Archives for March 2016

Relationships between Caloric Expenditure and Gray Matter in Cardiovascular Health Study

J Alzheimers Dis. 2016 Mar 11. [Epub ahead of print]

Longitudinal Relationships between Caloric Expenditure and Gray Matter in the Cardiovascular Health Study.

Raji CA1, Merrill DA2, Eyre H3,4, Mallam S3, Torosyan N3, Erickson KI5, Lopez OL6, Becker JT5,6,7, Carmichael OT8, Gach HM9, Thompson PM10, Longstreth WT11, Kuller LH12.



Physical activity (PA) can be neuroprotective and reduce the risk for Alzheimer’s disease (AD). In assessing physical activity [swimming, hiking, aerobics, jogging, tennis, racquetball, walking, gardening, mowing, raking, golfing, bicycling, dancing, calisthenics, and riding an exercise cycle], caloric expenditure [kilocalories per week] is a proxy marker reflecting the sum total of multiple physical activity types conducted by an individual.


To assess caloric expenditure, as a proxy marker of PA, as a predictive measure of gray matter (GM) volumes in the normal and cognitively impaired elderly persons.


All subjects in this study were recruited from the Institutional Review Board approved Cardiovascular Health Study (CHS), a multisite population-based longitudinal study in persons aged 65 and older.

We analyzed a sub-sample of CHS participants 876 subjects (mean age 78.3, 57.5% F, 42.5% M) who had i) energy output assessed as kilocalories (kcal) per week using the standardized Minnesota Leisure-Time Activities questionnaire, ii) cognitive assessments for clinical classification of normal cognition, mild cognitive impairment (MCI), and AD, and iii) volumetric MR imaging of the brain.

Voxel-based morphometry modeled the relationship between kcal/week and GM volumes while accounting for standard covariates including head size, age, sex, white matter hyperintensity lesions, MCI or AD status, and site. Multiple comparisons were controlled using a False Discovery Rate of 5 percent.


Higher energy output, from a variety of physical activity types, was associated with larger GM volumes in frontal, temporal, and parietal lobes, as well as hippocampus, thalamus, and basal ganglia. High levels of caloric expenditure moderated neurodegeneration-associated volume loss in the precuneus, posterior cingulate, and cerebellar vermis.

Cardiovascular Health Study

Main effect of increasing caloric expenditure on gray matter structure in the Cardiovascular Health Study. Red and yellow colors reflect larger gray matter volumes in the frontal, temporal, and parietal lobes (Above).

Cardiovascular Health Study2

Main effect of change in physical activity over time on gray matter structure. Areas that demonstrated more gray matter volume with increased physical activity over time include the left inferior orbital frontal cortex and left precuneus (Above).


Increasing energy output from a variety of physical activities is related to larger gray matter volumes in the elderly, regardless of cognitive status.


Copyright ©2015 IOS Press All rights reserved.


Keep Moving to Halve the Risk of Alzheimer’s

(MedicalNewsToday) To dramatically reduce your chances of getting Alzheimer’s, grab your gear and get down to the gym, out into the garden or even down to the local dance spot. A new study, published in the Journal of Alzheimer’s Disease, finds that any kind of exercise can improve brain volume and cut the risk of the disease by 50%.

The Alzheimer’s Association estimate that Alzheimer’s disease currently affects 5.1 million Americans. Numbers are expected to rise to 13.8 million over the next 30 years, as the aging population expands.

There is currently no cure, and interventions focus on prevention through lifestyle management.

Dr. Cyrus A. Raji, PhD, of the University of California-Los Angeles (UCLA) Medical Center, and colleagues teamed up with researchers from the University of Pittsburgh in Pennsylvania to find out more about the effect of aerobic exercise on the brain.

They looked at a cohort of 876 patients enrolled in the 30-year Cardiovascular Health Study, across four research sites in the US. The average age of participants was 78 years.

The team examined details of participants’ memory over time and administered standard questionnaires about their physical activity habits, which varied widely and included gardening, dancing and riding an exercise cycle at the gym.

MRI Scans Reflect Benefits of Exercise on the Brain

The investigators also carried out brain scans through magnetic resonance imaging (MRI), and they analyzed them using advanced computer algorithms. This enabled them to measure the volumes of those brain structures, such as the hippocampus, which are associated with memory and Alzheimer’s.

They then correlated the participants’ physical activities to their brain volumes and summarized the weekly caloric output from these activities.

Results showed that the more physical activity an individual did, the larger the brain volumes in key parts of the brain, and specifically the frontal, temporal and parietal lobes, including the hippocampus. Moreover, individuals whose brains benefitted from additional physical activity had a 50% lower risk of Alzheimer’s dementia.

Around 25% of the participants had mild cognitive impairment associated with Alzheimer’s. Increasing their physical activity was also found to boost their brain volumes.

George Perry, PhD, who is the editor-in-chief of the Journal of Alzheimer’s Disease, hopes that the current study will be the first step toward objective biological measurement in the field of Alzheimer’s.

Dr. Raji adds:

“We have no magic bullet cure for Alzheimer’s disease. Our focus needs to be on prevention.”


Longitudinal Relationships between Caloric Expenditure and Gray Matter in the Cardiovascular Health Study Cyrus A. Raji et al., Journal of Alzheimer’s Disease, doi: 10.3233/JAD-160057, published 11 March 2016.

IOS news release, accessed 10 March 2016.

MediLexicon International Ltd, Bexhill-on-Sea, UK

© 2004-2016 All rights reserved.


For Older Adults with Dementia, Transitions in Care Can Increase Risk for Serious Problems

(American Geriatrics Society via ScienceDaily) A transition is a physical move from one location to another with a stay of at least one night. For older adults, especially those with dementia, some transitions may be unavoidable and necessary. However, unnecessary transitions are linked to problems such as medication errors, hospital readmissions, and increased risk of death.

What’s more, good dementia care emphasizes the need for familiar people and familiar environments, and this can be more difficult to support when too many transitions take place. Having coordinated care and a long-term care plan in place that considers the needs of a person with dementia may reduce unnecessary transitions, say the authors of a study published in the Journal of the American Geriatrics Society.

In their study, researchers from the UBC Centre for Health Services and Policy Research in Vancouver, British Columbia, followed 6,876 people aged 65 and older who were diagnosed with dementia between 2001 and 2002. The researchers analyzed healthcare data from 2000 until the study ended in 2011. Besides dementia, 23 percent of the group had no other chronic diseases at the beginning of the study, while 44 percent of the group had two or more chronic diseases.

The researchers found a spike in the number of transitions during the first year of dementia diagnosis. Sixty-five percent of the study participants experienced at least one transition during the year of their diagnosis; 17 percent experienced three or more transitions, most of which were hospitalizations. More than 60 percent of people were hospitalized in the year of their diagnosis, and these hospital stays generally lasted for a month or longer.

In addition to data regarding the year of diagnosis, the researchers also uncovered that people experienced a higher number of transitions the year prior to and the year of their death. Receiving a prescription for an antipsychotic medication or benzodiazepine, as well as living in more rural areas, were linked to a higher number of transitions, too.

The researchers learned that receiving ongoing care from a known primary care physician and receiving care consistent with dementia guidelines were linked to fewer transitions. Depending on each person’s needs, guideline recommendations include:

  • Receiving recommended lab tests
  • Seeing a dementia specialist
  • Having a physical exam
  • Participating in counseling

The researchers concluded that, for people with dementia and their caregivers, the year of diagnosis is often overwhelmingly stressful. Still, steps can be taken to lessen transitions and improve care. These include:

  • Connection to an ongoing primary care provider
  • Early, advanced care planning consistent with one’s wishes
  • Having a patient advocate who can help with care coordination
  • Increasing caregiver and provider awareness of community support systems

Journal Reference

Saskia N. Sivananthan, Kimberlyn M. McGrail. Diagnosis and Disruption: Population-Level Analysis Identifying Points of Care at Which Transitions Are Highest for People with Dementia and Factors That Contribute to Them. Journal of the American Geriatrics Society, 2016; 64 (3): 569 DOI: 10.1111/jgs.14033

Copyright 2015 ScienceDaily or by third parties, where indicated.


Alzheimer’s Disease: Managing Eating, Drinking, and Swallowing Problems

(Alzheimer’s Australia) Meal times provide us with an opportunity to spend time with our family and friends, as well as sharing food together. When caring for someone with dementia meal times can sometimes become stressful. Loss of memory and problems with judgment can cause difficulties in relation to eating and nutrition for many people with dementia. There are many ways to improve the situation.

Loss of Appetite

Forgetting how to chew and swallow, ill-fitting dentures, insufficient physical activity, and being embarrassed by difficulties can all result in a loss of appetite.

What to try

  • Check with the doctor to make sure that there are no treatable causes for loss of appetite, such as acute illness or depression
  • Offer meals at regular times each day
  • Allow the person to eat when hungry
  • Encourage physical exercise
  • Provide balanced meals to avoid constipation
  • Try a glass of juice, wine or sherry, if medications permit, before the meal to whet appetite
  • Offer ice cream or milk shakes
  • Try to prepare familiar foods in familiar ways, especially foods that are favourites
  • Encourage eating all or most of one food before moving on to the next: some people can become confused when the tastes and textures change
  • Try to make mealtimes simple, relaxed and calm. Be sure to allow enough time for a meal. Assisting a very impaired person can take up to an hour
  • Consult a doctor if there is a significant weight loss (such as 2.5kg in 6 weeks)
  • Check with the doctor about vitamin supplements.

Overeating or Insatiable Appetite

What to try

  • Leaving snack foods on the table may be enough to satisfy some people
  • Try 5-6 small meals each day
  • Have low calorie snacks available, such as apples and carrots
  • Consider whether other activities such as walks, or increased social contacts may help
  • Lock some foods in cupboards, if necessary.

Sweet Cravings

What to try

  • Check medications for side effects. Some antidepressant medications can cause a craving for sweets
  • Try milk shakes, egg nogs or low calorie ice cream.

Mouth, Chewing, and Swallowing Problems

Some causes of problems with eating may relate to the mouth. A dry mouth, or mouth discomfort from gum disease or ill-fitting dentures are common problems.

What to try

  • Have a dental check up of gums, teeth and dentures
  • Moisten food with gravies and sauces if a dry mouth is causing problems
  • For chewing problems, try light pressure on the lips or under the chin, tell the person when to chew, demonstrate chewing, moisten foods or offer small bites one at a time
  • For swallowing problems, remind the person to swallow with each bite, stroke the throat gently, check the mouth to see if food has been swallowed, do not give foods which are hard to swallow, offer smaller bites and moisten food
  • Consult the doctor if choking problems develop.

At the Table

Pouring a glass of juice into a bowl of soup, buttering the serviette or eating dessert with a knife indicate that a person with dementia is having difficulty at the dinner table.

What to try

  • Serve one course at a time and remove other distracting items from the table such as extra cutlery glasses or table decorations
  • Ensure that the crockery is plain and is a different colour to the plain table cloth
  • If the use of cutlery is too difficult serve finger food
  • Eat with the person with dementia so that they can copy you
  • Make sure that they are not rushed
  • Keep noise and activities in the environment to a minimum
  • Ensure there is adequate lighting
  • Serve familiar food.

Other Considerations

  • Keep eating simple. Not all food has to be eaten with cutlery if this is becoming difficult. Finger food can be a nutritious and easy alternative
  • Keep in mind a person’s past history with food. They may have always had a small appetite, been a voracious eater or had a sweet tooth Watch food temperatures. While warm food is more appetising, some people with dementia have lost the ability to judge when food is hot or cold. Beware of using Styrofoam cups which not only hold the heat for a long time, but also tip over easily
  • Spoiled food in the refrigerator, hiding food or not eating regularly may all be signs that someone living alone is in need of more support
  • Many people with dementia do not get enough fluids because they may forget to drink or may no longer recognise the sensation of thirst. Be sure to offer regular drinks of water, juice or other fluids to avoid dehydration
  • Many eating problems are temporary and will change as the person’s abilities deteriorate.

Adapted from Understanding difficult behaviours, by Anne Robinsons, Beth Spencer and Laurie White.

Alzheimer’s Australia


Four Ways to Deal with Stress Right Now

(American Heart Association) Here are four simple techniques for managing stress:

1. Positive Self-Talk

Self-talk is one way to deal with stress. We all talk to ourselves; sometimes we talk out loud but usually we keep self-talk in our heads. Self-talk can be positive (“I can do this” or “Things will work out”) or negative (“I’ll never get well” or “I’m so stupid”).
Negative self-talk increases stress. Positive self-talk helps you calm down and control stress. With practice, you can learn to turn negative thoughts into positive ones.

For example:

Negative Positive
“I can’t do this.” “I’ll do the best I can.”
“Everything is going wrong.” “I can handle things if I take one step at a time.”
“I hate it when this happens.” “I know how to deal with this; I’ve done it before.”


To help you feel better, practice positive self-talk every day — in the car, at your desk, before you go to bed or whenever you notice negative thoughts.

Having trouble getting started? Try positive statements such as these:

  • “I’ve got this.”
  • “I can get help if I need it.”
  • “We can work it out.”
  • “I won’t let this problem get me down.”
  • “Things could be worse.”
  • “I’m human, and we all make mistakes.”
  • “Some day I’ll laugh about this.”
  • “I can deal with this situation.”Remember: Positive self-talk helps you relieve stress and deal with the situations that cause you stress.

2. Emergency Stress Stoppers

There are many stressful situations — at work, at home, on the road and in public places. We may feel stress because of poor communication, too much work and everyday hassles like standing in line. Emergency stress stoppers help you deal with stress on the spot.Try these emergency stress stoppers. You may need different stress stoppers for different situations and sometimes it helps to combine them.

  • Count to 10 before you speak.
  • Take three to five deep breaths.
  • Walk away from the stressful situation, and say you’ll handle it later.
  • Go for a walk.
  • Don’t be afraid to say “I’m sorry” if you make a mistake.
  • Set your watch five to 10 minutes ahead to avoid the stress of being late.
  • Break down big problems into smaller parts. For example, answer one letter or phone call per day, instead of dealing with everything at once.
  • Drive in the slow lane or avoid busy roads to help you stay calm while driving.
  • Smell a rose, hug a loved one or smile at your neighbor.
  • Consider meditation or prayer to break the negative cycle.

3. Finding Pleasure

When stress makes you feel bad, do something that makes you feel good. Doing things you enjoy is a natural way to fight off stress.You don’t have to do a lot to find pleasure. Even if you’re ill or down, you can find pleasure in simple things such as going for a drive, chatting with a friend or reading a good book.Try to do at least one thing every day that you enjoy, even if you only do it for 15 minutes.

Such as:

  1. Start an art project (oil paint, sketch, create a scrap book or finger paint with grandchildren).
  2. Take up a hobby, new or old.
  3. Read a favorite book, short story, magazine or newspaper.
  4. Have coffee or a meal with friends.
  5. Play golf, tennis, ping-pong or bowl.
  6. Sew, knit or crochet.
  7. Listen to music during or after you practice relaxation.
  8. Take a nature walk — listen to the birds, identify trees and flowers.
  9. Make a list of everything you still want to do in life.
  10. Watch an old movie on TV or rent a video.
  11. Take a class at your local college.
  12. Play cards or board games with family and friends.

4. Daily Relaxation

Relaxation is more than sitting in your favorite chair watching TV. To relieve stress, relaxation should calm the tension in your mind and body. Some good forms of relaxation are yoga, tai chi (a series of slow, graceful movements) and meditation.Like most skills, relaxation takes practice. Many people join a class to learn and practice relaxation skills.Deep breathing is a form of relaxation you can learn and practice at home using the following steps. It’s a good skill to practice as you start or end your day. With daily practice, you will soon be able to use this skill whenever you feel stress.

  1. Sit in a comfortable position with your feet on the floor and your hands in your lap or lie down. Close your eyes.
  2. Picture yourself in a peaceful place. Perhaps you’re lying on the beach, walking in the mountains or floating in the clouds. Hold this scene in your mind.
  3. Inhale and exhale. Focus on breathing slowly and deeply.
  4. Continue to breathe slowly for 10 minutes or more.
  5. Try to take at least five to 10 minutes every day for deep breathing or another form of relaxation.

©2014 American Heart Association, Inc. All rights reserved.


NFL Acknowledges, for First Time, Link between Football, Brain Disease

(ESPN) The NFL’s top health and safety officer acknowledged Monday there is a link between football-related head trauma and chronic traumatic encephalopathy, or CTE — the first time a senior league official has conceded football’s connection to the devastating brain disease.

The admission came during a roundtable discussion on concussions convened by the U.S. House of Representatives’ Committee on Energy and Commerce. Jeff Miller, the NFL’s senior vice president for health and safety, was asked by Rep. Jan Schakowsky, D-Ill., if the link between football and neurodegenerative diseases like CTE has been established.

“The answer to that question is certainly yes,” Miller said.

He said he based his assessment on the work of Dr. Ann McKee, a Boston University neuropathologist who has diagnosed CTE in the brains of 176 people, including those of 90 of 94 former NFL players. The disease can only be diagnosed after death.

“I think the broader point, and the one that your question gets to, is what that necessarily means, and where do we go from here with that information,”

Miller said, noting that little is known about the prevalence of the disease or the risk of incurring it.

On Tuesday, the NFL released this statement:

“The comments made by Jeff Miller yesterday accurately reflect the view of the NFL.”

In 2009, an NFL spokesman told the New York Times that it is

“quite obvious from the medical research that’s been done that concussions can lead to long-term problems.”

But when pressed by Congress and in interviews, NFL commissioner Roger Goodell and other league representatives have for years avoided taking a position, repeating that the league would let the medical community decide. The league had never expressly linked playing football to CTE.

During Super Bowl week, Dr. Mitch Berger, a San Francisco neurosurgeon who leads the NFL subcommittee on long-term brain injury, asserted that there is still no established link between football and CTE.

Schakowsky seized on Berger’s remarks during the informal discussion, in which several brain injury experts gathered around a rectangular table to discuss the science surrounding concussions.

“The NFL is peddling a false sense of security,” Schakowsky said.

“Football is a high-risk sport because of the routine hits, not just diagnosable concussions. What the American public need now is honesty about the health risks and clearly more research.”

She then asked McKee and Miller to answer “yes” or “no” about whether a connection between football and CTE has been established.

“I unequivocally think there’s a link between playing football and CTE,” McKee said.

“We’ve seen it in 90 out of 94 NFL players whose brains we’ve examined, we’ve found it in 45 out of 55 college players and six out of 26 high school players. No, I don’t think this represents how common this disease is in the living population, but the fact that over five years I’ve been able to accumulate this number of cases in football players, it cannot be rare. In fact, I think we are going to be surprised at how common it is.”

Schakowsky then turned to Miller. After acknowledging the link, he said: “But there’s also a number of questions that come with that.”

As he tried to continue, Schakowsky interrupted.

“Is there a link?” she said.

“Yes, sure,” Miller responded.

“Because we feel — well, I feel — that was not the unequivocal answer three days before the Super Bowl by Dr. Mitchel Berger,” Schakowsky said.

“Well, I’m not gonna speak for Dr. Berger,” Miller said.

Miller declined to elaborate on his remarks after the session. As reporters tried to ask follow-up questions, he left accompanied by a league spokeswoman, Jill Pike.

Hours after Miller’s comments, a lawyer representing seven former players objecting to the proposed settlement of the concussion lawsuit against the NFL sent a letter to the Third Circuit Court of Appeals.

The letter argued that Miller’s acknowledgement of a link and of McKee’s work reflects a “stark turn” from the league’s position, underscoring the objectors’ argument that CTE was not adequately addressed in the settlement. Attorney Steven Molo wrote that Miller’s comments “directly contradict” the NFL’s position in the case.

A judge previously approved a settlement between the league and thousands of former players who were suing the NFL for allegedly concealing the link between football and brain disease. The settlement is on hold while the objections are being considered.

The roundtable convened more than a dozen concussion experts and included representatives of the federal government, the military, the scientific community and the NCAA. Several of those present were affiliated with the NFL.

The conversation focused on the growing debate over the seriousness of the concussion issue, and what should be done about it. Some of the speakers said that awareness and treatment of concussions has never been better, and that the risks of playing contact sports like football have been overstated.

“The sky is not falling,” said Dr. David Cifu, chairman of Virginia Commonwealth University’s Department of Physical Medicine and Rehabilitation, noting that the risk of children incurring health issues such as obesity is greater by not playing sports than the risk of incurring a devastating concussion.

Others cautioned against conflating concussions with CTE, a distinct neurodegenerative disease that has only been found in people who have been exposed to head trauma, usually on multiple occasions.

“We don’t know how common this is; we are desperate to find a way to diagnose it in [living] people,” said Dr. Walter Koroshetz, director of the National Institute for Neurological Disorders and Stroke.

The roundtable comments came on the same day survey results were released showing that participation in youth tackle football had stabilized in the past year. After years of decline, participation among children ages 6-14 years old nudged up 1.9 percent to 2.1 million, according to the Sports & Fitness Industry Association.

Tom Cove, CEO of SFIA, urged caution in interpreting the results, noting that most youth sports benefitted in the past year from a demographic bulge. The year 2007 was a peak year for births, and those children are now at an age when youth football programs are offered for the first time.

More compelling to Cove was a significant jump in flag football participation, which rose 8.7 percent for the same age group.

“Preliminary indicators suggest flag for kids may be rising on a regional basis,” he said.

“For example, in the Pacific Northwest we’re hearing growth of youth flag leagues for young players, but not so much in South where traditional tackle remains strong.”


Steve Fainaru, ESPN Senior Writer. ESPN investigative reporters Mark Fainaru-Wada and Tom Farrey contributed to this report.

© 2016 ESPN Internet Ventures.


Antipsychotic Drugs Linked to Increased Mortality Among Parkinson’s Disease Patients

(ScienceDaily) At least half of Parkinson’s disease patients experience psychosis at some point during the course of their illness, and physicians commonly prescribe antipsychotic drugs, such as quetiapine, to treat the condition. However, a new study by researchers at the Perelman School of Medicine at the University of Pennsylvania, the University of Michigan Medical School, and the Philadelphia and Ann Arbor Veterans Affairs (VA) Medical Centers and suggests that these drugs may do significantly more harm in a subset of patients. The findings will be published in the March 21, 2016 issue of JAMA Neurology.

The researchers’ analysis of about 15,000 patient records in a VA database found that Parkinson’s patients who began using antipsychotic drugs were more than twice as likely to die during the following six months, compared to a matched set of Parkinson’s patients who did not use such drugs.

“I think that antipsychotic drugs should not be prescribed to Parkinson’s patients without careful consideration,” said senior author Daniel Weintraub, MD, who is an associate professor of Psychiatry and Neurology at Penn Medicine and a fellow in Penn’s Institute on Aging.

These findings are not the first to link antipsychotic drugs to increased mortality. Studies dating back to the early 2000s have found increased mortality with antipsychotic use among patients who have dementia in the general population. Since 2005 the FDA has mandated “black box” warnings on antipsychotic drug packaging, noting the apparently increased risk of death when these drugs are used in dementia patients.

Although most dementia cases are accounted for by Alzheimer’s disease, there are other forms of dementia, including one that eventually emerges in about 80 percent of Parkinson’s patients, usually many years after their Parkinson’s diagnosis. However, a study by Weintraub and colleagues in 2011 found that the FDA warnings had done little to curb antipsychotic prescriptions for Parkinson’s dementia patients.

For the new study, Weintraub and his collaborators examined the possibility that antipsychotic drug use is associated with higher mortality not just in Parkinson’s dementia patients, but in all Parkinson’s disease patients. Psychosis in Parkinson’s, although it is associated with dementia and later-stage disease, can occur even in the early stages of illness and in the absence of dementia. “It happens not uncommonly earlier in the course of the illness,” Weintraub said.

The underlying causes of psychosis in Parkinson’s are not well understood, but are thought to include the spread of the neurodegenerative disease process to certain brain areas, as well as particular or higher doses of Parkinson’s drugs that enhance dopamine function.

For the study, the researchers examined records from a large Veterans Affairs database, comparing a group of 7,877 Parkinson’s patients who were prescribed antipsychotic drugs at any time during 1999-2010 to an equal-sized “control group” of Parkinson’s patients who did not use antipsychotic drugs.

To reduce differences between the groups that could bias the comparison, the investigators paired each patient in the antipsychotic group with a control patient who was matched for age, gender, race, years since diagnosis, presence of dementia, and other relevant factors.

The analysis revealed that in the 180 days after they first took antipsychotic drugs, patients in the first group died in much larger numbers, compared with the matched control patients during the same periods. Overall the Parkinson’s patients who used antipsychotics had 2.35 times the mortality of the non-users.

The relative risk seemed to vary by the specific drug — for example, 2.16 times higher for quetiapine fumarate compared with non-treatment, 2.46 for risperidone, 2.79 for olanzapine, and 5.08 for haloperidol. First-generation or “typical” antipsychotics, which include haloperidol, collectively were associated with about 50 percent greater relative mortality risk, compared to more recently developed “atypical” antipsychotics such as risperidone and quetiapine.

Antipsychotic drugs have a variety of potential side-effects, including reduced alertness, increased risks of diabetes and heart disease, decreased blood pressure, and–with longer-term use — movement disorders that can resemble those seen in Parkinson’s.

The initial FDA warnings were based on findings of increased strokes among antipsychotic users. But researchers still do not fully understand why these drugs are linked to higher mortality in certain patient groups. “In this study we looked at the dataset for clues,” said Weintraub, “but the most common cause of death listed was ‘Parkinson’s disease’ — so there really wasn’t anything that pointed to a specific cause or mechanism.”

He and his colleagues are now conducting a follow-up study that might shed more light on that mechanism. They will examine the same VA database, looking not at mortality but at “morbidity” — disease diagnoses, injuries and other new episodes of ill-health–among Parkinson’s patients taking antipsychotic drugs, comparing them with the same matched controls.

For the present, Weintraub suggests that neurologists and other physicians should prescribe antipsychotics to Parkinson’s patients only after looking for other possible solutions, such as treating any co-morbid medical conditions associated with psychosis, reducing the dosage of dopamine replacement therapies, and simply managing the psychosis without antipsychotics.

“Antipsychotics should be used in these patients only when the psychosis is of clinical significance, and patients probably should not be left on these drugs long-term without re-evaluation,” Weintraub said.


Journal Reference

Daniel Weintraub, Claire Chiang, Hyungjin Myra Kim, Jayne Wilkinson, Connie Marras, Barbara Stanislawski, Eugenia Mamikonyan, Helen C. Kales. Association of Antipsychotic Use With Mortality Risk in Patients With Parkinson Disease. JAMA Neurology, 2016; DOI: 10.1001/jamaneurol.2016.0031

Other co-authors of the study were Jayne Wilkinson and Eugenia Mamikonyan of Penn and the Philadelphia VA; Claire Chiang, Hyungjin Myra Kim, Barbara Stanislawski, and Helen C. Kales of the University of Michigan and the VA Ann Arbor Healthcare System; and Connie Marras of the University of Toronto.

Funding was provided by the Veterans Health Administration (IIR 12-144-2).

Copyright 2015 ScienceDaily or by third parties, where indicated.


Association of Antipsychotic Use with Mortality Risk in Parkinson Disease

JAMA Neurol. 2016 Mar 21. doi: 10.1001/jamaneurol.2016.0031. [Epub ahead of print]

Association of Antipsychotic Use With Mortality Risk in Patients With Parkinson Disease.

Weintraub D1, Chiang C2, Kim HM3, Wilkinson J4, Marras C5, Stanislawski B2, Mamikonyan E6, Kales HC7.


As many as 60% of patients with Parkinson disease (PD) experience psychosis, 80% develop dementia, and the use of antipsychotics (APs) in the population with PD is common. The use of APs by patients with dementia in the general population is associated with increased mortality, but whether this risk extends to patients with PD remains unknown.


To determine whether AP use in patients with PD is associated with increased mortality.

Design, Setting, and Participants

This retrospective matched-cohort study used data from a Veterans Health Administration database from fiscal years 1999 to 2010 to examine the risk associated with AP use in a cohort of patients with idiopathic PD and recent stable physical health.

The rates of 180-day mortality were compared in 7877 patients initiating AP therapy and 7877 patients who did not initiate AP therapy (matched for age ±2.5 years, sex, race, index year, presence and duration of dementia, PD duration, delirium, hospitalization, Charlson Comorbidity Index, and new nonpsychiatric medications). Data were analyzed from October 19, 2012, to September 21, 2015.

Main Outcomes and Measures

Mortality rates at 180 days in those patients who initiated AP therapy compared with matched patients who did not use APs. Cox proportional hazards regression models were used with intent-to-treat (ITT) and exposure-only analyses.


The study population included 7877 matched pairs of patients with PD (65 women [0.8%] and 7812 men [99.2%] in each cohort; mean [SD] age, 76.3 [7.7] years for those who initiated AP therapy and 76.4 [7.6] years for those who did not).

Antipsychotic use was associated with more than twice the hazard ratio (HR) of death compared with nonuse (ITT HR, 2.35; 95% CI, 2.08-2.66; P < .001). The HR was significantly higher for patients who used typical vs atypical APs (ITT HR, 1.54; 95% CI, 1.24-1.91; P < .001).

Among the atypical APs used, HRs relative to nonuse of APs in descending order were 2.79 (95% CI, 1.97-3.96) for olanzapine, 2.46 (95% CI, 1.94-3.12) for risperidone, and 2.16 (95% CI, 1.88-2.48) for quetiapine fumarate.

Conclusions and Relevance

Use of APs is associated with a significantly increased mortality risk in patients with PD, after adjusting for measurable confounders. This finding highlights the need for cautious use of APs in patients with PD.

Future studies should examine the role of nonpharmacologic strategies in managing psychosis in PD. In addition, new pharmacologic treatments that do not increase mortality in patients with neurodegenerative diseases need to be developed.


© 2016 American Medical Association. All Rights Reserved.