PATIENTS WITH ALZHEIMER’S DISEASE ABLE TO MAKE COMPETENT TREATMENT DECISIONS

Patients with very mild Alzheimer’s disease are more likely to make competent decisions regarding treatment of their disease, suggested a study in the May 10 Neurology. Patients with mild to moderate Alzheimer’s disease had notable impairments in their ability to make treatment decisions, especially patients with moderate Alzheimer’s disease and patients who lacked awareness of symptoms, prognosis, or diagnosis.

Jason Karlawish, MD, of the University of Pennsylvania in Philadelphia, and colleagues interviewed 48 patients with very mild to moderate Alzheimer’s disease and 102 caregivers of patients with mild to severe Alzheimer’s disease. Interviews consisted of a modified version of the MacArthur Competency Assessment Tool for Treatment; this instrument measures the patients’ abilities to understand, appreciate, reason, and make a choice. Three expert psychiatrists judged competency upon reviewing the patient interviews.

Nineteen of the 48 patients were found to be competent decision-makers. According to the researchers, patients who affirmed that they had memory and thinking problems scored better on reasoning and appreciating the benefits of treatment than patients who did not affirm these problems. The same was true for patients who affirmed that they were aware that these problems would get worse. In addition, patients who were aware of their diagnosis scored better on measures of reasoning, understanding, and appreciating the benefits of treatment than those who were not aware of their diagnosis. Awareness of prognosis was associated with being judged competent, independent of overall cognitive function, the investigators noted.

Only 15% of patients fully appreciated the benefits of treatment, while 52% could not appreciate the benefits at all. In contrast, 48% understood the risks associated with treatment. According to Dr. Karlawish and his colleagues, 40% of patients scored as well as the majority of caregivers on the ability to reason—or, in other words, the ability to integrate information about the risks and benefits of treatment into their daily life. “Performance on the ability to reason may be a good way to distinguish competent from noncompetent patients,” they said.

When scores on the Mini-Mental State Examination (MMSE) were assessed, researchers found that patients who scored less than 19, indicating moderate Alzheimer’s disease, were less likely to be competent. Patients with a score of 23 or higher, indicating very mild Alzheimer’s disease, were very likely to be competent. However, those with a score of 20 to 23, indicating mild to early Alzheimer’s disease, are in the gray zone, said Dr. Karlawish. The researchers suggested that the MMSE could serve as a guide for a clinician to formulate the likelihood of a patient not being competent.

“These results are yet another reason why people should consult a doctor if they notice any warning signs of Alzheimer’s [disease] in themselves or a loved one,” concluded Dr. Karlawish. “An early diagnosis can help ensure that patients can participate in decisions about their care.”

Karlawish JHT, Casarett DJ, James BD, et al. The ability of persons with Alzheimer’s disease (AD) to make a decision about taking an AD treatment. Neurology. 2005;64:1514-1519.

GPi AND STN DEEP BRAIN STIMULATION ARE COMPARABLE FOR THE MANAGEMENT OF PARKINSON’S DISEASE

Stimulation of either the globus pallidus interna (GPi) or the subthalamic nucleus (STN) improves features of advanced Parkinson’s disease, according to Valerie C. Anderson, PhD, and colleagues. Furthermore, there is no clear superiority of STN—which is thought to be the preferred target for deep brain stimulation (DBS) in patients with advanced Parkinson’s disease—over GPi stimulation, noted the researchers in a report published in the April Archives of Neurology. Therefore, they said that “it is premature to exclude GPi as an appropriate target for DBS.”

Twenty-three patients ages 20 to 80 with idiopathic Parkinson’s disease, levodopa-induced dyskinesia, and response fluctuations were randomized to receive stimulation of either the GPi or the STN. Twenty patients completed the 12-month follow-up. All patients were evaluated using the Unified Parkinson’s Disease Rating Scale (UPDRS) while on and off medication and after three, six, and 12 months of DBS.

After 12 months of DBS, off-medication UPDRS motor scores improved by 39% in patients who received GPi stimulation and by 48% in patients who received STN stimulation. Twelve months of DBS at either site improved rigidity, bradykinesia, tremor, and axial symptoms such as speech, gait, posture, and postural stability, although bradykinesia and axial symptoms both improved more with STN stimulation than with GPi stimulation. In addition, off-medication activities of daily living improved by 23% in all patients. The researchers noted that no improvement in on-medication function was observed in either group.

Dr. Anderson and her colleagues found that levodopa dose was reduced by 38% in the STN stimulation group compared with only 3% in the GPi stimulation group. Nevertheless, they said, dyskinesia was improved in both groups, although the mechanism of dyskinesia reduction may be different at the two sites.

The researchers concluded that their study results yielded insufficient evidence to support the superiority of STN over GPi stimulation in the management of motor symptoms of advanced Parkinson’s disease.

In an accompanying editorial, Michael S. Okun, MD, and Kelly D. Foote, MD, stated that “the unanswered questions regarding target selection will require several more head-to-head rematches between GPi and STN…. Whatever the outcome of these rematches, we should be open to changes in our current practices and recognize the possibility that we should match individual patient needs with the strengths and weaknesses of individual targets.”

Anderson VC, Burchiel KJ, Hogarth P, et al. Pallidal vs subthalamic nucleus deep brain stimulation in Parkinson’s disease. Arch Neurol. 2005;62:554-560.
Okun MS, Foote KD. Subthalamic nucleus vs globus pallidus interna deep brain stimulation, the rematch. Arch Neurol. 2005;62:533-536.

DIETARY FOLATE INTAKE AND COGNITIVE DECLINE IN THE ELDERLY

High intake of folate may be associated with cognitive decline in older persons, suggested a study in the April Archives of Neurology. Conversely, those with higher intake of vitamin B12 showed slower decline in cognitive function, said Martha Clare Morris, ScD, and colleagues.

A total of 3,718 people 65 and older participated in the study. Change in cognitive function was measured at baseline and at three- and six-year follow-up using the following cognitive tests: the East Boston Tests of immediate and delayed recall, the Mini-Mental State Examination, and the Symbol Digit Modalities Test of perceptual speed and attention. Diet was assessed using a modified Harvard Food Frequency Questionnaire, which inquired about usual intake of 139 food items and vitamin supplements during the past year.

Thirty-three percent of the cohort reported consuming multivitamins. Those with high intake of total folate were more likely to experience cognitive decline than were individuals with low intake, more years of education, higher baseline cognitive scores, and greater consumption of vitamin E and vitamin C. They also had a faster rate of cognitive decline. The rate of cognitive decline among individuals in the top fifth of total folate intake (median, 742 μg/day) was more than twice that of those in the lowest fifth of total folate intake (median, 186 μg/day), said researchers. High folate intake from food and folate vitamin supplementation of more than 400 μg/day were also associated with a faster rate of cognitive decline. High total vitamin B12 intake, on the other hand, was associated with slower cognitive decline, but only among the oldest participants.

According to Ms. Morris and her colleagues, the observed association between high folate intake and cognitive decline was opposite what they had hypothesized. “We expected a slower rate of decline because low folate status is a cause of elevated homocysteine levels, which some but not all studies have found to be associated with increased risk of Alzheimer’s disease,” they explained.

The researchers are unsure of the mechanism by which high folate intake may increase cognitive decline. “One possibility,” they said, “is that high intake may be masking unrecognized vitamin B₁₂ deficiency…. [F]olic acid may exacerbate the neurologic syndrome associated with vitamin B₁₂ deficiency.”

According to the researchers, one limitation of the study is its reliance on food frequency questionnaires to measure intake. The absence of corresponding measure of tissue concentrations of these micronutrients prevented the researchers from examining whether vitamin deficiency could account for the results.

Ms. Morris’ research group concluded, “The possibility that high intake of folic acid through multivitamins and fortified food may have deleterious effects on the health of the older population warrants further study.”

Morris MC, Evans DA, Bienias JL, et al. Dietary folate and vitamin B12 intake and cognitive decline among community-dwelling older persons. Arch Neurol. 2005;62:641-645.

NO ASSOCIATION FOUND BETWEEN BLOOD MERCURY LEVELS AND NEUROBEHAVIORAL FUNCTION

Results from a recent study do not provide evidence that blood mercury levels are associated with worse neurobehavioral performance in older adults. Megan Weil, MHS, and colleagues sought to determine whether mercury found in fish—the consumption of which is widely recommended for older adults—could have negative neurobehavioral effects in older adults at consumption levels below those currently recommended by the Environmental Protection Agency and the National Research Council. Details of their study were published in the April 20 JAMA.

The researchers assessed data from 474 participants of the Baltimore Memory Study. Participants were between the ages of 50 and 70; 325 were women, 185 were black, and 263 were white. Researchers measured total mercury in whole blood samples and used multiple linear regression to examine its associations with neurobehavioral test scores. Trained technicians administered 20 neurobehavioral tests in the following seven domains: nonverbal reasoning and intelligence, language, verbal memory, visual memory, visuoconstruction and visuoperception, motor and manual dexterity, and executive function. Data on fish consumption were obtained through self-report using the Block 98.2 Food Frequency Questionnaire.

The researchers found that the median blood mercury level was 2.1 μg/L (range, 0 to 16 μg/L). Increasing blood mercury levels were associated with worse performance on Rey Complex Figure–Delayed Recall, a test of visual memory, and better performance on finger tapping, a test for manual dexterity.

Ms. Weil and her colleagues commented, “In evaluating whether toxicants have adverse effects on central nervous system function, it is important to consider whether exposure was recent or cumulative, whether effects are acute or chronic, and whether the biomarker is adequate to assess differing dose patterns…. If patterns of fish consumption vary dramatically over a lifetime, then a single blood mercury level may not be adequate to assess longer latency effects or effects related to cumulative dose, particularly if individuals were exposed in utero.”

The researchers concluded, “Since the blood mercury levels in our study did not appear to be associated with adverse neurobehavioral effects, our results suggest that these levels of exposure may not present a concern for older adults.” However, further assessment is necessary to confirm these results “since a single blood mercury level may not be an optimal estimate of cumulative dose.”

Weil M, Bressler J, Parsons P, et al. Blood mercury levels and neurobehavioral function. JAMA. 2005;293:1875-1882.

NEW OLIGOCLONAL BAND TEST FOR THE DIAGNOSIS OF MULTIPLE SCLEROSIS

A new oligoclonal immunoglobulin (IgG) band test accurately differentiates early multiple sclerosis (MS) from other neurologic diseases, according to a report in the April issue of Archives of Neurology. Researchers from the Hospital Ramón y Cajal and the University of Alcalá, both in Madrid, said that this new method shows high sensitivity and definition and is easier to interpret than current methods.

Luisa M. Villar, PhD, and colleagues studied 385 patients with various neurologic disorders. Isoelectric focusing and IgG immunodetection by an alkaline phosphatase–labeled anti-IgG antibody were used to measure the presence of oligoclonal IgG bands in serum and cerebrospinal fluid samples.

Intrathecal IgG synthesis was found in 96.2% of patients with MS, 35.3% of patients with central nervous system infections, and one patient with motor neuron disease. Two patterns reflected intrathecal IgG synthesis—one showed oligoclonal IgG bands restricted to cerebrospinal fluid and was predominantly found in patients with MS, and the other showed oligoclonal IgG bands in serum and additional bands in cerebrospinal fluid and was found in patients with central nervous system infections. No patients with other inflammatory neurologic diseases showed intrathecal IgG synthesis.

Patients who lacked intrathecal IgG synthesis showed an increased percentage of mirror patterns in central nervous system infections, neoplastic meningitis, inflammatory diseases of the peripheral nervous system, and inflammatory diseases of the central nervous system other than MS. The researchers pointed out that this pattern is absent from patients with MS.

Among patients with MS, no significant differences were found in the percentage of positive samples between patients who underwent lumbar puncture after their first attack and those in whom lumbar puncture was performed after the second attack, when the diagnosis of clinically definite MS was made. Therefore, the researchers conjectured that intrathecal IgG synthesis could be helpful in the early diagnosis of MS. “An early diagnosis of MS helps to initiate treatment as soon as possible, improving the quality of life of the patients,” commented Dr. Villar.

According to the researchers, the sensitivity of the oligoclonal IgG band test was 96.2% and the specificity was 92.5%. “Although the usefulness of this technique in the diagnosis of MS should be confirmed with studies performed in multiple laboratories, these results reinforce the value of oligoclonal band studies in the early differential diagnosis of MS,” Dr. Villar and her colleagues concluded.

Villar LM, Masjuan J, Sadaba MC, et al. Early differential diagnosis of multiple sclerosis using a new oligoclonal band test. Arch Neurol. 2005;62:574-577.

EXPOSURE TO PESTICIDES IS ASSOCIATED WITH NEUROLOGIC SYMPTOMS

Cumulative exposure to moderate levels of pesticides is associated with increased neurologic symptoms in licensed private pesticide applicators, according to a study in the April 15 online edition of Environmental Health Perspectives. Using data from a cohort of 18,782 North Carolina and Iowa farmers, Freya Kamel, PhD, MPH, of the National Institute of Environmental Health Sciences, and colleagues linked use of insecticide to reports of headaches, fatigue, insomnia, dizziness, nausea, hand tremors, numbness, and other neurologic symptoms.

Of approximately 52,400 individuals applying for new or renewed pesticide licenses, 18,782 completed two questionnaires collecting information on frequency and duration of use of 50 specific pesticides as well as information on demographic characteristics, lifestyle, high pesticide exposure events, medical visits for pesticide-related illness, and pesticide poisoning. To reduce heterogeneity, the analysis was restricted to white men ages 18 to 75, who comprised 92% of the group that was otherwise eligible.

Individuals in the highest quartile of lifetime days of pesticide use were 1.2 times as likely to experience 10 or more symptoms and averaged 0.6 more symptoms in the year preceding enrollment, compared with those in the lowest quartile. Increased symptom count was also associated with a history of pesticide poisoning or events involving high personal pesticide exposure.

Additionally, associations with cumulative pesticide use persisted even after exclusion of individuals with a history of pesticide poisoning or high exposure events, as well as individuals who reported recent pesticide use (within the year prior to enrollment in the study).

Finally, though symptom count was related to all classes of pesticides, organophosphate, carbamate, and organochlorine insecticides were independently associated with increased risk, the investigators noted.

Dr. Kamel and her colleagues concluded that although high levels of exposure to pesticides are known to be neurotoxic, more attention to the risks associated with moderate exposure to pesticides might be required.

Kamel F, Engel LS, Gladen BC, et al. Neurologic symptoms in licensed private pesticide applicators in the agricultural health study. Environ Health Perspect. 2005. E-pub ahead of print.

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