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Wednesday, April 15, 2015




A study published in the April 15 online edition of JAMA Psychiatry offers new evidence to support a link between diabetes mellitus and depression and later dementia. The authors reported that people who developed both depression and type 2 diabetes had an associated 117 percent higher risk for dementia compared with people with neither condition.


For the study, researchers in Denmark and the US looked at a database of more than 2.4 million Danish citizens who were at least 50 years old and free from dementia at baseline. They collected follow-up data between 2007 and 2013. Overall, 477,133 individuals (or 19.4 percent) had a diagnosis of depression, 223,174 (9.1 percent) had type 2 diabetes, and 95,691 (3.9 percent) had both conditions.


During the study period, 59,663 people (or 2.4 percent of the study population) developed dementia; among them, 15,729 people (26.4 percent) had depression, 6,466 (10.8 percent) had type 2 diabetes, and 4,022 (6.7 percent) had both conditions.


The researchers found that having type 2 diabetes was associated with a 20 percent greater risk for dementia (adjusted hazard ratio [HR] 1.20; 95% CI, 1.17-1.23), and depression was linked to an 83 percent higher risk (HR 1.83; 95% CI, 1.80-1.87) compared with people with neither condition. Having both conditions was associated with a 117 percent greater dementia risk (HR 2.17; 95% CI, 2.10-2.24), and patients younger than 65 with both conditions had a still-greater risk (HR 4.84; 95% CI, 4.21-5.55)


“The combined effect of both disorders appeared more than additive, especially among younger persons,” the study authors wrote. “Among those with comorbid depression and DM [diabetes mellitus] in our cohort, 6% of incident dementia may be accounted for by the interaction between depression and DM overall, and 25% may be accounted for among those younger than 65 years.”


“Given that depression in patients with DM is associated with poor self-care, non-adherence to treatment regimens, and adverse psychobiological changes, this younger group with comorbid depression and DM may be vulnerable to developing dementia later in life,” they noted.  


Adequate screening and treatment of both depression and diabetes throughout a person’s lifetime could play a large role in reducing their risk for later dementia, and potentially for reducing the public health burden of dementia worldwide, the researchers wrote.


“The co-occurrence of diabetes mellitus and depression, especially in persons younger than 65 years, poses an important hazard to healthy brain aging and cognitive fitness in the later years of life,” Charles F. Reynolds, III, MD, UPMC endowed professor of geriatric psychiatry and a professor of neurology, behavioral and community health sciences, and clinical and translational science at the University of Pittsburgh, wrote in an invited commentary. The findings underscore the importance of interventions aimed at reducing depression, diabetes, and dementia through lifestyle modifications such as diet, exercise, and pharmacologic management of medical conditions, he said.


“The convergence of expertise from epidemiology, behavioral and basic science in the biology of aging, and brain health are all necessary to ‘move the needle’ in the demographic challenge that confronts the entire globe,” Dr. Reynolds said.


For more coverage of the link between depression, diabetes, and dementia, browse our archives here.

Tuesday, April 14, 2015




Hospital costs for stroke patients admitted with atrial fibrillation are 20 percent higher on average than they are for those without afib, according to a new cost analysis from the US Centers for Disease Control and Prevention (CDC). The study is one of the first to look at the financial burden of atrial fibrillation in stroke-related hospitalizations.


The study, published in the April 9 online edition of Stroke, underscores the need for interventions to reduce the burden of atrial fibrillation in the population, particularly among patients aged 18 to 54, who were found to have the highest stroke-related hospital admissions costs, the researchers wrote. Atrial fibrillation is associated with a four to five-fold risk for stroke, as well as a higher risk of more severe strokes, recurrent strokes, and stroke-related mortality, they noted.


For the study, the researchers analyzed hospital inpatient data collected between 2010 and 2012 in the MarketScan Claims and Encounters database, which contains information on drug and medical insurance claims from approximately 138 million de-identified patients in the US. The researchers identified 33,500 hospital admissions for first stroke in adults aged 18 to 64, including 2,407 patients (7.2 percent) with atrial fibrillation, as well as 6,582 admissions for recurrent strokes, including 397 patients (6 percent) with afib.


Patients with atrial fibrillation tended to have longer hospital stays, Guijing Wang, PhD, a medical economist with the CDC’s Division for Heart Disease and Stroke Prevention, and colleagues found; 42.9 percent of non-repeat stroke patients with afib had stays of five days or more, compared with 26.4 percent among patients without afib (p<0.001).


Admissions for stroke patients with atrial fibrillation also cost $4,991 more on average than those for patients without afib — $23,770 versus $18,779, the researchers reported. They calculated the additional afib-related costs for non-repeat stroke admissions to be $4,905, or 20.6 percent of the total hospitalization costs (p<0.001). There was also a trend toward higher costs among recurrent stroke patients with afib, although the trend did not reach statistical significance (p<0.341).


The researchers also conducted a separate analysis for patients aged 18 to 54 and 55 to 64, finding that the average cost of admissions for stroke patients with afib was $5,084 higher than patients without afib (p<0.001) among those aged 18 to 54, compared with $4,854 among those aged 55 to 64 (p<0.001).


Having atrial fibrillation significantly increased costs associated with recurrent stroke stroke only among patients aged 55 to 64, with an average cost increase of $3,537 (p<0.005). Costs did not differ significantly by sex across the board.


Given the results, interventions aimed at managing and preventing stroke and atrial fibrillation among this younger segment of patients may be beneficial, the authors wrote, and should guide future policymaking and economic research. “Although research and public health efforts have focused on stroke management and prevention among those aged ≥ 65 years, stroke interventions such as AFib management among younger adults, as well as older adults, may have a great economic impact.”


For more coverage of atrial fibrillation and stroke, browse our archives here.


Image via Lisa Yarost on Flickr.

Friday, April 10, 2015



The migraine drug sumatriptan may be less effective at treating migraine with aura compared with migraine without aura, according to new research published in the April 3 online edition of Neurology.


For the study, Jakob Møller Hansen, MD, PhD, of Glostrup Hospital at the University of Copenhagen in Denmark, and colleagues pooled outcomes data from 21 double-blind trials of sumatriptan for migraine involving 3,714 patients: 2,568 received 100 mg of sumatriptan and 1,146 received placebo. Among them, 1,091 experienced migraine with aura and 2,336 experienced migraine without aura.


The researchers found that pooled pain-free rates — defined as a reduction of moderate or severe migraine pain to no pain — at two hours after taking 100 mg of sumatriptan were significantly higher for patients without aura: 32 percent compared with 24 percent for patients experiencing migraine with aura (p<0.001). Pain freedom rates at two hours in patients experiencing attacks with aura were lower regardless of the pre-treatment headache severity, the authors noted.


The findings suggest that “migraine attacks with aura are less responsive to sumatriptan than migraine without aura,” the authors wrote. “One possible explanation for this differential response to sumatriptan is that migraine attacks that include cortical symptoms may involve more diffuse or severe derangements of brain pathology, and thus may be more difficult to treat. Alternatively, attacks of migraine with aura may involve distinct mechanisms that result in different responses to therapy.”


Given these results, they said, future studies of migraine treatments should offer separate analyses of both migraine diagnosis and the individual attacks, as these factors may influence results. Many migraine patients may experience attacks with and without aura, they noted.


Dr. Hansen and colleagues also looked at similar outcomes data from a single randomized, controlled study of inhaled dihydroergotamine (DHF) in 903 patients with or without aura. (This formulation is currently not approved for clinical use in the United States, noted Thomas N. Ward, MD, a professor of neurology at the Geisel School of Medicine at Dartmouth in Hanover, NH, in an accompanying editorial.) Their analysis revealed no significant differences in two-hour pain-free rates for patients experiencing attacks with and without aura (27.2 percent compared with 29.4 percent; p=0.65).


The fact that inhaled DHF showed different outcomes than sumatriptan was not surprising, Dr. Ward commented. “As a clinician, I would expect inhaled dihydroergotamine, which bypasses the gastrointestinal tract, to be more reliable, consistent, and efficacious in a migraineur with nausea or vomiting.” But comparing two treatment results from two very different agents is problematic, he added.


Overall, the study raises a number of interesting questions, Dr. Ward said. Among them: “Does this suggest that attacks of migraine with aura are more severe and therefore harder to treat effectively? Does it mean, as the authors wonder, that attacks of migraine with aura have a markedly different pathophysiology than attacks without aura and therefore respond to (some) treatments differently?


He concluded, “The authors should be commended for attempting to use a common clinical symptom as a prognostic guide and for opening up a new line of inquiry as to how the presence or absence of aura affects treatment of migraineurs.”


For more coverage of acute therapy for migraine, browse our archives here.

Wednesday, April 08, 2015



The American Academy of Neurology has released a comprehensive new guideline recommending a multidisciplinary team approach in evaluating, diagnosing, and managing congenital muscular dystrophy (CMD). The American Association of Neuromuscular & Electrodiagnostic Medicine (AANEM) Practice Issues Review Panel and the AAN Guideline Development Subcommittee jointly developed the evidence-based guideline.


The recommendations, published in the March 31 edition of Neurology, reflect the best evidence in the medical literature as defined by the AAN classification of evidence system, which rates studies as Class I, II, III, or IV based on methodology and trial type, among other factors.


Leslie Morrison, MD, a professor of neurology and pediatrics at the University of New Mexico Health Science Center in Albuquerque, discussed the findings and the supporting evidence in a telephone interview with Neurology Today.


Congenital muscular dystrophy in a three-year-old, showing flexed and abducted hips that are externally rotated with moderate knee-flexion contractures. Image from Weinstein SL, Flynn JM, Lovell and Winter’s Pediatric Orthopaedics. LWW 2013.



Due to the range of symptoms associated with CMDs, we found that it takes experienced multidisciplinary teams to coordinate care for these patients. Even so, there is a paucity of good evidence available to rate the efficacy of various treatment interventions.


There are a number of CMD subtypes, some of which appear to occur in certain specific geographic locations and/or involve children from different ethnic backgrounds. Although children anywhere can be born with the disease, certain mutations have been linked to clusters in Japanese, Korean, and Ashkenazi Jewish populations, as well as in Turkish infants. We believe that other founder mutations are likely to exist. This is especially true in Japan, where one particular form of CMD is prevalent and severe.


There are also specific patterns of muscle weakness and problems with mobility once children become toddlers. Blood testing is helpful in detecting increased levels of creatine kinase (CK) in some but not all children with CMD.



In general, we found that progressive skeletal muscle weakness and hypotonia are the cardinal primary early manifestations. One Class II study and one Class III study demonstrated that distal joint hyperlaxity, congenital hypotonia, and joint contractures may be characteristic of collagenopathy, a rare inherited disorder of connective tissue in the spine and skeleton.


Also, serum CK levels are typically but not always elevated. There is also evidence that confirms congenital weakness in infants with CMDs, as well as elevated serum CK levels and abnormal white matter signaling on magnetic resonance imaging (MRI), which may help predict severe weakness of the trunk and limbs and hypotonia at birth. One Class II study showed that congenital weakness, elevated serum CK levels, and white matter signal abnormalities on brain MRI predict the merosinopathy subtype.


Classic patterns of muscle weakness, structural eye abnormalities, and cortical brain abnormalities can predict mutations in known genes for patients with dystroglycanopathies — muscular dystrophies that are associated with aberrant glycosylation of alpha-dystroglycan. This is supported by several Class III studies.



Some children exhibit symptoms at birth while others may not have them until later. Infants with CMD tend to be very sick. With the youngest, there may be eye components and abnormal brain activity, including seizures, for which MRI is very useful, as well as cardiac symptoms. But because many children are asymptomatic until they are older, cardiac symptoms can be difficult to assess because these kids do not usually complain about chest pain or rhythm problems.



A broad range of complications involving multiple organ systems have been reported in the literature, but these often have delayed onset. They can include cardiac and respiratory symptoms, swallowing difficulties, and muscle problems, as well as effects on the central nervous system, scoliosis, and a breakdown of skin tissue. This is one reason why such children should be referred to multidisciplinary specialty clinics.


One Class II article found that 58 percent of patients with CMD had cognitive impairment, while a Class III paper reported a high incidence of seizures in Japanese children with Fukuyama CMD. One Class II study reported respiratory complications in 12 percent of patients, which is why supplementary oxygen may be required.



Physical therapy can help, and nutrition is very important. One Class III study of spinal fusion found that correction and prevention of progression of scoliosis and pelvic obliquity over two years resulted in improved or stable balance and sitting posture. Aside from supplementary oxygen, if needed, the impact of specific treatments on respiratory status and other complications requires further research.


Look for the full interview in the April 16 issue of Neurology Now. For more coverage of congenital muscular dystrophy, browse our archives here.

Tuesday, April 07, 2015




Two targeted temperature management strategies proved equally effective in sustaining quality of life and cognitive function following cardiac arrest, according to clinical trial results published in the April 6 online edition of JAMA Neurology.


The study compared mild cooling regimens of 33 degrees Celsius (91.4 degrees Fahrenheit) and 36°C (96.8°F) to prevent brain injury — the primary cause of death for patients treated in intensive care units following cardiac arrest outside the hospital — in 939 patients between November 2010 and January 2013; 473 were assigned to a target temperature of 33°C and 466 to 36°C. The treatment lasted 36 hours.


The researchers, led by Niklas Nielsen, MD, PhD, a consultant in intensive care medicine in the department of anesthesia and intensive care at Lund University and Helsingborg Hospital in Sweden, assessed patients’ cognitive function and quality of life at six months post-cardiac arrest. They assessed cognitive function using the Mini-Mental State Examination (MMSE) and asked observers to respond to the Informant Questionnaire on Cognitive Decline in the Elderly (IQCODE). In addition, the research team asked patients to report on their perceived quality of life and mental recovery.


Among the findings, 245 patients in the 33°C group were alive at six months, compared with 246 in the 36°C group. Scores of cognitive function were similar for both groups, with a median MMSE score of 28 among survivors (p=0.61). The median IQCODE score was 79.5 in the 33°C degrees group compared with 80.7 in the 36°C group (p=0.04); both scores indicated minor cognitive deficits. In the 33°C group, 46 patients (18.8 percent) reported an increased need for help in activities of daily living, compared with 43 (17.5 percent) in the 36°C group (p=0.71). For self-reported cognitive function, 66.5 percent of patients in the 33°C group and 61.8 percent in the 36°C group reported making a full mental recovery (p=0.32).


Severe neurologic impairment and disability in long-term cardiac arrest survivors is rare, and quality of life has been reported to be similar to that of the general population, Dr. Nielsen and colleagues reported. Still, they said, cognitive impairment has been detected in as many as half of all cardiac arrest survivors, and the current study further suggests that patients experience persistent cognitive issues not captured by standard neuropsychological measurements.


“Most survivors reported that they were independent in their daily activities, but one-third stated that they had not made a complete mental recovery after CA [cardiac arrest],” they wrote. “This finding was supported by the report of a relative or close acquaintance, observing a minor decline by IQCODE in half of the survivors and a moderate or severe decline in a quarter.”


This decline may explain why less than half of the patients in both groups returned to their previous level of employment, they said.


“As we move forward and focus on cognitive outcome, we must identify, refine, and validate more sensitive measures and apply them in a standardized format,” wrote Venkatesh Aiyagari, MD, MBBS, a professor of neurological surgery, neurology and neurotherapeutics at the University of Texas Southwestern Medical Center, and Michael N. Diringer, MD, a professor of neurology and neurosurgery and section chief of neurological critical care at Washington University School of Medicine in St. Louis, in an accompanying editorial.


They noted that the study did not provide evidence of superiority for one of the two temperature targets at six months. “Thus, although temperature management after CA significantly improves survival, a lower temperature target does not seem to translate to better cognitive outcomes,” they wrote. “Whether there are certain subgroups that may benefit from the lower temperature target remains to be seen.”


“An important take-home message from this study is that although cognitive changes are common, the overall long-term outcome of patients with a CA who survive to hospital discharge is quite good,” they added.


Dr. Nielsen and colleagues plan to conduct an additional substudy of memory, attention, executive function, anxiety and depression, degree of participation in society, and caregiver outcomes among patients from the two intervention groups, with a matched control group of heart attack patients treated with emergency percutaneous coronary revascularization. This substudy, Dr. Aiyagari and Dr. Diringer wrote, should “shed further light on outcomes after CA survival and may help design a comprehensive battery of tests that could be used in future studies.”


For more coverage of temperature management as a neuroprotective measure, browse our archives here.


Image via on Flickr.