CAN STATINS PROTECT AGAINST MS?

Investigators have determined that, because of their anti-inflammatory properties, cholesterol-lowering statins merit evaluation as possible treatment for multiple sclerosis. The researchers investigated the impact of statins on a variety of immune responses in multiple sclerosis, comparing the effects with those induced by interferon ß-1b. The study was published in the October 8 Neurology.

Researchers examined blood from 74 patients with either relapsing-remitting multiple sclerosis or secondary progressive multiple sclerosis and from 25 healthy donors. Thirty-nine patients were treated with interferon ß-1a, 19 with interferon ß-1b, and 16 patients received no treatment. Peripheral blood mononuclear cells were stimulated in vitro with simvastatin, lovastatin, mevastatin, interferon ß-1b, and interferon ß-1b plus statins. Investigators monitored the activity of T cells and B cells, the production and release of cytokines, the activity of matrix metalloproteinases (MMP), and the surface expression of activation markers, adhesion molecules, and chemokine receptors on T and B cells.

The three statins inhibited proliferation of T cells in a dose-dependent manner, with simvastatin being the most potent. However, the inhibitory effects of statins on B cells were low. All three statins reduced the expression of chemokine receptors in both T and B cells and reduced the expression of adhesion molecules on T cells. These effects were comparable to those seen with interferon ß-1b. Simvastatin helped to modify the T helper 1/T helper 2 balance, and it also inhibited the activity of MMP-9, although this effect was less pronounced than the inhibition shown with interferon ß-1b. Researchers believe that because “the treatment of patients with multiple sclerosis with interferon ß-1 did not significantly modify the action of statins compared to untreated patients or to healthy donors,” statins may be a useful add-on therapy.

Suggested Reading
Neuhaus O, Strasser-Fuchs S, Fazekas F, et al. Statins as immunomodulators: comparison with interferon-ß1b in MS. Neurology. 2002;59:990-997.

REVERSIBLE CONDITIONS OFTEN SEEN IN PATIENTS WITH MILD COGNITIVE IMPAIRMENTS

Researchers from the Copenhagen University Hospital have determined that potentially reversible conditions are often seen in patients with mild cognitive disturbances. The investigators defined a reversible condition as one known to be “potentially reversible or arrestable either on treatment or spontaneously” and “responsible for, or contributing to, the observed cognitive symptoms or dementia.” They investigated the prevalence and classification of reversible conditions in a memory clinic cohort.

Investigators evaluated 1,000 consecutive patients (mean age, 66) who were referred to the memory clinic at the Copenhagen University Hospital; the patients completed the diagnostic evaluation during a 54-month period, and all patients presented with cognitive symptoms. The patients also took a battery of neuropsychologic tests covering six cognitive domains: memory, concentration and attention, abstraction and problem solving, language, visual perception, and visuoconstruction. Each patient’s cognitive profile was classified into one of the following groups: dementia fulfilling DSM-IV criteria, isolated amnesia (not fulfilling dementia criteria), other cognitive deficits, no significant cognitive deficits, uncertain test data, and not classified. In addition, the primary etiology of the cognitive profile was established, as were concomitant conditions that could contribute to the cognitive symptoms.

Of the 1,000 patients, 43% met the criteria for dementia, 15% for isolated amnesia, and 2% for other cognitive deficits. No cognitive deficits were seen in 29% of the patients, and the remaining patients were not classified. Researchers determined that 19% of the patients had potentially reversible conditions. However, only 4% of patients diagnosed with dementia had a potentially reversible condition. Of the reversible diagnoses, the most common—found in 82% of all patients with reversible conditions—were depression, hydrocephalus, and alcohol dependence syndrome. Investigators felt that “although potentially reversible conditions may not be fully reversible on treatment, the identification and treatment of these conditions are essential elements of early diagnostic evaluation of dementia.” The results of this study were published in the October issue of the Journal of Neurology, Neurosurgery and Psychiatry.

Suggested Reading
Hejl A, Høgh P, Waldemar G. Potentially reversible conditions in 1000 consecutive memory clinic patients. J Neurol Neurosurg Psychiatry. 2002;73:390-394.

PREDICTING GROSS MOTOR FUNCTION IN CEREBRAL PALSY

Researchers have developed a way to anticipate the gross motor progress in children with cerebral palsy, according to an article in the September 18 JAMA. As an answer to parents concerned about the severity of their child’s impairment, the investigators described patterns of gross motor development by severity using longitudinal observations. They used these prognoses as the basis for educating families and providing clinicians with increased prognostic information.

The researchers identified all children from 19 rehabilitation programs in Ontario who had been diagnosed as having cerebral palsy. Of this sample, 657 of the children, whose ages ranged from 1 to 13 years, had fully useable data. At the first assessment, investigators reported the distribution of the child’s cerebral palsy (hemisyndrome, diplegia, triplegia, or quadriplegia) as it was stated in the child’s clinic chart. Each child’s motor function was ascertained using the Gross Motor Function Measure, a 100-point scale that measures gross motor function in lying and rolling, crawling and kneeling, sitting, standing, and walk-run-jump activities. To track individual gross motor development, children younger than 6 years were assessed every six months, while older children were assessed every nine to 12 months.

The investigators recorded an average of four observations per child over the course of the study. Based on these observations, they created five “distinct and significantly different motor growth curves,” which described patterns of gross motor development according to the Gross Motor Function Classification System. To enhance the interpretation of these charts, researchers altered the rate parameters to age-90, the “age in years by which children are expected to reach 90% of their motor development potential.” Smaller values (in years) indicate faster progress toward development limits, and there was a trend for a faster progression to the limit as severity of impairment increased. Researchers caution that “an earlier (younger) age-90 does not indicate ‘better’ developmental progress—only that a child is closer to his/her limit, whatever that limit may be.” The researchers feel that these findings will help parents better understand the outlook for their child’s gross motor function and should provide clinicians and parents with more data to make informed decisions about appropriate therapy goals for their children.

Suggested Reading
Rosenbaum PL, Walter SD, Hanna SE, et al. Prognosis for gross motor function in cerebral palsy: creation of motor development curves. JAMA. 2002;288:1357-1363.

NEUROPSYCHIATRIC SYMPTOMS PREVALENT IN MILD COGNITIVE IMPAIRMENT

Depression, irritability, and apathy are common among people with mild cognitive impairment, according to an article published in the September 28 JAMA. Researchers sought to determine the prevalence of neuropsychiatric symptoms in patients with dementia and mild cognitive impairment, defined as “cognitive impairment in elderly persons not of sufficient severity to qualify for a diagnosis of dementia.” The investigation was a corollary of the Cardiovascular Health Study and the first study to assess the occurrence of neuropsychiatric symptoms in mild cognitive impairment.

From 1991 to 1994, 3,608 participants from the Cardiovascular Health Study received magnetic resonance imaging and completed a Modified Mini-Mental State Examination. Individuals thought to be at high risk for dementia were recruited for neuropsychologic testing; a neurologist or geriatric psychiatrist made an additional evaluation, and an interview with the participant’s proxy was conducted. Of the 3,608 participants, 824 completed the Neuropsychiatric Inventory. Based on this accumulated information, a diagnosis of dementia, mild cognitive impairment, or healthy was made. Three hundred sixty-two of these patients were diagnosed with dementia, while 320 were classified as having mild cognitive impairment.

Researchers reported that almost half the patients with mild cognitive impairment (43.1%) showed neuropsychiatric symptoms, while a minority of patients with dementia (25.4%) were symptom-free. For the participants with dementia, the most frequently observed symptom was apathy (in 36% of the patients), followed by depression and aggression (observed in 32% and 30% of the participants, respectively). Among the participants with mild cognitive impairment, the most common symptom was depression (observed in 20% of the participants), followed by apathy and irritability (both seen in 15% of the participants). The researchers concluded that “mild cognitive impairment may not be a separate category of disturbance, such as age-associated or age-appropriate memory loss, but is rather on a continuum between healthy and dementia.”

Suggested Reading
Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the Cardiovascular Health Study. JAMA. 2002;288:1475-1483.

DRUGS THAT LOWER BLOOD PRESSURE MAY PREVENT DEMENTIA

An extension of the Systolic Hypertension in Europe (Syst-Eur) Study has reinforced the theory that blood pressure–lowering therapy protects against dementia in elderly patients with systolic hypertension. After the Syst-Eur trial ended in 1997, randomized eligible patients were offered active study medication for a further period of observation in the hopes of refining the estimates of the long-term effects of antihypertensive therapy on the incidence of dementia. The study was published in the October 14 Archives of Internal Medicine.

Researchers recruited 2,902 dementia-free patients older than 60 with a sitting systolic blood pressure ranging from 160 to 219 mm Hg. Active treatment consisted of the dihydropyridine calcium channel blocker nitrendipine (10 to 40 mg/d), with the optional addition of enalapril maleate (5 to 20 mg/d), hydrochlorothiazide (12.5 to 25 mg/d), or both drugs; matching placebos were used in a similar way. The medications were titrated or combined to reduce the sitting systolic blood pressure by 20 mm Hg or more. The median follow-up period was 3.9 years.

Using the DSM-III-R and the Mini-Mental State Examination, investigators determined that 64 patients had developed dementia over the course of the study. Of these patients, 41 developed Alzheimer’s disease, 19 had mixed or vascular dementia, and four cases were unable to be determined. Forty-three of the cases of dementia occurred in the control group, while the remaining 21 cases occurred in the group receiving active treatment, showing that the incidence of dementia decreased by 55% with long-term active treatment. Researchers determined that nitrendipine “was associated with a dose-dependent reduction in the probability of dementia” and “the risk declined by approximately 50% for every tablet of 20 mg taken per day.” The investigators concluded by stating that at the rate observed by the study, “treating 1,000 hypertensive patients for five years can prevent 20 cases of dementia.”

NR

Suggested Reading
Forette F, Seux ML, Staessen JA, et al. The prevention of dementia with antihypertensive treatment: new evidence from the Systolic Hypertension in Europe (Syst-Eur) Study. Arch Intern Med. 2002;162:2046-2052.

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