Delirium (from Hospitalization or Illness) + Memory Loss

This press release out of Beth Israel Deaconess Medical Center in Boston will be of interest to those dealing with dementia. The press release reports on a study that “confirms that an episode of delirium rapidly accelerates cognitive decline and memory loss in Alzheimer’s patients.” “Delirium often develops in elderly patients during hospitalization or serious illness, and this acute state of confusion and agitation has long been suspected of having ties to Alzheimer’s disease and other dementias.”

http://www.bidmc.org/News/InResearch/20 … entia.aspx

Delirium Accelerates Memory Loss in Patients With Alzheimer’s Disease
Acute state of confusion and disorientation often complicates hospitalizations for patients with dementia

Date: 5/4/2009
Beth Israel Deaconess Medical Center, Boston, MA
Press Release

BOSTON – Delirium often develops in elderly patients during hospitalization or serious illness, and this acute state of confusion and agitation has long been suspected of having ties to Alzheimer’s disease and other dementias. Now a study led by researchers at Beth Israel Deaconess Medical Center (BIDMC) and Hebrew Senior Life confirms that an episode of delirium rapidly accelerates cognitive decline and memory loss in Alzheimer’s patients. The findings are reported in the May 5 issue of the journal Neurology.

“The cognitive rate of decline was found to be three times more rapid among those Alzheimer’s patients who had had an episode of delirium than among those who did not have such a setback,” according to lead author Tamara Fong, MD, a staff neurologist at BIDMC and Assistant Scientist at the Institute for Aging Research, Hebrew Senior Life. “In other words, the amount of decline you might expect to see in an Alzheimer’s patient over the course of 18 months would be accelerated to 12 months following an episode of delirium.”

Alzheimer’s disease is an irreversible, progressive form of dementia that gradually destroys a person’s ability to carry out even the simplest of tasks, and affects as many as 4.5 million individuals in the U.S. according to figures from the National Institute on Aging. There is currently no cure for Alzheimer’s disease.

Delirium, on the other hand, is a potentially preventable condition, which often develops following a medical disturbance, surgery or infection and is estimated to affect between 14 percent and 56 percent of all hospitalized elderly patients.

The investigators performed a secondary analysis of data gathered from 408 patients examined between 1991 and 2006 at the Massachusetts Alzheimer’s Disease Research Center (MADRC). Over this 15-year period, MADRC staff conducted a number of memory tests on patients. Testing was done on at least three occasions, separated by intervals of approximately six months. Seventy-two of the participants developed delirium during the course of the study.

In their final analysis, the authors found that among patients who developed delirium, the average decline on cognitive tests was 2.5 points per year at the beginning of the study; following an episode of delirium, decline nearly doubled to 4.9 points per year.

“Although each dementia patient declines at his or her own individual rate, the results of our study tell us that this rate can increase three-fold following an episode of delirium,” says Fong. “As an example, suppose an Alzheimer’s patient begins with mild symptoms, such as forgetting appointments or details of conversations, but over a period of the next 18 months, loses the ability to identify relatives, becomes lost while driving familiar routes, or can no longer balance a checkbook or manage financial transactions. This same patient, were he or she to experience an episode of delirium, might experience this same rate of decline in only 12 months.”

While further investigations are needed to determine the mechanism behind this turn-of-events, Fong explains that delirium may, in fact, be a key link in a chain of events that results in injury to brain cells. “Older patients may be at greater risk of developing delirium – particularly in the hospital setting – because they tend to have less ‘reserve’ or ability to compensate in settings of increased stress. Consequently, infections, new medications and other stressors put the patient at risk for delirium.”

All elderly patients, but particularly patients who have already been diagnosed with Alzheimer’s disease, can benefit from a number of preventive measures if they are hospitalized, notes Fong.

“As much as possible, it’s important to try and orient the patient to his or her surroundings [i.e. frequently remind the patient that he or she is in the hospital], to allow for as much uninterrupted sleep as possible by not waking patients to take vital signs or do blood draws at night, and to get patients out of bed and walking as soon as their medical condition allows,” notes Fong. Also, important, she adds, is to avoid use of unnecessary medications.

“Twenty percent of all elderly patients who develop delirium go on to experience complications, whether it’s a prolonged hospital stay, a move to a rehabilitation center or long-term care facility, or even death,” notes Fong. “Our current study now shows that delirium can also adversely impact the state of cognitive decline in patients with Alzheimer’s disease. Because up to 40 percent of delirium episodes can be prevented, taking steps to avoid delirium could result in significant improvements.”

This study was funded, in part, by grants from the Massachusetts Alzheimer’s Disease Research Center, the National Institute on Aging, and the Alzheimer’s Association, and the VA Rehabilitation Career Development Award.

Study coauthors include BIDMC investigators Edward Marcantonio and Sharon Inouye; Hebrew Senior Life investigators Richard Jones, Peilin Shi, James Rudolph, Frances Yang and Douglas Kiely; and Liang Yap of Massachusetts General Hospital.

Beth Israel Deaconess Medical Center is a patient care, teaching and research affiliate of Harvard Medical School and consistently ranks in the top four in National Institutes of Health funding among independent hospitals nationwide. BIDMC is a clinical partner of the Joslin Diabetes Center and a research partner of the Dana-Farber/Harvard Cancer Center. BIDMC is the official hospital of the Boston Red Sox. For more information, visit www.bidmc.org.


 

There’s a 5-minute NPR story today on delirium. Apparently 2 million seniors a year (or about one-third) who go into the hospital are affected by delirium. Here’s an enlightening excerpt:

“My father wound up getting delirious even when I was there at his bedside,” [Dr. Sharon Inouye, a geriatrician] says. “I’m an expert in delirium, and I couldn’t prevent it from happening.”

Inouye attributes it to hospital care that has become complex and fragmented.

“There were just so many physicians taking care of my father, so many medications,” Inouye says. “It was really hard for me to keep track of everything. You know, I knew there were certain medications he couldn’t tolerate, and I told one group of physicians, and then another group of physicians would prescribe it. And so it really just was quite eye-opening for me.”

If one of the world’s leading researchers on delirium couldn’t protect her own father, the average American might feel helpless, too.

Here’s the link and most of the story (the introduction isn’t available in text form):

http://www.npr.org/templates/story/stor … =111623212

Treating Delirium: An Often Missed Diagnosis
by Joseph Shapiro
August 10, 2009
NPR Morning Edition

Virginia Helton says her husband is a “brilliant” man. He’s a scientist who can explain complex chemistry and physics. But when he was in the hospital last February, she didn’t recognize the man acting so bizarrely — talking wild nonsense and taking off his clothes.

Earle Helton, 79, was diagnosed with delirium, a sudden and frightening onset of confusion. A common but often unrecognized problem in hospitalized elderly people, delirium is estimated to affect more than 2 million seniors a year.

“I was feeling very scared,” his wife says. “It was very disturbing to see him in all this confusion with disordered speech.”

“I remember quite vividly my desire to escape, and [I] was proposing all sorts of fantastic schemes, according to the kids, as to how I could get out and get out of the hospital,” Earle Helton says. “As a matter of fact, I ended up executing that on at least one occasion and managed to get through the hospital and underneath one of the surgical beds.”

Virginia Helton says staff at the hospital “tied his hands down because he kept trying to get out of the bed, and that made him furious. And they did that several times when he was in this state of delirium.”

Dr. Sharon Inouye was working at the Boston hospital where Helton was a patient. She recognized he was on an anti-seizure medication that could cause confusion. She stopped the medicine, but it took a few days for the drug to clear his system and the delirium to stop.

Inouye, a geriatrician at Harvard Medical School and Hebrew Senior Life, says it’s easy for doctors to miss delirium. Most of the time, a person with delirium is inattentive and may have trouble following a conversation. Sometimes, the symptoms are more obvious.

“What we look for is a person who is having a lot of difficulty answering questions,” Inouye says. “They often will not make sense. They may hallucinate. They may be very agitated. They may have a totally different personality. You know, very often family members will say to me: ‘He’s nothing like that at home.’ ”

Inouye saw delirium in her own father, who was also a physician.

“My father wound up getting delirious even when I was there at his bedside,” she says. “I’m an expert in delirium, and I couldn’t prevent it from happening.”

Inouye attributes it to hospital care that has become complex and fragmented.

“There were just so many physicians taking care of my father, so many medications,” Inouye says. “It was really hard for me to keep track of everything. You know, I knew there were certain medications he couldn’t tolerate, and I told one group of physicians, and then another group of physicians would prescribe it. And so it really just was quite eye-opening for me.”

If one of the world’s leading researchers on delirium couldn’t protect her own father, the average American might feel helpless, too.

Still, there are precautions a patient’s family can take. Family members can start by becoming more aware of the drugs that cause delirium, says geriatrician Malaz Boustani at Indiana University School of Medicine.

One class of medications that can be a big trigger is anti-cholinergic medications or common prescription and over-the-counter drugs such as some sleeping pills, asthma medications and antidepressants.

It’s also important for older patients in the hospital to keep using their eyeglasses and hearing aids and be allowed to sleep through the night, says Boustani. Delirium can be triggered by a state of confusion, and these things help maintain a more consistent environment.

Boustani recently studied 1,000 senior citizens who came to an Indianapolis hospital. One-third developed delirium. And those who spent more time in the hospital had a higher risk of going to a nursing home or of dying.

Doctors often dismiss delirium, Boustani says, because they think it’s just dementia in older people. The two are different. Delirium is a temporary form of cognitive impairment, whereas dementia is a more long-term problem that involves issues with at least two brain functions, such as memory loss along with impaired judgment or language.

Still, there’s a link between dementia and delirium.

“What we found [is] that if you develop delirium in the hospital and we follow you up to five years, the odds of developing dementia or Alzheimer’s disease is five times more,” Boustani says. “And the question is: Is it the delirium itself that caused toxic insult to the brain and then triggers spiral evolution to develop dementia? Or was the delirium simply a positive stress test for dementia?”

Boustani suspects that an episode of delirium shows dementia that already exists or is developing. But other researchers suspect that getting delirium in the hospital can cause long-term dementia.

That’s one more reason why it’s important for researchers, doctors and patients to better understand delirium that occurs in the hospital — and how to avoid it. Boustani says studying delirium appeals to him because it’s one condition in the elderly that can be reversed, not to mention something he just might encounter in the future.

“It’s a fulfilling feeling as a doctor,” Boustani says. “At the same time, I want to live as long as possible.”

He says that if he lives that good, long life, the chances are that he’ll be an elderly man in a hospital one day. “I want to be proactive and make sure the system is ready for me.”

Neuropsychological decline in CBD and other FTLD subtypes

This abstract was published today on PubMed. CBD is considered a subtype of FTLD (frontotemporal lobar degeneration). This Drexel University study assessed whether the patterns of neuropsychological impairment in CBD, three other FTLD subtypes, and AD remain distinct over the duration of the disease or “devolve into a common, undifferentiated neuropsychological state.” The researchers found that the patterns remained distinct. For CBD, patients “presented with performance on visuoconstructional tests.” A quick Google search revealed several visuoconstructional tests including Constructional Praxis, Stick Design, and Bicycle Drawing. Perhaps the clock test is also a visuoconstructional test.
Robin

Neuropsychology. 2009 May;23(3):337-46.

Neuropsychological decline in frontotemporal lobar degeneration: A longitudinal analysis.

Libon DJ, Xie SX, Wang X, Massimo L, Moore P, Vesely L, Khan A, Chatterjee A, Coslett HB, Hurtig HI, Liang TW, Grossman M.
Department of Neurology, Drexel University College of Medicine.

Few studies have assessed whether the patterns of neuropsychological impairment in patients with different frontotemporal lobar degeneration (FTLD) subtypes remain distinct over the duration of their illness or devolve into a common, undifferentiated neuropsychological state.

A longitudinal neuropsychological analysis was obtained over 100 months assessing executive control, language/naming, and visuoconstruction in 441 patients diagnosed with Alzheimer’s disease (AD) and four FTLD subtypes, i.e., a social comportment/dysexecutive (SOC/EXEC) disorder; progressive non-fluent aphasia (PNFA); semantic dementia (SemD); and corticobasal degeneration (CBD).

Initial group differences on each measure were maintained over the duration of illness, including several double dissociations. For example, AD patients exhibited a decline in ‘animal’ fluency; PNFA patients had difficulty on tests of executive control, SemD maintained their impairment on tests of naming, and CBD had presented with performance on visuoconstructional tests.

None of the group by neuropsychological task interactions evaluating longitudinal decline was significant, suggesting that performance does not converge onto a common subtype over time. These data indicate that distinct patterns of neuropsychological impairment are maintained longitudinally, reflecting the unique anatomic distribution of relative disease burden in AD and FTLD.

PubMed ID#: 19413447 (see pubmed.gov for abstract only)

Cerebellar involvement in PSP (22 confirmed patients)

Clinicopathological studies are the gold standard for any medical research. These sorts of studies find brains of those with certain diseases and then refer back to the patients’ medical records to see what observations can be made and lessons learned.

This Japanese clinicopathological study looks at 22 patients with path-confirmed PSP. I think the most recent Williams/UK study looked at 85 patients.

“10 patients were categorized as having RS, and 8 were categorized as having PSP-P. Four patients presenting with cerebellar ataxia or cerebral cortical signs were categorized as having unclassifiable PSP. Among them, 3 developed cerebellar ataxia as the initial and principal symptom.” This study “demonstrates that PSP patients manifest cerebellar ataxia.” (Dr. David Williams came up with the classification of RS or Richardson’s Syndrome and PSP-P or PSP-Parkinsonism. His research since 2005 or so describes these two main types of PSP.)

Robin

Movement Disorders. 2009 May 1. [Epub ahead of print]

Cerebellar involvement in progressive supranuclear palsy: A clinicopathological study.

Kanazawa M, Shimohata T, Toyoshima Y, Tada M, Kakita A, Morita T, Ozawa T, Takahashi H, Nishizawa M.
Department of Neurology, Brain Research Institute, Niigata University, Niigata, Japan.

The clinical heterogeneity of progressive supranuclear palsy (PSP), which is classified as classic Richardson’s syndrome (RS) and PSP-Parkinsonism (PSP-P), has been previously discussed. We retrospectively analyzed 22 consecutive Japanese patients with pathologically proven PSP to investigate the clinicopathological heterogeneity. We investigated the clinical features both early in and at any time during the disease course. The pathological severities of neuronal loss with gliosis and tau pathology were also evaluated. On the basis of the clinical features, 10 patients were categorized as having RS, and 8 were categorized as having PSP-P. Four patients presenting with cerebellar ataxia or cerebral cortical signs were categorized as having unclassifiable PSP. Among them, 3 developed cerebellar ataxia as the initial and principal symptom. Notably, tau-positive inclusion bodies in Purkinje cells were significantly more frequently observed in the patients with cerebellar ataxia than in those without cerebellar ataxia. All the patients with cerebellar ataxia exhibited more neuronal loss with gliosis and higher densities of coiled bodies in the cerebellar dentate nucleus than those without cerebellar ataxia. This study confirms the wide spectrum of clinicopathological manifestations associated with PSP regardless of different ethnic origin, and demonstrates that PSP patients manifest cerebellar ataxia.

PubMed ID#: 19412943 (see pubmed.gov for abstract only)

Sleep Disorders Affect Majority of Elderly (Mayo Rochester)

This press release out of Mayo Rochester (MN) is about a new study in one Minnesota county that showed that “59 percent of 892 people age 70-89 had signs of at least one recognized sleep disorder other than insomnia. The most common disorder, reported by 32 percent of study participants, was sleep-related leg cramps. … Obstructive sleep apnea–characterized by breathing pauses during sleep–occurred in 17.6 percent of participants. … A movement disorder known as REM sleep behavior disorder (RBD) occurred in about 9 percent of participants. This happens when sleepers appear to act out their dreams. … Restless legs syndrome–an irresistible urge to move legs associated with uncomfortable sensations–was suggested in about 8 percent of the study group.”

A Mayo Rochester neurologist who is also a sleep expert, Dr. Brad Boeve, had these comments about the study findings: “Perhaps the biggest surprise of the study is the high frequency of probable RBD in these participants.” The only study on the epidemiology of RBD in the population shows a prevalence of 0.5 percent, whereas these findings suggest a frequency of 9 percent in the 70-89 age range, he says. The frequency matters, he adds, because earlier research by our and other groups has suggested that those with RBD have an increased likelihood of developing a neurologic disorder such as Parkinson’s disease or Lewy body dementia in the future. “One ultimate goal is that once medications are developed that affect the biology of Parkinson’s disease and Lewy body dementia, we hope that they may be used in appropriately-identified individuals with RBD to delay the onset or prevent the development of symptoms associated with those disorders,” Dr. Boeve says.

In our local support group, many people with MSA and LBD have RBD. RBD can be confirmed with a polysomnogram, or a special sleep study that measures eye, leg, and other movements and records breathing and brain activity.

Here are two online video resources about this story:

http://www.youtube.com/watch?v=Kx9aDxv7YyI –> YouTube video of Dr. Jennifer Molano speaking about the study (2.5 minutes)

http://newsblog.mayoclinic.org/2009/04/ … nic-study/ –> scroll down to the Journalists section where you’ll find .wmv and .mp3 files on a study overview, study findings, and patient message

The press release is copied below.

http://www.mayoclinic.org/news2009-rst/5256.html

Sleep Disorders Affect Majority of Elderly Participants in a Large Mayo Clinic Study
Tuesday, April 28, 2009
Mayo Clinic Rochester Press Release

SEATTLE — Sleep disorders are common in the elderly, say researchers from Mayo Clinic who studied a large number of people in this age group in one Minnesota county.

At the 2009 American Academy of Neurology Annual Meeting in Seattle on April 28, the researchers report that 59 percent of 892 people age 70-89 had signs of at least one recognized sleep disorder other than insomnia. The most common disorder, reported by 32 percent of study participants, was sleep-related leg cramps.

The researchers say that their study is one of the first to look at a broader spectrum of sleep disorders in a community’s elderly, and understanding the prevalence of these problems may lead to increased diagnosis followed by beneficial treatment.

“All of these sleep disorders can disrupt a person’s quality of life, because they affect sleep,” says the study’s lead researcher, Jennifer Molano, M.D., a behavioral neurology fellow in the Department of Neurology. “But if these problems are recognized, an accurate diagnosis could lead to successful treatment.”

The research is part of Mayo Clinic’s Study of Aging, a multidisciplinary effort to understand age-related diseases and cognitive functioning. The bed partners of study participants in Olmsted County, Minn., home of Mayo Clinic, answered a questionnaire about how well their partners slept.

The researchers identified these other commonly reported disrupters of sleep:

Obstructive sleep apnea–characterized by breathing pauses during sleep–occurred in 17.6 percent of participants. Men were four times more likely to have features of obstructive sleep apnea compared to women.

Periodic, involuntary movements in the legs or arms during sleep were experienced by 17.4 percent.

A movement disorder known as REM sleep behavior disorder (RBD) occurred in about 9 percent of participants. This happens when sleepers appear to act out their dreams. In this study, men were twice as likely to exhibit recurrent dream enactment behavior as women. The disorder was also seen more often in people age 80 or older who had worsening cognitive impairment or dementia.

Restless legs syndrome–an irresistible urge to move legs associated with uncomfortable sensations–was suggested in about 8 percent of the study group.

Only 0.2 percent of participants were found to walked in their sleep.

“Perhaps the biggest surprise of the study is the high frequency of probable RBD in these participants,” says Bradley Boeve, M.D., a Mayo Clinic neurologist and one of several study investigators.The only study on the epidemiology of RBD in the population shows a prevalence of 0.5 percent, whereas these findings suggest a frequency of 9 percent in the 70-89 age range, he says. The frequency matters, he adds, because earlier research by our and other groups has suggested that those with RBD have an increased likelihood of developing a neurologic disorder such as Parkinson’s disease or Lewy body dementia in the future. “One ultimate goal is that once medications are developed that affect the biology of Parkinson’s disease and Lewy body dementia, we hope that they may be used in appropriately-identified individuals with RBD to delay the onset or prevent the development of symptoms associated with those disorders,” Dr. Boeve says.

The researchers hope to follow up these results with a validation study using a polysomnogram (or sleep study), which measures eye, leg, and other movements and records breathing and brain activity.

The study was funded by grants from the National Institute on Aging, the Robert H. and Clarice Smith and Abigail Van Buren Alzheimer’s Disease Research Program of the Mayo Foundation. Researchers at Mayo Clinic campus in Florida assisted in the study.

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About Mayo Clinic

Mayo Clinic is the first and largest integrated, not-for-profit group practice in the world. Doctors from every medical specialty work together to care for patients, joined by common systems and a philosophy of “the needs of the patient come first.” More than 3,300 physicians, scientists and researchers and 46,000 allied health staff work at Mayo Clinic, which has sites in Rochester, Minn., Jacksonville, Fla., and Scottsdale/Phoenix, Ariz. Collectively, the three locations treat more than half a million people each year. To obtain the latest news releases from Mayo Clinic, go to www.mayoclinic.org/news. For information about research and education visit www.mayo.edu. MayoClinic.com is available as a resource for your health stories.