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LITERATURE MONITOR:
RECENT ARTICLES OF INTEREST IN NEUROLOGY
ATHEROSCLEROSIS IS ASSOCIATED WITH AN INCREASED RISK OF DEMENTIA
Atherosclerosis may be involved in the pathogenesis of dementia and Alzheimer’s disease, reported researchers in the May Annals of Neurology. Marieke van Oijen, MD, PhD, and colleagues from the Department of Epidemiology and Biostatics and the Department of Neurology, both at Erasmus Medical Center, Rotterdam, the Netherlands, noted that the association between the disorders may be attenuated in studies with long follow-up periods “due to selective mortality in individuals with severe levels of atherosclerosis.”
The investigative team based their prospective cohort study on the 6,647 participants (mean age at baseline, 69) from the Rotterdam Study who were confirmed as dementia-free at enrollment. Mean baseline common carotid intima media thickness (CIMT) was 0.79 mm, and 41.1% of the cohort was found to have no carotid plaques via B-mode ultrasonography. Mean ankle–brachial index—used as an indicator of peripheral arterial disease—was reported as 1.06.
During a mean follow-up of nine years, 678 participants were identified with incident dementia: 476 patients were diagnosed with Alzheimer’s disease, 52 patients had Alzheimer’s disease and cerebrovascular disease, 78 patients had vascular dementia, and 72 developed dementia due to other causes. The investigators reported that higher common CIMT at baseline was associated with an increased risk of dementia. “Subjects in the fifth quintile had a 50% increased risk for dementia compared with subjects in the first quintile (reference category),” they said. However, this increased risk was restricted to the development of Alzheimer’s disease, and when stratified by time to dementia onset, a borderline significant association was only observed with short follow-up (≤ 5 years).
Based on measurements taken at the third follow-up survey (mean participant age, 72.4), patients in the fifth quintile of common CIMT, compared with the first, had a hazard ratio (HR) of 2.60 for dementia. Participants with five or six carotid plaques also had an increased risk compared with those who had no carotid plaques (HR, 2.64). Subjects with greater changes of common CIMT change between baseline and third follow-up, or who had 1- or 2-point increases in plaque score, also had an increased risk. No significant associations were found with vascular dementia; however, the authors noted that this may have been due to a low number of cases.
“Our findings of an association predominantly with short follow-up only, in combination with evidence from cross-sectional studies, may support the notion that the association between atherosclerosis and dementia is not causal,” reported the authors. The association between common CIMT and dementia remained statistically significant during long follow-up, and the investigators suggested that if those subjects with atherosclerosis who died during follow-up survived, they would have had an increased risk for dementia.
Suggested Reading
van Oijen M, de Jong FJ, Witteman JC, et al. Atherosclerosis and risk for dementia. Ann Neurol. 2007;61(5):403-410.
MYELIN IMAGING STUDY COULD LEAD TO NOVEL MS THERAPIES
Researchers have discovered that calcium ions could play a crucial role in multiple sclerosis (MS) by causing myelin sheath degradation, according to a study published June 5 in the online Journal of Neuroscience Research. These results could lead to novel methods of halting the progression of MS and reversing prior damage.
Yan Fu and colleagues used coherent anti-Stokes Raman scattering (CARS) to examine how the myelin sheath is degraded by lysophosphatidylcholine (LPC). They studied images of healthy and diseased myelin from spinal cord tissues from animals and in the sciatic nerves of living mice and found that cytosolic phospholipase A2 contributes to myelin degradation by turning lipid molecules into LPC, which further degrades the myelin sheath. The researchers’ findings suggest that LPC causes myelin sheath degradation by allowing an influx of calcium ions into the myelin. The increased concentration of calcium ions then would activate two enzymes, calpain and cytosolic phospholipase A2.
Mr. Fu and colleagues posited that LPC-induced calcium influx into cells and cytosolic phospholipase A2 could be causes for nociceptive pain in patients with MS. “It is known that elevation of intracellular calcium activates several protein kinases, such as protein kinase C and calcium/calmodulin-dependent protein kinase II,” the investigators noted. “Activation of these protein kinases leads to the phosphorylation of ionotropic glutamate receptors, increasing synaptic efficacy.” In addition, the research team pointed out that fatty acids and lysophospholipids—often substrates for the synthesis of more potent lipid mediators involved in pain transmission—are generated by cytosolic phospholipase A2’s role in the hydrolysis of neural membrane phospholipids.
Mr. Fu and colleagues posited that LPC-induced calcium influx into cells and cytosolic phospholipase A2 could be causes for nociceptive pain in patients with MS. “It is known that elevation of intracellular calcium activates several protein kinases, such as protein kinase C and calcium/calmodulin-dependent protein kinase II,” the investigators noted. “Activation of these protein kinases leads to the phosphorylation of ionotropic glutamate receptors, increasing synaptic efficacy.” In addition, the research team pointed out that fatty acids and lysophospholipids—often substrates for the synthesis of more potent lipid mediators involved in pain transmission—are generated by cytosolic phospholipase A2’s role in the hydrolysis of neural membrane phospholipids.
“More importantly,” the investigators noted, “CARS microscopy can be applied to examine the mechanisms of inflammation- and trauma-induced myelin damage, which we believe will contribute to a deeper understanding of the pathogenesis of demyelination.”
Suggested Reading
Fu Y, Wang H, Huff TB, et al. Coherent anti-Stokes Raman scattering imaging of myelin degradation reveals a calcium-dependent pathway in lyso-PtdCho-induced demyelination. J Neurosci Res. 2007 June 5; [Epub ahead of print].
IS BENIGN PAROXYSMAL POSITIONAL VERTIGO ASSOCIATED WITH MIGRAINE IN WOMEN?
According to a report published in the July Journal of Neurology, Neurosurgery, and Psychiatry, benign paroxysmal positional vertigo (BPPV) may be the most common vestibular disorder and also may be linked to migraine in women.
From a random telephone survey sample of 4,869 participants, Michael von Brevern, MD, and colleagues gathered data on 1,003 patients with a history of moderate or severe dizziness or vertigo who had undergone neurotological interviews. Of these participants, 243 (24%) had a history of vestibular vertigo, and 80 (8%) fulfilled diagnostic criteria for BPPV. The lifetime, one-year, and four-week prevalence rates of BPPV were 2.4%, 1.6%, and 0.7%, respectively; 3.2% of females and 1.6% of males had a lifetime prevalence of BPP. In addition, the one-year incidence of BPPV was 0.6%.
Medical consultations for vertigo were reported in about 78% of persons with BPPV and hospital admissions for BPPV were reported in 6% of the participants. The median duration of an episode of BPPV was two weeks; 31% of participants reported that their episode lasted longer than one month. Among all patients with BPPV, 86% described their condition as rotational vertigo, and 14% described the condition as a sensation of dizziness, as opposed to an illusion of rotation. All patients experienced BPPV in bed, and the majority (85%) reported that they had the condition while turning over. Among all affected participants, 8% received effective treatment.
“BPPV is likely to be the most common vestibular disease as every third participant with vestibular vertigo had BPPV in our study,” Dr. von Brevern’s research team stated. The investigators also found that the mean age of BPPV onset was 49, and that the condition starts to increase around age 35, according to a calculation of age-related cumulative incidence.
The strongest association for BPPV was with migraine, the researchers found, which could be related to the higher prevalence of BPPV among females. A history of migraine was found in 21% of men and 43% of women with BPPV. “The relationship between migraine and BPPV is poorly understood,” the researchers stated. “It has been speculated that migraine could cause vasospasm of the labyrinthine arteries, leading to detachment of otoconia from the utricular macula.”
Dr. von Brevern and colleagues noted, “Taking into account our sample size and the confidence interval for the adjusted odds ratio, we conclude that the female preponderance in BPPV reflects to a considerable extent an association of migraine and BPPV but we cannot exclude an additional independent association of female sex and BPPV.”
In an accompanying editorial, Helen S. Cohen, EdD, stated, “Many women do not have migraine but do have BPPV, so other factors are probably involved. Further research is needed to learn why it is more common in women and to elucidate the relationship among comorbid factors and BPPV.”
Suggested Reading
von Brevern M, Radtke A, Lezius F, et al. Epidemiology of benign paroxysmal positional vertigo: a population based study. J Neurol Neurosurg Psychiatry. 2007;78(7):710-715.
Cohen HS. New epidemiological findings on benign paroxysmal positional vertigo. J Neurol Neurosurg Psychiatry. 2007;78(7):663.
PATIENTS WITH DEMENTIA CAN DRIVE SAFELY UP TO THREE YEARS AFTER DIAGNOSIS
A clinical review published in the June 30 British Medical Journal has found that older persons with early dementia should be capable of safe driving. Dr. David A. Breen and colleagues conducted a literature search of electronic databases limited to studies on vehicular crash risk in patients with Alzheimer’s disease and other dementias, and found that the risk of crashes in dementia patients is acceptably low for up to three years after diagnosis.
“The risk of crashes in patients with dementia has been extensively studied,” Dr. Breen and colleagues noted. “Over the course of the disease evidence suggests that the risk of a crash is significantly increased. As a general rule, however, the risk seems to remain acceptably low for up to three years after the onset of dementia, by which time most patients have stopped driving.”
In one of the retrospective case-control studies included for review, 130 patients with possible or probable Alzheimer’s disease were matched with 112 controls. Although a significant increase in crash rate was observed among patients with possible or probable Alzheimer’s disease during the entire course of the illness compared with controls, the crash risk increased linearly after roughly the third year that the illness was clinically apparent.
“It is important to advise patients and their families on an individual basis of the predicted decline in driving ability, although three years from when the disease becomes clinically obvious may be reasonable,” Dr. Breen and colleagues stated. “This allows patients to plan for when they stop driving and to look for alternative transport options. This in itself is a compelling reason to share the diagnosis of dementia with a patient who drives. Many older people do not, however, consider public transport to be adequate or efficient and often see it as a threat to their security.”
The investigators also recommended that clinicians ask family and friends of their patients about specific driving behaviors that indicate signs of incompetence, such as miscalculating speed and distances or driving the wrong way around roundabouts and getting lost in familiar areas.
“Family members can help patients realize that it is no longer safe for them to drive,” they noted. “But family may also have ulterior motives for maximizing or, more usually, minimizing driving difficulties, of which clinicians should be aware.”
Suggested Reading
Breen DA, Breen BP, Moore JW, et al. Driving and dementia. BMJ. 2007; 334(7608):1365-1369.
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Suggested Reading
1. Rachelefsky GS, Shapiro GG, Bergman D, et al. Pediatric Asthma: Promoting Best Practice. 1999. Milwaukee, Wis: American Academy of Allergy, Asthma & Immunology Inc; 1999.
2. Mannino DM, Homa DM, Pertowski CA, et al. Surveillance for asthma-United States, 1960-1995. Mor Mortal Wkly Rep CDC Surveill Summ.1998;47:1-27.
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Suggested Reading
1. Rachelefsky GS, Shapiro GG, Bergman D, et al. Pediatric Asthma: Promoting Best Practice. 1999. Milwaukee, Wis: American Academy of Allergy, Asthma & Immunology Inc; 1999.
2. Mannino DM, Homa DM, Pertowski CA, et al. Surveillance for asthma-United States, 1960-1995. Mor Mortal Wkly Rep CDC Surveill Summ.1998;47:1-27.
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Suggested Reading
1. Rachelefsky GS, Shapiro GG, Bergman D, et al. Pediatric Asthma: Promoting Best Practice. 1999. Milwaukee, Wis: American Academy of Allergy, Asthma & Immunology Inc; 1999.
2. Mannino DM, Homa DM, Pertowski CA, et al. Surveillance for asthma-United States, 1960-1995. Mor Mortal Wkly Rep CDC Surveill Summ.1998;47:1-27.
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Suggested Reading
1. Rachelefsky GS, Shapiro GG, Bergman D, et al. Pediatric Asthma: Promoting Best Practice. 1999. Milwaukee, Wis: American Academy of Allergy, Asthma & Immunology Inc; 1999.
2. Mannino DM, Homa DM, Pertowski CA, et al. Surveillance for asthma-United States, 1960-1995. Mor Mortal Wkly Rep CDC Surveill Summ.1998;47:1-27.
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