Benzodiazepines Increase Mortality in Persons with Alzheimer’s Disease

Benzodiazepines Increase Mortality in Persons with Alzheimer’s Disease

Summary: Researchers report an elevated risk of death in Alzheimer’s patients who use benzodiazapines.

Source: University of Eastern Finland.

Benzodiazepine and related drug use is associated with a 40 per cent increase in mortality among persons with Alzheimer’s disease, according to a new study from the University of Eastern Finland. The findings were published in the International Journal of Geriatric Psychiatry.

The study found that the risk of death was increased right from the initiation of benzodiazepine and related drug use. The increased risk of death may result from the adverse events of these drugs, including fall-related injuries, such as hip fractures, as well as pneumonia and stroke.

The study was based on the register-based MEDALZ (Medication Use and Alzheimer’s Disease) cohort, which includes all persons diagnosed with Alzheimer’s disease in Finland during 2005-2011. Persons who had used benzodiazepines and related drugs previously were excluded from this study, and therefore, the study population consisted of 10,380 new users of these drugs. They were compared with 20,760 persons who did not use these drugs.

Although several treatment guidelines state that non-pharmacological options are the first-line treatment of anxiety, agitation and insomnia in persons with dementia, benzodiazepines and related drugs are frequently used in the treatment of these symptoms. If benzodiazepine and related drug use is necessary, these drugs are recommended for short-term use only. These new results encourage more consideration for benzodiazepine and related drug use in persons with dementia.

Image shows how alzheimer's affects the brain.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

Source: Laura Saarelainen – University of Eastern Finland
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is credited to Singer et al., JNeurosci (2017).
Original Research: Abstract for “Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study” by Laura Saarelainen, Anna-Maija Tolppanen, Marjaana Koponen, Antti Tanskanen, Jari Tiihonen, Sirpa Hartikainen, and Heidi Taipale in International Journal of Geriatric Psychiatry. Published online November 15 2017 doi:10.1002/gps.4821

University of Eastern Finland “Benzodiazepines Increase Mortality in Persons with Alzheimer’s Disease.” NeuroscienceNews. NeuroscienceNews, 20 November 2017.
<http://neurosciencenews.com/benzidoazepine-alzheimers-7990/&gt;.

Abstract

Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study

Objective

To investigate the risk of death associated with new benzodiazepine and related drug (BZDR) use in a nationwide cohort of persons with Alzheimer disease (AD).

Methods

The register-based MEDALZ cohort, including all community-dwelling Finns diagnosed with AD during 2005 to 2011 (n = 70 718), was used. Clinically verified AD diagnoses were obtained from the Special Reimbursement Register. Drug use periods were modeled from BZDR purchases, derived from the Prescription Register. To study new users, persons who had any BZDR use during the year preceding the AD diagnosis were excluded.

For each person initiating BZDR use (n = 10 380), 2 nonusers (n = 20 760) were matched on age, gender, and time since AD diagnosis. The outcome was 180-day mortality, and BZDR use was compared with nonuse with Cox regression. Multivariable analyses were adjusted for Charlson comorbidity index, socioeconomic position, hip fractures, psychiatric disorders, substance abuse, stroke, and other psychotropic drug use.

Results

During the follow-up, 5 excess deaths per 100 person-years occurred during BZDR use in comparison to nonuse, and mortality rates were 13.4 (95% confidence interval [CI], 12.2-14.5) and 8.5 (95% CI, 7.9-9.1), respectively. Benzodiazepine and related drug use was associated with an increased risk of death (adjusted hazard ratio = 1.4 [95% CI, 1.2-1.6]), and the association was significant from the initiation of use. Benzodiazepine use was associated with an increased risk of death, whereas benzodiazepine-related drug use was not.

Conclusions

Benzodiazepine and related drug use was associated with an increased risk of death in persons with AD. Our results support treatment guidelines stating that nonpharmacological approaches should be the first-line option for symptomatic treatment of AD.

“Risk of death associated with new benzodiazepine use among persons with Alzheimer disease: A matched cohort study” by Laura Saarelainen, Anna-Maija Tolppanen, Marjaana Koponen, Antti Tanskanen, Jari Tiihonen, Sirpa Hartikainen, and Heidi Taipale in International Journal of Geriatric Psychiatry. Published online November 15 2017 doi:10.1002/gps.4821

Simple EKG Can Determine Whether Patient Has Depression or Bipolar Disorder

Simple EKG Can Determine Whether Patient Has Depression or Bipolar Disorder

Summary: Heart rate variability can indicate whether a person has bipolar disorder or major depression, a new study reports.

Source: Loyola University Health System.

A groundbreaking Loyola Medicine study suggests that a simple 15-minute electrocardiogram could help a physician determine whether a patient has major depression or bipolar disorder.

Bipolar disorder often is misdiagnosed as major depression. But while the symptoms of the depressive phase of bipolar disorder are similar to that of major depression, the treatments are different and often challenging for the physician.

In bipolar disorder, formerly called manic depression, a patient swings between an emotional high (manic episode) and severe depression. Treatment for the depressed phase includes an antidepressant along with a safeguard such as a mood stabilizer or antipsychotic drug to prevent a switch to a manic episode. A physician who misdiagnoses bipolar disorder as major depression could inadvertently trigger a manic episode by prescribing an antidepressant without a safeguard mood stabilizing drug.

The study found that heart rate variability, as measured by an electrocardiogram, indicated whether subjects had major depression or bipolar disorder. (Heart rate variability is a variation in the time interval between heartbeats.) The study, by senior author Angelos Halaris, MD, PhD and colleagues, was published in the World Journal of Biological Psychiatry.

“Having a noninvasive, easy-to-use and affordable test to differentiate between major depression and bipolar disorder would be a major breakthrough in both psychiatric and primary care practices,” Dr. Halaris said. Dr. Halaris said further research is needed to confirm the study’s findings and determine their clinical significance.

Dr. Halaris is a professor in Loyola’s department of psychiatry and behavioral neurosciences and medical director of adult psychiatry.

Major depression is among the most common and severe health problems in the world. In the United States, at least 8 to 10 percent of the population suffers from major depression at any given time. While less common than major depression, bipolar disorder is a significant mental health problem, affecting an estimated 50 million people worldwide.

The Loyola study enrolled 64 adults with major depression and 37 adults with bipolar disorder. All subjects underwent electrocardiograms at the start of the study. Each participant rested comfortably on an exam table while a three-lead electrocardiogram was attached to the chest. After the patient rested for 15 minutes, the electrocardiographic data were collected for 15 minutes.

Using a special software package, researchers converted the electrocardiographic data into the components of heart rate variability. These data were further corrected with specialized software programs developed by study co-author Stephen W. Porges, PhD, of Indiana University’s Kinsey Institute.

In measuring heart rate variability, researchers computed what is known to cardiologists as respiratory sinus arrhythmia (RSA). At the baseline (beginning of the study), the subjects with major depression had significantly higher RSA than those with bipolar disorder.

In a secondary finding, researchers found that patients with bipolar disorder had higher blood levels of inflammation biomarkers than patients with major depression. Inflammation occurs when the immune system revs up in response to a stressful condition such as bipolar disorder.

ABOUT THIS NEUROSCIENCE RESEARCH ARTICLE

The study is titled “Low cardiac vagal tone index by heart rate variability differentiates bipolar from major depression.” In addition to Drs. Halaris and Porges, other co-authors are Brandon Hage, MD, a graduate of Loyola University Chicago Stritch School of Medicine now at the University of Pittsburgh (first author); Stritch student Briana Britton; Loyola psychiatric resident David Daniels, MD; and Keri Heilman, PhD of the University of North Carolina.

Source: Jim Ritter – Loyola University Health System
Publisher: Organized by NeuroscienceNews.com.
Image Source: NeuroscienceNews.com image is in the public domain.
Original Research: Abstract for “Distinguishing bipolar II depression from unipolar major depressive disorder: Differences in heart rate variability” by Hsin-An Chang Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Chuan-Chia Chang, Terry B. J. Kuo & San-Yuan Huang in World Journal of Biological Psychiatry. Published online November 14 2017 doi:10.3109/15622975.2015.1017606

Loyola University Health System “Simple EKG Can Determine Whether Patient Has Depression or Bipolar Disorder.” NeuroscienceNews. NeuroscienceNews, 20 November 2017.
<http://neurosciencenews.com/ekg-depression-bipolar-7991/&gt;.

Abstract

Distinguishing bipolar II depression from unipolar major depressive disorder: Differences in heart rate variability

Objectives. Bipolar II (BPII) depression is commonly misdiagnosed as unipolar depression (UD); however, an objective and reliable tool to differentiate between these disorders is lacking. Whether cardiac autonomic function can be used as a biomarker to distinguish BPII from UD is unknown.

Methods. We recruited 116 and 591 physically healthy patients with BPII depression and UD, respectively, and 421 healthy volunteers aged 20–65 years. Interviewer and self-reported measures of depression/anxiety severity were obtained. Cardiac autonomic function was evaluated by heart rate variability (HRV) and frequency-domain indices of HRV.

Results. Patients with BPII depression exhibited significantly lower mean R–R intervals, variance (total HRV), low frequency (LF)-HRV, and high frequency (HF)-HRV but higher LF/HF ratio compared to those with UD. The significant differences remained after adjusting for age. Compared to the controls, the patients with BPII depression showed cardiac sympathetic excitation with reciprocal vagal impairment, whereas the UD patients showed only vagal impairment. Depression severity independently contributed to decreased HRV and vagal tone in both the patients with BPII depression and UD, but increased sympathetic tone only in those with BPII depression.

Conclusions. HRV may aid in the differential diagnosis of BPII depression and UD as an adjunct to diagnostic interviews.

“Distinguishing bipolar II depression from unipolar major depressive disorder: Differences in heart rate variability” by Hsin-An Chang Department of Psychiatry, Tri-Service General Hospital, National Defense Medical Center, Taipei, Taiwan, Chuan-Chia Chang, Terry B. J. Kuo & San-Yuan Huang in World Journal of Biological Psychiatry. Published online November 14 2017 doi:10.3109/15622975.2015.1017606

Reduce stress to slow aging and Alzheimer’s – Dementia

Of the 100 year old who died and their brain were later on examined to have Alzheimer’s, 25% of them has but did not exhibit signs of Alzheimer’s.

Why?

They are not stressed, they get massage, take a walk and are surrounded by family and support of the community.

I train my caregivers to comfort our seniors with massage, music, walk in the sun, and happy conversations with loving spirit.

Connie


 

Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo

Emerging studies suggest a role for tau in regulating the biology of RNA binding proteins (RBPs). We now show that reducing the RBP T-cell intracellular antigen 1 (TIA1) in vivo protects against neurodegeneration and prolongs survival in transgenic P301S Tau mice. Biochemical fractionation shows co-enrichment and co-localization of tau oligomers and RBPs in transgenic P301S Tau mice. Reducing TIA1 decreased the number and size of granules co-localizing with stress granule markers. Decreasing TIA1 also inhibited the accumulation of tau oligomers at the expense of increasing neurofibrillary tangles. Despite the increase in neurofibrillary tangles, TIA1 reduction increased neuronal survival and rescued behavioral deficits and lifespan. These data provide in vivo evidence that TIA1 plays a key role in mediating toxicity and further suggest that RBPs direct the pathway of tau aggregation and the resulting neurodegeneration. We propose a model in which dysfunction of the translational stress response leads to tau-mediated pathology.

“Reducing the RNA binding protein TIA1 protects against tau-mediated neurodegeneration in vivo” by Daniel J. Apicco, Peter E. A. Ash, Brandon Maziuk, Chelsey LeBlang, Maria Medalla, Ali Al Abdullatif, Antonio Ferragud, Emily Botelho, Heather I. Ballance, Uma Dhawan, Samantha Boudeau, Anna Lourdes Cruz, Daniel Kashy, Aria Wong, Lisa R. Goldberg, Neema Yazdani, Cheng Zhang, Choong Y. Ung, Yorghos Tripodis, Nicholas M. Kanaan, Tsuneya Ikezu, Pietro Cottone, John Leszyk, Hu Li, Jennifer Luebke, Camron D. Bryant & Benjamin Wolozin in Nature Neuroscience. Published online November 20 2017 doi:10.1038/s41593-017-0022-z


 

TIA1 is a 3’UTR mRNA binding protein that can bind the 5’TOP sequence of 5’TOP mRNAs. It is associated with programmed cell death (apoptosis) and regulates alternative splicing of the gene encoding the Fas receptor, an apoptosis-promoting protein.[1] Under stress conditions, TIA1 localizes to cellular RNA-protein conglomerations called stress granules.[2]

Mutations in the TIA1 gene have been associated with amyotrophic lateral sclerosisfrontotemporal dementia, and Welander distal myopathy.[3][4][5]

Sunshine and mental health

SUNSHINE

Calm worries and increase cognitive flexibility with exercise and nutrition

By Dr Amen

The Anterior Cingulate Gyrus (ACG)  affects you when it works too hard and you are over 50 years old with chronic stress and poor nutrition. Nutrition, sunshine, volunteering, whole foods, massage, caregivers and physical exercise can help calm worries and cognitive flexibility. It increases your energy and can distract you from thoughts that loop around your mind.

Nutrition

An overactive ACG can be calmed down with certain foods that increase serotonin levels. Search this site: serotonin, dopamine, Parkinsons, Alzheimer, whole foods, inflammation, detox

  • Sweet potatoes and garbanzo beans (complex carbs)
  • Foods rich in L-tryptophan such as chicken, turkey, wild salmon, beeft, nut butter, eggs and green peas

Supplements

  • 5HTP
  • Inositol
  • Saffron
  • Vitamin B complex: B6 and others
  • L-tryptophan
  • St John’s Wort
  • Omega 3x higher in DHA
  • Anti-oxidants

Email Connie at motherhealth@gmail.com as your personal health coach.

http://clubalthea.pxproducts.com/products-2

NANO CARROT

 

Genetic Factors in Depression

Genetic factors involved in depression have been difficult to identify. In 2003 Science published an influential[1] study of Avshalom Caspi et al. who found that a gene-environment interaction (GxE) may explain why life stress is a predictor for depressive episodes in some individuals, but not in others, depending on an allelic variation of the serotonin-transporter-linked promoter region (5-HTTLPR).[2] Soon after, the results were replicated by Kenneth Kendler‘s group, raising hopes in the psychiatric genetics community.[3] By 2007 there were 11 replications, 3 partial replication and 3 non-replications of this proposed GxE. However, two of the largest studies[4][5]were negative.[6] Two 2009 meta-analyses were also negative; one included 14 studies,[7] and the other five, owing to different study selection criteria.[8]

A 2010 review found 17 replications, 8 partial replications (interaction only in females or only with one of several types of adversity), and 9 non-replications (no interaction or an interaction in the opposite direction). It also found that all studies using objective indicators or structured interviews to assess stress replicated the gene–environment interaction fully or partially, whereas all non-replications relied on self-reported measures of adversity. This review also argued that both 2009 meta-analyses were significantly biased toward negative studies.[9]

BDNF polymorphisms have also been hypothesized to have a genetic influence, but replication results have been mixed and, as of 2005, were insufficient for a meta-analysis.[10] Studies also indicate an association of decreased BDNF production with suicidal behavior.[11] However, findings from gene-environment interactions studies suggest that the current BDNF models of depression are too simplistic.[12]

A 2008 study found interactions (biological epistasis) in the signaling pathways of the BDNF and the serotonin transporter; the BDNF Val66Met allele, which was predicted to have reduced responsitivity to serotonin, was found to exercise protective effects in individuals with the short 5-HTTLPR allele that is otherwise believed to predispose individuals to depressive episodes after stressful events.[13] Thus, the BDNF-mediated signalling involved in neuroplastic responses to stress and antidepressants is influenced by other genetic and environmental modifiers.[12]

The largest genome-wide study to date failed to identify variants with genome-wide significance in over 9000 cases.[14]

Recently, a genetics study positively identified two variants with genome-wide association with major depressive disorder (MDD).[15] This study, conducted in Chinese Han women, identified two variants in intronic regions near SIRT1 and LHPP.[16]

Attempts to find a correlation between norepinephrine transporter polymorphisms and depression have yielded negative results.[17]

One review identified multiple frequently studied candidate genes. The 5-HTT SLC6A4 and 5-HTR2A gene’s yielded inconsistent results, however they may predict treatment results. Mixed results were found for BDNF Val66Met polymorphisms. Polymorphisms in tryptophan hydroxylase genes were found to be associated with suicidal behavior.[18]

A meta analysis of 182 case controlled genetic studies published in 2008 found Apolipoprotein verepsilon 2 to be protective, and found GNB3 825T, MTHFR 677T, SLC6A4 44bp insertion or deletions, and SLC6A3 40 bpVNTR 9/10 genotype conferred risk.[


MTHFR 677T

Methylene tetrahydrofolate reductase (MTHFR) is the rate-limiting enzyme in the methyl cycle, and it is encoded by the MTHFR gene.[3] Methylenetetrahydrofolate reductase catalyzes the conversion of 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, a cosubstrate for homocysteine remethylation to methionine. Natural variation in this gene is common in healthy people. Although some variants have been reported to influence susceptibility to occlusive vascular disease, neural tube defects, Alzheimer’s disease and other forms of dementia, colon cancer, and acute leukemia, findings from small early studies have not been reproduced. Some mutations in this gene are associated with methylenetetrahydrofolate reductase deficiency.


 

GNB3 825T GENE

gnas.JPG


LHPP

LHPP (Phospholysine Phosphohistidine Inorganic Pyrophosphate Phosphatase) is a Protein Coding gene. Among its related pathways are Purine metabolism (REACTOME) and Respiratory electron transport, ATP synthesis by chemiosmotic coupling, and heat production by uncoupling proteins.. GO annotations related to this gene include protein homodimerization activity and inorganic diphosphatase activity. An important paralog of this gene is HDHD2.