and severity of illness depend on the level of exposure to the gases—large exposures typically result in death, while lesser exposures produce nonspecific symptoms. In cases of substantial exposure, loss of consciousness occurs within one minute, followed shortly by respiratory depression and cardiac arrest. Symptoms for lesser exposure include headache, nausea, seizures, and abnormal breathing, and can progress to coma within a few hours. In addition to perfunctory decontamination, treatment for severely infected patients includes life support, supplemental oxygen, and correction of metabolic acidosis.

Potent forms of organophosphates can be used as chemical weapons in the form of “nerve agents.” Organophosphates are rapidly absorbed into the lungs, and the time from exposure until clinical symptoms is brief. The chief symptoms of organophosphate poisoning are “excessive salivation and lacrimation as well as involuntary urination and defecation,” and with large doses, patients may present with seizures or coma. Severely affected patients require respiratory support, and atropine reverses bronchial constriction. Less severely affected patients also benefit from atropine.

The clinical features of botulinum toxin, regardless of whether it is ingested or inhaled, are the same. Symptoms may occur as soon as two hours or as late as eight days following exposure. Botulism affects the cranial nerves, causing “ptosis, poorly reactive dilated pupils, disconjugate gaze, facial diplegia, aspiration, and dysarthria.” The only specific treatment for botulism is passive immunization with antitoxin; the antitoxin may stabilize the effects caused by the existing paralysis but cannot reverse them.

While all three forms of anthrax can be complicated by meningitis, the risk of hemorrhagic meningitis in cases of inhalational anthrax is approximately 50%. Symptoms of inhalational anthrax occur less than a week after spores germinate. Initial symptoms include fever, chills, myalgia, cough, and sore throat. In the later stage, the bacteria produce toxins, causing tissue hemorrhage, edema, and necrosis, and patients subsequently develop sepsis, hypoxemia, cyanosis, and shock. Anthrax meningitis should be treated with multiple drugs, including ciprofloxacin and at least one other agent.

Suggested Reading
Martin CO, Adams HP Jr. Neurological aspects of biological and chemical terrorism: a review for neurologists. Arch Neurol. 2003;60:21-25.

APATHY IN PARKINSON’S DISEASE—SYMPTOM OR PSYCHOLOGICAL REACTION TO DISABILITY?

Apathy in Parkinson’s disease is a consequence of disease-related physiologic changes, rather than a psychological reaction to the disability, stated researchers in the December 2002 Journal of Neurology, Neurosurgery and Psychiatry. They sought to determine the relation between apathy and cognitive impairments. The researchers also assessed the association between apathy and aspects of personality, and whether apathy can be considered a symptom of Parkinson’s disease or merely a reaction to the disability.

Researchers examined 45 patients with Parkinson’s disease and 17 patients with osteoarthritis, choosing patients with osteoarthritis as the control group because of “the age range of the patient population and the facts that the condition is chronic, progressive, and causes significant levels of disablement.” A battery of tests assessed apathy, global cognitive function, executive function, mood, hedonic tone, and personality. The investigators conducted two sets of comparisons. The first was between the patients with Parkinson’s disease and those with osteoarthritis; the second was within the Parkinson’s disease group, between those identified as having high and low levels of apathy.

Seventeen patients with Parkinson’s disease were classified as having “high apathy,” while 28 patients were categorized as having “low apathy.” No one from the osteoarthritis group was identified as apathetic. Researchers reported little difference between the Parkinson’s disease group and the osteoarthritis group in terms of global cognitive impairment, anxiety, personality, and hedonic tone. They did find that the Parkinson’s disease group was more prone to depression, however, and that those with high apathy scored significantly more poorly on cognitive measures than those patients with low apathy. The researchers believe that these results “support the conclusion that apathy is a true feature of the Parkinson’s disease progress and not a psychological response to physical impairment and associated disability.”

HIGH LEVELS OF PLASMA PROTEINS INCREASE RISK OF STROKE

High inflammation-sensitive plasma protein levels are associated with an increased risk of stroke among men with high blood pressure, according to a study in the December issue of Stroke. The researchers chose five inflammation-sensitive plasma proteins—fibrinogen, a1-antitrypsin, haptoglobin, ceruloplasmin, and orosomucoid—that have been associated with increased incidences of myocardial infarction and stroke. Researchers investigated the relationships between inflammation-sensitive plasma proteins and blood pressure, as well as the long-term effects of inflammation-sensitive plasma proteins and blood pressure on incidence of stroke.

The investigators assessed the blood pressure and inflammation-sensitive plasma proteins of 6,071 healthy men between the ages of 28 and 61 from data gathered between 1974 and 1983. The patients were classified as smokers or nonsmokers. Each patient’s blood pressure was measured twice, and researchers used the average of the two measurements for the analysis. Blood samples were taken after an overnight fast, specifically looking at plasma cholesterol and triglyceride concentrations. Because the risk of cardiovascular diseases increases between the third and fourth quartiles of inflammation-sensitive plasma protein, researchers categorized the sample according to the number of proteins in the top quartile. Each case was followed up from baseline until death or December 31, 1997.

The investigators found that blood pressure increased with the number of inflammation-sensitive plasma proteins in the top quartile, and, with the exception of haptoglobin in smokers, all inflammation-sensitive plasma proteins were significantly correlated with systolic blood pressure. A total of 919 men died during follow-up, 378 due to cardiovascular disease. The incidence of stroke was highest among men whose systolic blood pressure was greater than 140 mm Hg and who had two to five inflammation-sensitive plasma proteins in the top quartile. Researchers concluded that “while hypertension is strongly associated with stroke, there are great differences between hypertensive men with similar blood pressure levels,” but association between high inflammation-sensitive plasma protein levels and stroke remains unclear.

NR

Suggested Reading
Engström G, Lind P, Hedblad B, et al. Long-term effects of inflammation-sensitive plasma proteins and systolic blood pressure on incidence of stroke. Stroke. 2002;33:2744-2749.

Return to table of contents