• Many Methods to Prevent Cognitive Decline Fall Short
• Nonceliac Gluten Sensitivity Attributed to Fructan, Not Gluten
• Proinflammatory Diets Tied to Increased Risk for Colorectal Cancer
• 2017–18 Seasonal Influenza Vaccine Effectiveness: Interim Data
• Nonpharmacologic Treatment of Chronic Pain in Disadvantaged Patients
• Supplemental Calcium or Vitamin D Doesn't Lower Fracture Risk in
Community-Dwelling Adults
• Migraine Is Associated with Excess Stroke and Venous Thromboembolism Risk
• Risks and Benefits of Supplemental Breast MRI vs. Screening Mammography
• What Explains the Recent Plateau in Hip Fracture Incidence Among U.S. Women?
• Making Good Use of Antihypertensive Medications for Preeclampsia
• Compression Stockings to Prevent Post-Thrombotic Syndrome
• Does Solanezumab Slow Cognitive Decline in Alzheimer Disease?
Ann Intern Med 2018 Jan 2; 168:30
Many Methods to Prevent Cognitive Decline Fall Short
Individual pharmacologic interventions, cognitive training, or physical activities are not enough for the prevention of cognitive decline, a set of systematic reviews shows.
A series of systematic reviews commissioned by the National Institute on Aging evaluated the association between various interventions and prevention of cognitive decline, mild cognitive impairment (MCI), or Alzheimer dementia. Findings were as follows:
Physical activity (16 trials): There was insufficient evidence that single-component physical activity (aerobic training, resistance training, or tai chi) prevents cognitive decline and dementia in initially nondemented adults. Infour trials, physical activity with multiple components that included flexibility, strength training, balance, endurance, and aerobic training also had no effect on cognitive performance. In one large trial, a multidomain intervention with physical activity, diet, and cognitive training improved cognitive performance and delayed cognitive decline but did not include incident MCI or dementia outcomes.
Pharmacologic Interventions (51 trials): Interventions included medications for dementia, hypertension, and diabetes as well as anti-inflammatory, hormonal, and lipid-lowering agents. Given mixed results, there was not enough evidence to support use of pharmacologic interventions to prevent cognitive decline, MCI, or dementia. Hormonal treatments and raloxifene increased the risk for thrombotic events.
Over-the-Counter Supplements (38 trials): Interventions included omega-3 fatty acids, soy, ginkgo biloba, B vitamins, vitamin D with calcium, vitamin E, vitamin C or β-carotene, and multi-ingredient supplements. There was insufficient evidence that over-the-counter supplements prevent cognitive decline, MCI, or Alzheimer dementia.
Cognitive Training (11 trials): Interventions tested in cognitively normal older adults were computer-based. Cognitive training improved cognitive performance in the specific domain trained. Interventions for those with MCI, provided in small group sessions, showed no significant improvement or mixed results in cognitive performance. There was insufficient evidence for any of these interventions to prevent or delay cognitive decline.
COMMENT: Currently no single intervention has been shown to prevent cognitive decline, MCI, or dementia. A multidomain lifestyle intervention with physical activity, diet, and cognitive training shows promise and supports a comprehensive approach to optimize brain health (NEJM JW Neurol Jan 2018). However, the results need replication and an assessment of whether such intervention decreases risk for incident MCI and dementia. Longitudinal studies that include Alzheimer disease biomarkers may further inform whether these interventions may affect the neurodegenerative process.
CITATION(S):
Brasure M et al. Physical activity interventions in preventing cognitive decline and Alzheimer-type dementia: A systematic review. Ann Intern Med 2018 Jan 2; 168:30.
(http://dx.doi.org/10.7326/M17-1528)
Fink HA et al. Pharmacologic interventions to prevent cognitive decline, mild cognitive impairment, and clinical Alzheimer-type dementia: A systematic review. Ann Intern Med 2018 Jan 2; 168:39.
(http://dx.doi.org/10.7326/M17-1529)
Butler M et al. Over-the-counter supplement interventions to prevent cognitive decline, mild cognitive impairment, and clinical Alzheimer-type dementia: A systematic review. Ann Intern Med 2018 Jan 2; 168:52.
(http://dx.doi.org/10.7326/M17-1530)
Butler M et al. Does cognitive training prevent cognitive decline? A systematic review. Ann Intern Med 2018 Jan 2; 168:63.
(http://dx.doi.org/10.7326/M17-1531)
Larson EB. Prevention of late-life dementia: No magic bullet. Ann Intern Med 2018 Jan 2; 168:77.
(http://dx.doi.org/10.7326/M17-3026)
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Gastroenterology 2018 Feb; 154:529
Nonceliac Gluten Sensitivity Attributed to Fructan, Not Gluten
In those with incomplete symptom relief on a gluten-free diet, clinicians might recommend a low-FODMAP diet.
Many persons without celiac disease develop abdominal symptoms and sometimes nonspecific extra-abdominal symptoms after gluten ingestion.
In a double-blind, crossover study, researchers randomized 59 people with convincingly excluded celiac disease and wheat allergy to consume a gluten-free, low-FODMAP (fermentable oligo-, di-, and monosaccharides and polyols) muesli bar containing either added gluten (2.1 g) or fructan (5.7 g), or with nothing added (placebo), once daily for 7 days. Participants crossed over to the other conditions, eventually consuming all three bars. All participants were normally asymptomatic on a gluten-free diet to which they had adhered for 6 months. Irritable bowel syndrome (IBS) scores, both overall and for bloating, were higher with fructans compared with gluten but not placebo and were not different between gluten and placebo. The fructans group also had worse scores for vitality and weakness compared with the gluten group.
COMMENT: In practice, many clinicians advise patients without celiac disease or wheat allergy who have irritable bowel symptoms, chronic fatigue or weakness, or certain inflammatory conditions, to trial a gluten-free diet. Although a gluten-free diet is generally healthy, some evidence suggests that reduction of whole grains could increase the risk for cardiovascular disease. The current findings suggest that IBS symptoms, including bloating, and some systemic symptoms in patients who believe they are sensitive to gluten, result from fructans in gluten-containing foods and not from gluten itself. Since fructans are in the FODMAP family, a low-FODMAP diet may be a more sensible instruction, particularly for those who want to pursue some gluten ingestion. Also, some patients with gluten sensitivity have incomplete relief of symptoms on a gluten-free diet, perhaps because of continued FODMAP ingestion in other food groups. A low-FODMAP diet is fairly restrictive, and patients who respond to low FODMAP can be encouraged to resume eating FODMAP-containing foods in a controlled fashion, often best done with the assistance of a dietician.
CITATION(S): Skodje GI et al. Fructan, rather than gluten, induces symptoms in patients with self-reported non-celiac gluten sensitivity. Gastroenterology 2018 Feb; 154:529.
(https://doi.org/10.1053/j.gastro.2017.10.040)
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Proinflammatory Diets Tied to Increased Risk for Colorectal Cancer
By Amy Orciari Herman
Patients may ask about a study suggesting that diets with a high potential to cause inflammation are associated with increased risk for colorectal cancer. The findings appear in JAMA Oncology.
Researchers calculated proinflammatory dietary scores for 121,000 U.S. health professionals who regularly completed food-frequency questionnaires as part of two prospective studies. The scores identified diets most predictive of certain plasma markers of inflammation, including interleukin-6 and C-reactive protein. Foods with high inflammatory potential included processed meats, refined grains, and tomatoes; products with low inflammatory potential included beer, wine, green and dark yellow vegetables, and pizza.
Over 25 years' follow-up, 2700 participants developed colorectal cancer. Men in the lowest quintile of proinflammatory diet score had an incidence of 113 per 100,000 person-years, versus 151 per 100,000 in the highest quintile. Among women, incidences were 80 versus 92 per 100,000, respectively. After multivariable adjustment, colorectal cancer risk was significantly higher in men and women in the highest quintiles.
https://jamanetwork.com/journals/jamaoncology/article-abstract/2669777?redirect=true
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MMWR Morb Mortal Wkly Rep 2018 Feb 16; 67:180
2017–18 Seasonal Influenza Vaccine Effectiveness: Interim Data
Vaccine effectiveness was 36% overall and 59% in children under 8 years of age.
The influenza vaccine's poor performance in the Southern Hemisphere led to concerns for low efficacy in the U.S. The CDC calculated the vaccine's effectiveness as of February 3 against medically attended respiratory illnesses. The estimates are based on 4562 adults and children from five study sites enrolled in the Vaccine Effectiveness Network, 38% of whom tested positive for influenza virus.
The findings include:
- Vaccination rates among the sites ranged from 45%–59%, and only 44% of children (<18 years of age) in the study group were vaccinated, compared with 76% of those >64 years of age.
- Influenza A predominated (81% vs. 19% influenza B), with the majority being the H3N2 subtype (85%).
- Overall, vaccine effectiveness against medically attended influenza A and B
was 36%: - 25% against influenza A (H3N2)
- 67% against influenza A (H1N1)
- 42% against influenza B
- Its effectiveness for children 6 months to 8 years of age was higher (59%) than for adults 18–49 years (33%)
COMMENT: It is encouraging that this season's influenza vaccine appears to be performing better than originally expected and better in children than adults. Although it is not a perfect vaccine (no vaccine is perfect), the current influenza vaccine is the best we have for influenza protection, and providers must continue to communicate to families the importance of vaccination. The vaccination rate of 44% in children in this small sample is too low and indicates that most children may be left unprotected from this potentially deadly virus.
CITATION(S): Flannery B et al. Interim estimates of 2017–18 seasonal influenza vaccine effectiveness—United States, February 2018. MMWR Morb Mortal Wkly Rep 2018 Feb 16; 67:180.
(https://doi.org/10.15585/mmwr.mm6706a2)
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Ann Intern Med 2018 Feb 27
Nonpharmacologic Treatment of Chronic Pain in Disadvantaged Patients
Just as in other populations, educational and cognitive-behavioral approaches to chronic pain in poor and minority populations are somewhat effective.
Chronic pain affects more than a third of the U.S. population, accounts for a fifth of all physician visits, and is linked to the current opioid prescription crisis. It disproportionately affects the elderly, minorities, and those with socioeconomic disadvantages. Although poorly responsive to most biomedical approaches, chronic pain does respond to educational, behavioral, and cognitive strategies. However, these strategies have not been well tested in, or adapted to, the most vulnerable populations. Researchers have now conducted a randomized, controlled study of cognitive-behavioral therapy (CBT) or pain education added to usual care or usual care alone in 290 patients with chronic noncancer pain (mean age, 51; below poverty line, 72%; on or applying for disability, 83%).
Both therapies were adapted for 5th-grade literacy and delivered in 10 weekly, 90-minute, group sessions. Usual care provided various treatments (e.g., medication, physical therapy, chiropractic); usual care alone also involved phone contact with study coordinators. Both interventions improved pain on a patient-rated inventory more than usual care alone, without any differences in depressive symptoms. Greater than 30% improvement occurred in 30%, 20%, and 12% of CBT, education, and usual-care groups at posttreatment and 22%, 16%, and 8% of the groups at 6-month follow-up.
COMMENT: Despite data on the usefulness of nonpharmacologic approaches, chronic pain today is largely managed by prescription of potentially harmful and not overly helpful medications. Insurers, for unclear reasons, continue to provide better coverage for medications than for effective psychosocial interventions. In this study, it is unclear whether the usual care arm adequately controlled for the social support provided in the group format of both therapy arms. The modest levels of effectiveness highlight the disorder's chronicity and severity.
CITATION(S): Thorn BE et al. Literacy-adapted cognitive behavioral therapy versus education for chronic pain at low-income clinics: A randomized controlled trial. Ann Intern Med 2018 Feb 27; [e-pub].
(https://doi.org/10.7326/M17-0972)
Kerns RD. Shining the LAMP on efforts to transform pain care in America. Ann Intern Med 2018 Feb 27; [e-pub].
(https://doi.org/10.7326/M18-0061)
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JAMA 2017 Dec 26; 318:2466
Supplemental Calcium or Vitamin D Doesn't Lower Fracture Risk in
Community-Dwelling Adults
Guidelines that recommend supplementation for older adults living in institutions should not be applied to adults living independently.
Several guidelines recommend calcium, vitamin D, or both types of supplementation to prevent fractures in older adults (focusing mostly on frail elders and those living in institutions; Osteoporos Int 2010; 21:1151). In this meta-analysis, researchers identified 33 randomized controlled trials that involved community-dwelling adults (age, ≥50; total patients, 51,145). The trials comprised 44 separate studies (14 of calcium supplementation alone, 17 of vitamin D supplementation alone, and 13 of combined supplementation). Studies that involved patients with corticosteroid-induced osteoporosis, and those in which other drugs or dietary interventions were combined with vitamin D or calcium supplementation were excluded.
The pooled analyses for all three study clusters showed no benefit for any supplementation intervention in reducing relative risk for hip fracture (the primary outcome). Secondary outcomes (vertebral, nonvertebral, and total fractures) also were not affected by any of the interventions. The overall results applied to subgroups with 25-hydroxyvitamin D levels lower than 20 ng/mL or daily dietary calcium intake lower than 900 mg, to women, and to people with previous fractures.
COMMENT: A colleague of mine recently saw a healthy 56-year-old woman who was persistent in her desire for a vitamin D test. When the result came back at 13 ng/mL, she asked about supplementation. Her educational sophistication was such that she was given this meta-analysis and was told that no evidence supported supplementation but that the decision was hers. What she decided is not yet known.
These results clearly show that recommendations for calcium, vitamin D, or combined supplementation in frail older adults or those living in institutions should not be applied to community-living adults. The difference in outcomes with supplementation between these groups might be explained by higher fracture risk in frail or institutionalized elders.
CITATION(S): Zhao J-G et al. Association between calcium or vitamin d supplementation and fracture incidence in community-dwelling older adults: A systematic review and meta-analysis. JAMA 2017 Dec 26; 318:2466.
(http://dx.doi.org/10.1001/jama.2017.19344)
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BMJ 2018 Jan 31; 360:k96
Migraine Is Associated with Excess Stroke and Venous
Thromboembolism Risk
In a cohort study, several other adverse cardiovascular outcomes also were more common.
Prior research has suggested an association between migraine and myocardial infarction and stroke (NEJM JW Gen Med Sep 15 2006 and JAMA 2006; 296:283; NEJM JW Gen Med Jun 1 2007 and JAMA Intern Med2007; 167:795; NEJM JW Gen Med Oct 15 2010 and BMJ 2010; 341:3659). In this nationwide study, researchers in Denmark determined risks for adverse cardiovascular outcomes among 51,000 patients with migraine (but without known cardiovascular disease) who were compared with age- and sex-matched controls from the general population.
Median age at diagnosis of migraine was 35, and 71% of patients were women. After as long as 19 years of follow-up, migraine was associated with significantly higher relative risks for ischemic stroke (hazard ratio, 2.26), hemorrhagic stroke (HR, 1.94), venous thromboembolism (HR, 1.59), myocardial infarction (HR, 1.49), and atrial fibrillation or flutter (HR, 1.25); peripheral artery disease and heart failure occurred at similar rates in both groups. However, absolute risks for these outcomes were low: For example, cumulative incidence of myocardial infarction per 1000 people was 25 for migraine patients and 17 for the general population. The associations were stronger in patients with aura than in patients without aura and stronger in women than in men.
COMMENT: In this study, migraine was associated with excess risk for adverse cardiovascular outcomes. However, given the young age of the study population, absolute risks were low. Whether treatment that reduces migraine frequency and more aggressive cardiovascular prevention strategies in patients with migraine (e.g., lower threshold for prescribing aspirin) mitigate cardiovascular risk is unknown.
CITATION(S): Adelborg K et al. Migraine and risk of cardiovascular diseases: Danish population based matched cohort study. BMJ 2018 Jan 31; 360:k96. (https://doi.org/10.1136/bmj.k96)
Kurth T et al. Migraine and risk of cardiovascular disease: Action to reduce risk is long overdue. BMJ 2018 Jan 31; 360:k275.
(https://doi.org/10.1136/bmj.k275)
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JAMA Intern Med 2018 Feb 12
Risks and Benefits of Supplemental Breast MRI vs. Screening Mammography
MRI screening resulted in more breast biopsies and lower cancer yield than mammography regardless of breast cancer history.
Guidelines recommend supplemental breast MRI in addition to screening mammography for women with >20% excess lifetime risk for breast cancer. However, for women with personal histories of breast cancer (PHBC), only annual mammography is recommended, and evidence is sparse regarding appropriate use of MRI for breast cancer surveillance; still, many breast cancer survivors undergo this imaging. Investigators performed an observational study of >2 million imaging episodes using data from six Breast Cancer Surveillance Consortium registries to evaluate biopsy intensity (fine-needle aspiration, core needle, or surgical excision) and pathology yield (benign, high-risk benign, ductal carcinoma in situ [DCIS], or invasive) after screening mammography versus MRI in women with and without PHBC.
Biopsy rates were more than twofold higher within 90 days following screening breast MRI compared with mammography for women with PHBC and more than fivefold higher in women without PHBC. Compared with breast MRI, mammography-associated biopsy episodes had higher yield of DCIS or invasive cancer (35% vs. 20% for both outcomes) in women with PHBC. More high-risk benign lesions were detected with breast MRI than with mammography regardless of PHBC. Across all risk groups in the database, biopsy rates were fivefold higher for MRI than mammography.
COMMENT: These findings are concordant with recommendations that women should not undergo routine breast MRI for cancer surveillance unless they meet certain criteria (strong family history of breast cancer, oncogenic hereditary mutation, extremely dense breasts, and high-risk lesions such as lobular carcinoma in situ). Women should be made aware of their likelihood of undergoing “second-look” ultrasound and biopsies (with the possibility of benign results) following breast MRI. For women with PHBC, I consider screening MRI if the prior breast cancer was mammographically occult.
CITATION(S): Buist DSM et al. Breast biopsy intensity and findings following breast cancer screening in women with and without a personal history of breast cancer. JAMA Intern Med 2018 Feb 12; [e-pub].
(https://doi.org/10.1001/jamainternmed.2017.8549)
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Osteoporos Int 2017 Dec 27
What Explains the Recent Plateau in Hip Fracture Incidence Among U.S. Women?
Limited reimbursement for bone density assessment along with fears about medications that prevent fractures may be to blame.
Incidence of hip fractures declined steadily among U.S. women from 1995 to 2005 — but has this trend been sustained? Investigators used Medicare data to assess rates of hip fracture from 2002 through 2015 in >2 million women.
In analysis standardized to the 2014 age distribution, incidence of hip fractures declined linearly from 2002 through 2012, then leveled off from 2012 to 2015. Among women aged 65 to74, hip fracture rates rose after 2012.
COMMENT: As the authors note, the earlier decline in hip fracture incidence in the U.S. probably reflects higher frequency of bone mineral density testing, greater awareness of the importance of adequate calcium and vitamin D intake, and increasing use of medications (particularly bisphosphonates) that reduce fracture risk. Recent decreases in Medicare reimbursement for dual-energy x-ray absorptiometry (DXA) have led to fewer such tests being performed. Likewise, fears about the safety of both menopausal hormone therapy and bisphosphonates have led to declines in use of medications that prevent fractures. Considering these trends in aggregate, a “perfect storm” has emerged, resulting in fewer eligible women receiving diagnoses of and treatment for osteoporosis. By keeping detection and management of osteoporosis on our radar screens, we can encourage our average-risk patients to undergo DXA beginning at age 65 (earlier in higher-risk women), while also prescribing fracture-preventive medication when appropriate.
CITATION(S): Lewiecki EM et al. Hip fracture trends in the United States, 2002 to 2015. Osteoporos Int 2017 Dec 27; [e-pub].
(http://dx.doi.org/10.1007/s00198-017-4345-0)
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Obstet Gynecol 2018 Mar; 131:441
Making Good Use of Antihypertensive Medications for Preeclampsia
Administration of common antihypertensives has increased in recent years, with a concomitant decrease in maternal stroke risk.
Maternal hypertensive disorders of pregnancy contribute greatly to the risks for maternal mortality, severe maternal morbidity, and, specifically, stroke. Risk for intracranial hemorrhage can be lowered by timely treatment of severe hypertension, yet we know relatively little about hospital and provider performance regarding this practice. Investigators reviewed hospital discharge and medication records for >239,000 women with preeclampsia to determine patterns of medication use between 2006 and 2015.
The proportions of women with severe and superimposed preeclampsia relative to mild preeclampsia increased throughout the study period. Antihypertensive medication use rose from 38% to 49%, with oral labetalol, intravenous labetalol, hydralazine, and nifedipine the most common choices. Hospital rates of medication administration varied markedly among women with severe preeclampsia. Risk for stroke among women with preeclampsia fell from 6.6 to 3.5 cases per 10,000 deliveries.
COMMENT: Guidance from the American College of Obstetricians and Gynecologists recommends antihypertensive treatment for severe hypertension during pregnancy and postpartum, but this standard is not being universally met. These results are encouraging in showing that likelihood of treatment is on the rise, but unfortunately do not allow for individual-level data to determine the appropriateness of treatment based on blood pressure. Stakeholders such as insurers, regulatory agencies, and state quality care collaboratives should be clear in their expectations for timely initiation of antihypertensive therapy and should direct resources toward incentivizing and measuring equitable adherence to these potentially life-saving interventions.
CITATION(S): Cleary KL et al. Use of antihypertensive medications during delivery hospitalizations complicated by preeclampsia. Obstet Gynecol 2018 Mar; 131:441. (https://doi.org/10.1097/AOG.0000000000002479)
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Lancet Haematol 2018 Jan; 5:e25
Compression Stockings to Prevent Post-Thrombotic Syndrome
In a randomized trial, individualized duration of treatment was as effective as standard-duration treatment.
The history of clinical research on compression stockings to prevent post-thrombotic syndrome after deep venous thrombosis (DVT) is convoluted. Although several small studies initially suggested benefit, the larger SOX trial, in 2013, was negative (NEJM JW Gen Med Jan 15 2014 and Lancet 2014; 383:880). Then, in 2016, the OCTAVIA study showed that 2 years of compression was more effective than 1 year (NEJM JW Gen Med Jul 15 2016 and BMJ 2016; 353:i2691). Poorer adherence to treatment in the SOX trial was one possible reason for its negative result. Now, we have the latest contribution in this sequence.
Researchers provided custom-fitted, knee-high compression stockings (ankle pressure, 30–40 mm Hg) for 865 patients with proximal DVT. After using the stockings for 6 months, patients were randomized into two groups. The standard-treatment group continued to use compression stockings for another 2 years. Individualized-treatment patients were evaluated periodically during 2 years of follow-up and were instructed to stop using compression stockings if persistently favorable scores were noted on a standardized assessment tool for post-thrombotic signs and symptoms. In the individualized group, 55% of patients discontinued stocking use after 6 months, and another 11% stopped after 12 months.
The incidence of post-thrombotic syndrome was nearly identical in the two groups (28% and 29%); most cases developed during the first 6 months of follow-up. Severity of post-thrombotic syndrome also was similar in the two groups.
COMMENT: In this trial — which did not include an untreated control group — individualized duration of compression-stocking use was as effective as 2.5 years of persistent use after acute DVT. If one chooses to use compression stockings in this setting, these findings suggest that treatment can be limited to 1 year in selected patients.
CITATION(S): ten Hate-Coek AJ et al. Individualized versus standard duration of elastic compression therapy for prevention of post-thrombotic syndrome (IDEAL DVT): A multicenter, randomized, single-blind, allocation-concealed, non-inferiority trial. Lancet Haematol 2018 Jan; 5:e25.
(http://dx.doi.org/10.1016/S2352-3026(17)30227-2)
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N Engl J Med 2018 Jan 25; 378:321
Does Solanezumab Slow Cognitive Decline in Alzheimer Disease?
Contrary to prior findings, solanezumab did not significantly slow decline in patients with mild disease.
Evidence suggests that the accumulation of amyloid-beta (Aβ) peptides in the brain is an important factor in the pathophysiology of Alzheimer disease (AD). Genetic, neuropathological, and cell-biological evidence suggest that targeting Aβ could be beneficial in patients with AD. In fact, a secondary analysis of two previous trials (EXPEDITION and EXPEDITION2; Alzheimers Dement 2016; 12:110) showed that solanezumab, a humanized monoclonal antibody designed to bind to and clear soluble Aβ from the brain, significantly slowed cognitive and functional decline in patients with mild AD.
To try to replicate this finding, investigators conducted an industry-funded, randomized, double-blind, placebo-controlled, phase III trial (EXPEDITION3), in which 2129 patients with mild AD received intravenous solanezumab (400 mg weekly for 76 weeks) or placebo. The primary outcome was the change from baseline to week 80 in scores on the 14-item cognitive subscale of the Alzheimer's Disease Assessment Scale (ADAS); scores on this scale range from 0 to 90, with higher scores indicating greater cognitive impairment. The researchers also measured the change in scores on the Mini–Mental State Examination (MMSE); scores on this test range from 0 to 30, with higher scores indicating better cognition.
The mean change in ADAS scores was not significant with solanezumab versus placebo (6.65 and 7.44, respectively). The mean change in MMSE scores was –3.17 with solanezumab and –3.66 with placebo (significance was not measured).
COMMENT: Contrary to results from the prior EXPEDITION studies, solanezumab did not significantly affect cognitive decline in patients with mild AD. So far, attempts at therapeutically targeting Aβ have not been successful, raising doubt on the validity of the amyloid hypothesis.
CITATION(S): Honig LS et al. Trial of solanezumab for mild dementia due to Alzheimer's disease. N Engl J Med 2018 Jan 25; 378:321.
(https://doi.org/10.1056/NEJMoa1705971)
Murphy MP. Amyloid-beta solubility in the treatment of Alzheimer's disease. N Engl J Med 2018 Jan 25; 378:391.
(https://doi.org/10.1056/NEJMe1714638)
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