Idiopathic rapid eye movement sleep behavior disorder (RBD) may be the initial manifestation of the synucleinopathies Parkinson's disease (PD), dementia with Lewy bodies (DLB), and multiple system atrophy (MSA), occurring some 50 years before the neurodegenerative syndrome clinically manifests, a new study suggests.

This finding has "important implications for epidemiologic studies and future interventions designed to slow or halt the neurodegenerative process," as per Bradley F. Boeve, MD, and colleagues from the Department of Neurology at the Mayo Clinic College of Medicine in Rochester, Minnesota.

Their results are published online July 28 in the journal Neurology .

Using the Mayo Clinic Medical Records Linkage System, the researchers identified 550 patients with idiopathic RBD and a synucleinopathy. Twenty-seven (4.9%) of these patients met the study criterion of isolated RBD predating by more than 15 years the onset of PD, PD dementia (PDD), DLB, or MSA. Twenty-four (89%) of the 27 patients were male.

The interval between RBD and subsequent neurodegenerative syndrome ranged up to 50 years, with a median interval of 25 years. The median age at onset of RBD was 49 years (range, 21 – 60 years), and the median age at onset of neurologic symptoms was 72 years (range, 51 – 80 years).

At initial onset, primary motor symptoms were seen in 13 patients — 9 with PD, 3 with PD and mild cognitive impairment (MCI), and 1 with PDD, whereas primary cognitive symptoms occurred in 13 patients — 10 with probable DLB and 3 with MCI. One patient presented with primary autonomic symptoms and was diagnosed as having MSA.

At the most recent follow-up, 63% of study subjects had progressed to dementia (PDD or DLB), and concomitant autonomic dysfunction was confirmed in 74% of all patients.

The Mayo Clinic study, he and colleagues note in their editorial, confirms "one of the most interesting mysteries — the overwhelming male predominance (89% in this study) of those with RBD who develop a neurodegenerative process, which is not male-predominant." The reasons for this are unknown. Hormonal studies have not implicated androgenic hormones.

The finding that RBD may be a very early warning sign of neurodegenerative disease has important implications for treatment, Dr. Mahowald said, given "exciting new treatments" for PD that are on the horizon, such as gene therapy and cell replacement therapy.

"But the sad fact is that by the time Parkinson's disease becomes clinically apparent there has been widespread damage in the central nervous system that has probably been going on for decades," Dr. Mahowald said. "We have to come up with an extremely early marker for Parkinson's disease if these new therapies are going to work, otherwise the horse is out of the barn. Idiopathic RBD may absolutely be such a marker," he predicted.

Ref: Neurology. 2010;75:488-489, 494-499.

In the first longitudinal analysis of its kind, investigators have identified a link between vitamin D and Parkinson's disease. Using a cohort of more than 3000 people, researchers found that low vitamin D levels increased the risk for Parkinson's, and high rates appeared to have a protective effect.

The preliminary findings appear in the July issue of the Archives of Neurology .

This study was carried out in Finland, an area with restricted sunlight exposure. It is a population that typically has low vitamin D levels. The mean serum level was about 50% of the suggested optimal level of 75 to 80 nmol/L.

To investigate the possible association between vitamin D and Parkinson's, researchers led by Paul Knekt, DPH, from the National Institute for Health and Welfare in Helsinki, Finland, studied a large cohort from the Mini-Finland Health Survey, drawn from the population register. During the 29-year follow-up period, there were 50 incident cases of Parkinson's disease.

Researchers determined serum 25-hydroxyvitamin D levels using frozen samples stored at baseline. They estimated the relationship between vitamin D concentration and Parkinson's disease using a Cox model.

The investigators found that individuals with a serum vitamin D concentration of at least 50 nmol/L had a 65% lower risk for Parkinson's than those with values less than 25 nmol/L after adjustment for several potential confounders. The relative risk between the highest and lowest vitamin D levels was 0.35 (95% confidence interval, 0.15 - 0.81; P = .006).

Despite the overall low vitamin D levels in the study population, the researchers also identified a dose-response relationship.

The exact mechanisms by which vitamin D may protect against Parkinson's disease are not fully understood. Vitamin D has, however, been shown to exhibit neuroprotective effects through antioxidative mechanisms, neuronal calcium regulation, immunomodulation, enhanced nerve conduction, and detoxification mechanisms.

The investigators acknowledge the finding could be a result of residual confounding, and further studies are needed.

Ref: Arch Neurol . 2010;67:808-811.

Continuing antihypertensive medication after a stroke does not appear to reduce 2-week death or dependency, cardiovascular event rate, or mortality at 6 months, according to new research.

Thompson G. Robinson, MD, published the findings of a randomized study — Continue Or Stop post-Stroke Antihypertensives Collaborative Study (COSSACS) — online July 12 in Lancet Neurology .

The study sought to assess the efficacy and safety of continuing or stopping preexisting antihypertensive drugs within 48 hours of when a patient had undergone nondysphagic, ischemic, or hemorrhagic stroke, and within 48 hours of the last dose of antihypertensive drugs.

A spontaneous decrease in blood pressure usually occurs 4 to 10 days after stroke, but substantial reductions in blood pressure can be associated with cerebral hypoperfusion as a consequence of poststroke cerebral dysautoregulation.

The prospective trial included patients from 49 participating UK National Institute for Health Research Stroke Research Network centers from January 1, 2003, to March 31, 2009.

Patients were randomly assigned to either continue (n = 379) or stop (n = 384) preexisting antihypertensive drugs for 2 weeks after their stroke. Of the patients who continued antihypertensive drugs, 72 of 379 reached the primary endpoint (death or dependency [modified Rankin scale score ≥ 3 points] at 2 weeks) compared with 82 of 384 patients in the stop group, which was not a significant difference between groups ( P = .3).

The difference between the 2 groups in systolic blood pressure at 2 weeks was 13 mm Hg (95% confidence interval, 10 - 17 mm Hg), and the difference in diastolic blood pressure was 8 mm Hg (95% confidence interval, 6 - 10 mm Hg; P < .0001).

The incidences of serious adverse events, 6-month mortality, and major cardiovascular events were similar between groups.

According to the researchers, a post hoc analysis found that continuing antihypertensive drugs might be associated with reduced 2-week death and dependency in patients with ischemic stroke confirmed on neuroimaging. "However, this post-hoc subgroup analysis requires further evaluation in patient populations with well-defined stroke subtypes," they write.

The findings add to an emerging consistent message: oral antihypertensive treatment can be used safely in nearly all patients within the first few days of mildly disabling or non-disabling stroke or transient ischaemic attack because of the modest size (about 6–12 mm Hg systolic) and speed (several hours) of the blood-pressure reduction.

Ref: Lancet Neurol . Published online July 12, 2010.

The risk for psychiatric illness is significantly higher in young adults exposed to cigarette smoke in the womb relative to those without prenatal cigarette smoke exposure, even after adjusting for maternal psychiatric illness and other confounding factors, according to a Finnish study reported in the August issue of the Archives of General Psychiatry .

Prenatal smoking exposure impairs fetal growth and modulates brain development, which may alter mental development of the offspring, they point out.

The researchers used population-based, longitudinal registry data to evaluate the effects of prenatal smoking exposure on psychiatric morbidity among 175,869 Finnish young adults born from January 1, 1987, through December 31, 1989, with follow-up lasting 18 to 20 years. They had information on mothers' smoking habits (self-reported) during pregnancy and other relevant background factors, as well as psychiatric history of mothers and offspring.

Smoking during pregnancy was reported by 26,075 mothers (15.3%). Of these, 8866 (34.0%) smoked more than 10 cigarettes a day. In 5487 children (3.2%), maternal smoking history was unknown.

The prevalence of any psychiatric diagnosis was 15.0% after excluding the children with unknown maternal smoking history. The prevalence was 13.7% in unexposed children (the reference group), 21.0% in those exposed to fewer than 10 cigarettes a day (adjusted odds ratio [aOR], 1.53; 95% confidence interval [CI], 1.47 – 1.60), and 24.7% in those exposed to more than 10 cigarettes a day (aOR, 1.85; 95% CI, 1.74 – 1.96).

Prenatal smoke exposure significantly increased the risk for most of the psychiatric diagnoses, with the exception of schizophrenia and anorexia diagnoses, the study authors report. The strongest effects were seen for psychiatric disorders due to psychoactive substance use and behavioral and emotional disorders. The lack of a statistically significant finding for schizophrenia may be due to a fairly low number of cases in the study.

There were 870 total deaths in the study population (5.7 per 1000), of which 64 (7.4%) were suicides (excluding children with unknown maternal smoking data). After adjusting for confounding factors, young adults exposed to >10 cigarettes a day during gestation had a significantly increased risk for early death (OR, 1.69; 95% CI, 1.31 – 2.19) compared with unexposed young adults. The mortality rate per 1000 children was 4.7 for unexposed children vs 6.3 and 9.1 for exposure to <10 and >10 cigarettes per day, respectively.

"The study," Dr. Fergusson noted, "adds to previous research by being based on a large population (but) is limited by the use of official record data."

The control of confounding factors is "limited," he added, "raising the possibility that the findings may reflect the presence of other factors, which are associated with pregnancy smoking. A further limitation is that the mechanisms by which pregnancy smoking may lead to increased risks of a wide range of mental disorders are by no means clear."

Nonetheless, Dr. Fergusson said this new study further reinforces public health messages regarding the adverse effects of smoking during pregnancy. "It is well known that pregnancy smoking increases the risk of miscarriage, stillbirth, and low-birth-weight infants. The present findings raise the possibility that exposure to pregnancy smoking may have adverse effects on longer-term mental health of offspring," he noted.

Ref: Arch Gen Psychiatry. 2010;67:841-849.