CONVENTIONAL NSAIDS HAVE SIMILAR PROTECTIVE EFFECT FOR ALZHEIMER'S DISEASE

Although NSAIDs reduce the risk for Alzheimer’s disease, no apparent advantage in risk reduction was observed regarding Aβ₄₂-lowering NSAIDs, reported Chris A. Szekely, PhD, and colleagues in the June 10 Neurology.

The researchers examined six prospective studies of patients with Alzheimer’s disease who were taking OTC and prescription NSAIDs prior to dementia diagnosis. The frequency of NSAID use at any time in the follow-up interval was 29.6%. Aspirin was used by 40.7% of patients, and 25.3% had used acetaminophen. NSAID users tended to be women, highly educated, and younger at baseline. Ibuprofen was the most commonly used selective Aβ₄₂-lowering agent (SALA), accounting for 52.9% of NSAID use. Naproxen was the most commonly used non-SALA (20.4% of NSAID use). No gender differences were found regarding SALA use, compared with non-SALA use.

Of the 13,499 study participants, 820 developed Alzheimer’s disease, according to Dr. Szekely of the Johns Hopkins Bloomberg School of Public Health in Baltimore, and coauthors. Risk of Alzheimer’s disease was reduced by NSAID use (hazard ratio [HR], 0.75; adjusted hazard ratio [aHR], 0.77). Those who used aspirin with no other NSAID also had a reduced risk of Alzheimer’s disease (aHR, 0.78). There was no significant association between acetaminophen use and Alzheimer’s disease (aHR, 0.93).

SALA and non-SALA NSAID groups showed a similar reduction in risk for Alzheimer’s disease (aHR, 0.87 and 0.75, respectively). Among the 573 people who had used both NSAID types, there was no significant difference in the independent use of SALAs (aHR, 0.82), non-SALAs (aHR, 0.60), and the combination of the two (aHR, 0.87). Similar associations with Alzheimer’s disease were observed in the use of ibuprofen (aHR, 0.88) and naproxen (aHR, 0.55).

Study characteristics were homogenous enough to allow pooling of individual-level data; “the different criteria for ‘use’ resulted in varying baseline rates of NSAID use, but they did not appear to affect the relationship between exposure and outcome, which was itself measured with consistent results,” noted the researchers. One study produced somewhat different results, due to being one of the older studies, drawing participants from slightly lower socioeconomic regions, and consisting of more ibuprofen exposure. “A better understanding of these effects will be important, even if the current generation of drugs has limitations,” commented the authors.

Suggested Reading
Szekely CA, Green RC, Breitner JCS, et al. No advantage of Aβ₄₂-lowering NSAIDs for prevention of Alzheimer dementia in six pooled cohort studies. Neurology. 2008;70(24):2291-2298.

OPTIC NEURITIS MRI ABNORMALITIES PREDICT MS ONSET

The presence of lesions on MRI scans at the time of an optic neuritis attack is strongly associated with the development of multiple sclerosis (MS), according to a study in the June Archives of Neurology.

Researchers from the Optic Neuritis Study Group acquired information from subjects with acute unilateral optic neuritis from the Optic Neuritis Treatment Trial (ONTT; n = 389), in which patients were randomized to corticosteroid use or placebo and examined at five, 10, and 15 years.

The overall probability of developing MS by the 15-year exam was 50%. In patients with no lesions, the probability decreased to 25%; when a patient had one or more lesions, the probability increased to 72%. Risk did not substantially increase with the addition of more than one lesion. Among the three ONTT groups, there was no difference in risk of developing MS; 45% of patients developed MS in the IV corticosteroid group, 51% in the oral corticosteroid group, and 53% in the placebo group.

MS onset was highest in the first five years—occurring among 16% of patients with no lesions and in 42% of patients with one or more lesions. The probability of acquiring the disease between the 10- and 15-year examinations was 32% in subjects with one or more lesions and 2% in those with none.

For the Expanded Disability Status Scale, 67% of participants had a score of less than 3 and 13% had a score of at least 6. Degree of disability was not related to number of lesions at baseline, as 39% of patients with no baseline lesions and 31% of patients with one or more lesions had moderate or severe disability. Of these patients, 67 (59%) reported current use of disease-modifying therapy, 26 (23%) reported use in the past but no current use, and 20 (18%) reported no current or past use.

“The very low risk of MS when atypical features of optic neuritis are present highlights the importance of an ophthalmologic examination to identify these features, particularly for patients with normal brain MRI findings,” the researchers stated. They recommended balancing the risk of developing MS with potential adverse effects of disease-modifying agents for patients with an abnormal brain MRI.

Suggested Reading
Optic Neuritis Study Group. Multiple sclerosis risk after optic neuritis: final optic neuritis treatment trial follow-up. Arch Neurol. 2008;65(6):727-732.

DEEP BRAIN STIMULATION FOR PARKINSON'S DISEASE AFFECTS COGNITIVE DECLINE

Patients with Parkinson’s disease who underwent subthalamic nucleus deep brain stimulation (STN DBS) experienced mild frontostriatal cognitive declines—including verbal recall and oral information processing—even when good motor outcome was achieved, reported Michele K. York, PhD, of the Baylor College of Medicine in Houston, and coauthors.

The researchers assessed 23 patients with Parkinson’s disease who underwent STN DBS and 27 controls with Parkinson’s disease in a study in the July Journal of Neurology, Neurosurgery, and Psychiatry. At the six-month follow-up after surgery, DBS patients were taking 64% less dopaminergic medication, compared with controls who took 3% more dopaminergic medication. While “on” stimulator, 83% of DBS patients showed an improvement in their “off” medication motor scores, compared with 26% of post-DBS patients who showed improvement when “on” stimulator and medication. Dyskinesias, assessed per the Unified Parkinson’s Disease Rating Scale and disability ratings, improved significantly after DBS. Overall, patients who received DBS had improved motor scores during their “off” medication period, with a reduction from 50% of the day to 25% of the day regarding dyskinesias.

Adversely, 26% of DBS patients demonstrated verbal fluency decline, compared with 4% of controls with Parkinson’s disease; however, this was not significant after controlling for group differences in age of onset and presurgical dopaminergic dosage. DBS patients had a 20% decline in the number of words recalled after 30 minutes on the Rey Auditory Verbal Learning Test (RAVLT); 13% of patients who underwent DBS had a reliable decline for RAVLT long-term recall versus 0% of controls. The Stroop Word score and Symbol Digit Modalities Test showed decline trends for six months postsurgery among DBS subjects, suggesting that oral information processing performance was negatively affected. Verbal processing corresponded with frontostriatal dysfunction and was not due to disease progression alone; however “the verbal fluency decline may be the result of decreased dopaminergic stimulation of frontal areas due to medication changes,” Dr. York and colleagues suggested.

Other neurologic declines were observed in the DBS group, but these corresponded with control group dysfunction and, thus, disease progression. “Our findings underscore the need for surgical outcome studies to include disease control groups for comparison to distinguish the progression of the disease from the changes related to the intervention,” the authors noted. They recommended further investigation of the pathophysiology of cognitive and psychiatric changes after surgery.

Suggested Reading
York MK, Dulay M, Macias A, et al. Cognitive declines following bilateral subthalamic nucleus deep brain stimulation for the treatment of Parkinson’s disease. J Neurol Neurosurg Psychiatry. 2008;79(7):789-795.

DEMENTIA SYMPTOMS ARE DECREASED BY LIGHT AND MELATONIN

The combined use of bright light and melatonin has beneficial effects on dementia, according to a study in the June 11 JAMA.

Participants (87% had dementia) from 12 elder care facilities were randomized to either bright light (1,000 lux; n = 98) or dim light (300 lux; n = 91) daily by Rixt F. Riemersma–van der Lek, MD, of the Netherlands Institute for Neuroscience, Royal Netherlands Academy of Arts and Sciences in Amsterdam, and colleagues. Both groups of patients (mean age, 85.8; female, 90%) were then randomized to take melatonin (2.5 mg/day; n = 95) or placebo (n = 94) about one hour before bedtime. Follow-up assessments were made six weeks after treatment and then every six months for up to 3.5 years (mean follow-up time, 15 months).

Light alleviated cognitive deterioration by a mean of 0.9 on the Mini-Mental State Examination, or a relative 5%. Depressive symptoms were decreased by 1.5 points on the Cornell Scale for Depression in Dementia, or a relative 19%. Functional limitations were attenuated by 1.8 points per year on the nurse-informant activities of daily living scale (relative 53%).

Melatonin reduced sleep-onset latency by 8.2 minutes (19%) and increased sleep duration by 27 minutes and with light treatment an additional 10 minutes per year, observed Dr. Riemersma–van der Lek and coauthors. However, treatment negatively affected mood ratings on the Philadelphia Geriatric Center Affect Rating Scale (PGCARS), lowering the mean positive rating by 0.55 points (5%) and increasing the mean negative rating by 0.82 points (14%).

Combined treatment of light and melatonin decreased the mean PGCARS negative score by 1 point (17%). Mean agitated behavior score decreased by 3.9 points on the Cohen-Mansfield Agitation Inventory (9%). This treatment also increased sleep efficacy by 3.5% and improved nocturnal restlessness by one minute per hour each year (9%).

Suggested Reading
Riemersma–van der Lek RF, Swaab DF, Twisk J, et al. Effect of bright light and melatonin on cognitive and noncognitive function in elderly residents of group care facilities: a randomized controlled trial. JAMA. 2008;299(22):2642-2655.

Return to table of contents