Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults

Posted on February 3, 2016 by Maurice Preter MD

Association of Seafood Consumption, Brain Mercury Level, and APOE ε4 Status With Brain Neuropathology in Older Adults

Martha Clare Morris, ScD1; John Brockman, PhD2; Julie A. Schneider, MD, MPH3,4,5; Yamin Wang, PhD1; David A. Bennett, MD3,4; Christy C. Tangney, PhD6; Ondine van de Rest, PhD7

 

JAMA. 2016;315(5):489-497. doi:10.1001/jama.2015.19451.

Importance  Seafood consumption is promoted for its many health benefits even though its contamination by mercury, a known neurotoxin, is a growing concern.

Objective  To determine whether seafood consumption is correlated with increased brain mercury levels and also whether seafood consumption or brain mercury levels are correlated with brain neuropathologies.

Design, Setting, and Participants  Cross-sectional analyses of deceased participants in the Memory and Aging Project clinical neuropathological cohort study, 2004-2013. Participants resided in Chicago retirement communities and subsidized housing. The study included 286 autopsied brains of 554 deceased participants (51.6%). The mean (SD) age at death was 89.9 (6.1) years, 67% (193) were women, and the mean (SD) educational attainment was 14.6 (2.7) years.

Exposures  Seafood intake was first measured by a food frequency questionnaire at a mean of 4.5 years before death.

Main Outcomes and Measures  Dementia-related pathologies assessed were Alzheimer disease, Lewy bodies, and the number of macroinfarcts and microinfarcts. Dietary consumption of seafood and n-3 fatty acids was annually assessed by a food frequency questionnaire in the years before death. Tissue concentrations of mercury and selenium were measured using instrumental neutron activation analyses.

Results  Among the 286 autopsied brains of 544 participants, brain mercury levels were positively correlated with the number of seafood meals consumed per week (ρ = 0.16; P = .02). In models adjusted for age, sex, education, and total energy intake, seafood consumption (≥ 1 meal[s]/week) was significantly correlated with less Alzheimer disease pathology including lower density of neuritic plaques (β = −0.69 score units [95% CI, −1.34 to −0.04]), less severe and widespread neurofibrillary tangles (β = −0.77 score units [95% CI, −1.52 to −0.02]), and lower neuropathologically defined Alzheimer disease (β = −0.53 score units [95% CI, −0.96 to −0.10]) but only among apolipoprotein E (APOE ε4) carriers. Higher intake levels of α-linolenic acid (18:3 n-3) were correlated with lower odds of cerebral macroinfarctions (odds ratio for tertiles 3 vs 1, 0.51 [95% CI, 0.27 to 0.94]). Fish oil supplementation had no statistically significant correlation with any neuropathologic marker. Higher brain concentrations of mercury were not significantly correlated with increased levels of brain neuropathology.

Conclusions and Relevance  In cross-sectional analyses, moderate seafood consumption was correlated with lesser Alzheimer disease neuropathology. Although seafood consumption was also correlated with higher brain levels of mercury, these levels were not correlated with brain neuropathology.

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Overprescribing Anticholinergics May Hurt Recovery in Elderly

Posted on February 1, 2016 by Maurice Preter MD

Overprescribing Anticholinergics May Hurt Recovery in Elderly

http://news.psu.edu/story/389729/2016/01/28/research/anticholinergics-may-not-be-best-choice-rehab-patients-dementia

UNIVERSITY PARK, Pa. — During rehabilitation following an acute hospital stay, medications that block neurotransmitters may be overprescribed to older patients suffering from delirium superimposed on dementia, according to health researchers.

Specifically, strong anticholinergic medications may be prescribed to older adults when there are other suitable options. An anticholinergic medication blocks the neurotransmitter acetylcholine in the nervous system. These drugs are prescribed for a variety of symptoms, including incontinence, depression and insomnia. While their use can be very beneficial to some, they are also known to have significant adverse effects.

“In this study, people on anticholinergic medications had worse attention and physical function, and a longer stay (at the rehab facility) by four days, when compared to patients not on these medications,” said Ann Kolanowski, professor of nursing, Penn State.

The researchers observed 99 patients for 30 days, or until they were released, beginning the day they entered rehabilitation. Upon entering the rehab facility, all of the participants had both delirium and dementia, were 65 or older and did not have any other neurological problems.

The participants’ cognition and physical function were assessed daily by research staff. Physical function was measured by noting the amount of time and assistance patients needed to complete a task, such as feeding and dressing themselves and walking. Among other measures, patients’ cognition was measured by being given increasingly longer sequences of numbers to repeat both forwards and backwards until they missed two sequences in a row. Kolanowski and colleagues report their findings in a recent issue of the American Journal of Geriatric Psychiatry.

Anticholinergic drugs are ranked in the study according to their effect on cognition as mild, moderate and severe. A quarter of the patients were taking a medication with a moderate or severe anticholinergic effect, while 15 percent of the patients were not taking any anticholinergic medications. The remaining patients were taking a medication with mild anticholinergic effects.

The researchers found that patients who had been taking a medication with moderate or severe anticholinergic effects performed more poorly on a test of attention than they had during the previous week and also had lower physical function than the previous week.

“For people with dementia, the loss of physical function is a major risk factor for permanent institutionalization, and contributes heavily to the national burden of healthcare costs,” said the researchers. “The goal of post-acute care is to optimize function. For people with dementia, appropriate anticholinergic medication management may help achieve rehabilitation goals and reduce the cost of care.”

Jacqueline Mogle, assistant professor, Donna M. Fick, Distinguished Professor and director, Hartford Center of Geriatric Nursing Excellence, Nikki Hill, assistant professor, Paula Mulhall, research technologist, Liza Behrens, doctoral student, and Elise Colanecco, doctoral student, all College of Nursing, Penn State; Noll Campbell, research assistant professor, pharmacy, Purdue University; Malaz Boustani, professor, medicine, Indiana University; and Linda Clare, professor, clinical psychology, Washington Singer Laboratories, University of Exeter; all collaborated on this research as well.

The National Institute of Nursing Research at the National Institutes of Health supported this research.

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Can Vitamin D Benefit Patients with Prediabetes?

Posted on February 1, 2016 by Maurice Preter MD

 

Can Vitamin D Benefit Patients with Prediabetes?

No Effect of High-Dose Vitamin D Treatment on β-Cell Function, Insulin Sensitivity, or Glucose Homeostasis in Subjects With Abnormal Glucose Tolerance: A Randomized Clinical Trial

Henrik Wagner1⇑, Michael Alvarsson1, Buster Mannheimer2, Marie Degerblad1 and Claes Göran Östenson1

http://care.diabetesjournals.org/content/early/2016/01/07/dc15
-1057.abstract

Abstract

OBJECTIVE There has been conflicting evidence regarding the potential role of vitamin D in glucose homeostasis. This study was designed to investigate the effect of high-dose vitamin D3 treatment on β-cell function, insulin sensitivity, and glucose tolerance in subjects with prediabetes or diet-treated type 2 diabetes.

RESEARCH DESIGN AND METHODS Subjects (n = 44) were randomized to 30,000 IU vitamin D3 once weekly or placebo for 8 weeks. Hyperglycemic clamp assessed first-phase (0–12 min) and second-phase (12–120 min) insulin response, insulin sensitivity, and disposition index (DI). An oral glucose tolerance test assessed glucose tolerance and glycosylated hemoglobin assessed glycemic control.

RESULTS A total of 21 (vitamin D) and 22 (placebo) subjects completed the study, respectively. Season-adjusted 25-OH-vitamin D [25(OH)D] levels were doubled in the active treated group (43–82 nmol/L). No effect of vitamin D treatment, compared with placebo, was seen on first-phase or second-phase insulin secretion. There were no group differences in insulin sensitivity, DI, or any measures of glycemic control. No hypercalcemia or other adverse effects of vitamin D treatment were seen compared with placebo. Subgroup analyses of those with the lowest basal and greatest increase in 25(OH)D levels did not change these results.

CONCLUSIONS This study gives no support for any substantial effect of high-dose vitamin D treatment for 8 weeks in prediabetes or diet-treated type 2 diabetes on β-cell function, insulin sensitivity, or glycemic control.

  • Received May 19, 2015.
  • Accepted December 4, 2015.
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True Risk of Serious Harms with Antidepressants Still Uncertain

Posted on January 31, 2016 by Maurice Preter MD

True Risk of Serious Harms with Antidepressants Still Uncertain

http://www.bmj.com/content/352/bmj.i65

Abstract

Objective To study serious harms associated with selective serotonin and serotonin-norepinephrine reuptake inhibitors.

Design Systematic review and meta-analysis.

Main outcome measures Mortality and suicidality. Secondary outcomes were aggressive behaviour and akathisia.

Data sources Clinical study reports for duloxetine, fluoxetine, paroxetine, sertraline, and venlafaxine obtained from the European and UK drug regulators, and summary trial reports for duloxetine and fluoxetine from Eli Lilly’s website.

Eligibility criteria for study selection Double blind placebo controlled trials that contained any patient narratives or individual patient listings of harms.

Data extraction and analysis Two researchers extracted data independently; the outcomes were meta-analysed by Peto’s exact method (fixed effect model).

Results We included 70 trials (64 381 pages of clinical study reports) with 18 526 patients. These trials had limitations in the study design and discrepancies in reporting, which may have led to serious under-reporting of harms. For example, some outcomes appeared only in individual patient listings in appendices, which we had for only 32 trials, and we did not have case report forms for any of the trials. Differences in mortality (all deaths were in adults, odds ratio 1.28, 95% confidence interval 0.40 to 4.06), suicidality (1.21, 0.84 to 1.74), and akathisia (2.04, 0.93 to 4.48) were not significant, whereas patients taking antidepressants displayed more aggressive behaviour (1.93, 1.26 to 2.95). For adults, the odds ratios were 0.81 (0.51 to 1.28) for suicidality, 1.09 (0.55 to 2.14) for aggression, and 2.00 (0.79 to 5.04) for akathisia. The corresponding values for children and adolescents were 2.39 (1.31 to 4.33), 2.79 (1.62 to 4.81), and 2.15 (0.48 to 9.65). In the summary trial reports on Eli Lilly’s website, almost all deaths were noted, but all suicidal ideation events were missing, and the information on the remaining outcomes was incomplete.

Conclusions Because of the shortcomings identified and having only partial access to appendices with no access to case report forms, the harms could not be estimated accurately. In adults there was no significant increase in all four outcomes, but in children and adolescents the risk of suicidality and aggression doubled. To elucidate the harms reliably, access to anonymised individual patient data is needed.

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Quetiapine safety in older adults?

Posted on January 31, 2016 by Maurice Preter MD

Quetiapine safety in older adults?

Journal of Clinical Pharmacy and Therapeutics

Volume 41,  Issue 1, pages 7–18, February 2016

http://onlinelibrary.wiley.com/doi/10.1111/jcpt.12357/abstract

Abstract

WHAT IS KNOWN AND OBJECTIVE:

Quetiapine is a second-generation antipsychotic that is commonly prescribed for a range of approved and off-label indications in older adults. However, little is known about its safety in this population. The available evidence on quetiapine safety is based on studies on second-generation antipsychotics as a group, often in the general population and for approved indications. There are no systematicreviews on the safety of quetiapine in older adults, and therefore, there is a need for systematically assessing quetiapine safety in this group of patients to establish an appropriate safety profile for this vulnerable population. The aim of this paper was to review and describe adverse drug events associated with quetiapine use in older adults.

METHODS:

A systematic literature search was performed based on the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines. Databases searched were CINAHL, PubMed, Medline, PsycInfo and the Cochrane Library.

RESULTS AND DISCUSSION:

Sixty-nine papers met the inclusion criteria. The majority of the studies (n = 36, 52%) were observational, and 11 (16%) were randomized controlled trials (RCTs). Most of the reported indications (75%) were off-label. The most commonly reported adverse events were somnolence (25-39%), dizziness (15-27%), headache (10-23%), postural hypotension (6-18%) and weight gain (11-30%). From the included RCTs, comparing quetiapine with placebo, quetiapine resulted in significantly greater cognitive impairment, higher rates of falls and injury and increased mortality in patients with parkinsonism, but not in patients with dementia. Compared with risperidone and olanzapine, quetiapine had significantly lower risk of mortality, reduced rate of cerebrovascular events, increased rate of falls and injury and less metabolic disorders compared with olanzapine, but higher metabolic disorders compared with risperidone.

WHAT IS NEW AND CONCLUSION:

This work provides full characterization of quetiapine safety in older people, which may help healthcare providers better anticipate, prevent and manage ADEs in this population.

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