Pseudobulbar Affect in Alzheimer’s Disease

Pseudobulbar affect (PBA) is a condition that causes sudden and uncontrollable bursts of emotion, such as laughing or crying, that may not reflect how a person is actually feeling.

About two million people living in the U.S. are diagnosed with PBA, but more than seven million people are thought to have symptoms suggestive of PBA. Symptoms of PBA were found to be present in about 29% of Alzheimer’s disease patients.

Patients who have neurological conditions such as Alzheimer’s disease, Parkinson’s diseasemultiple sclerosis, traumatic brain injury, and strokes are all at risk of developing PBA. PBA is a distinct clinical condition, and not part of the underlying neurological disease.

Causes

The brain is made of two main parts, the cerebral cortex (the main bulk of the brain) and the brainstem (the stalk or “bulb” of the brain). The neurological pathways between these two parts are important in regulating mood and emotion. PBA develops when a neurological disease or brain injury disrupts this connection.

Neurotransmitters — chemical messengers that allow nerve cells to communicate — such as serotonin, dopamine, and glutamate, also may play a role in PBA.

Serotonin is involved in the regulation of emotional expression. The deficiency of this neurotransmitter is thought to contribute to dysfunction that leads to PBA.

Dopamine plays an important role in several brain functions, such as motor control, motivation, reward, and cognitive function. Although little is known about the role of dopamine in PBA, there is some evidence supporting the role of this signaling molecule in triggering inappropriate outbursts.

Glutamate is the main excitatory neurotransmitter in the central nervous system and is involved in learning, memory, and development of nerve cells. Excessive levels of glutamate in certain brain circuits are also thought to contribute to outbursts.

Symptoms

Those with PBA experience frequent and sudden, inappropriate spells of laughter or crying. These emotions may occur as an exaggerated response to situations, such as weeping instead of a frown when given bad news. Patients  also may suddenly switch between laughing and crying, or vice versa.

These bursts may occur in ways that are inappropriate and confusing. For example, a person may cry at good news or laugh during a funeral. Patients have no control over the episodes, which may appear at any time and occasionally without any obvious trigger.

Because crying is a prominent feature of PBA, patients may be mistakenly thought to have depression. However, people with PBA experience only short episodes in which they express sadness — lasting seconds to minutes — and do not persistently feel sad or depressed. Other symptoms common in depression, such as disturbed sleep or sleeping patterns or a loss of appetite, also are not seen in those with PBA.

Living with PBA

PBA can greatly impair a person’s social life. Unpredictable emotional outbursts can result in people developing phobias, causing them to isolate at home. Educating family and friends about PBA can help in understanding the nature of this condition.

During episodes of emotional outburst, patients may find it helpful to take slow, deep breaths and try to relax until the episode passes. Changing body position (standing when previously sitting down and vice versa) also may help them to cope with such attacks.

Treatment

Nuedexta (dextromethorphan and quinidine) is the first, and currently only, treatment approved by the U.S. Food and Drug Administration (FDA) for PBA. It was tested in people with PBA secondary to dementia and brain injuries and reported to be effective.

AVP-786, a second-generation version of Nuedexta, is under clinical investigation to assess its role in treating agitation in Alzheimer’s patients. Like Nuedexta, AVP-786 is a combination of dextromethorphan and quinidine, but it also contains deuterium, an isotope of hydrogen. A Phase 3 clinical trial (NCT03393520) is evaluating the safety and efficacy of two different doses of AVP-786 in patients with Alzheimer’s dementia.

Antidepressants, such as selective serotonin reuptake inhibitors (SSRIs) and tricyclic antidepressants (TCAs), may be used to control PBA episodes. These therapies usually are taken at lower doses compared to those used to treat depression.

Occupational therapy also may help patients develop strategies to complete daily tasks.

 

Last updated: Jan. 26, 2022, by Teresa Carvalho MSc

 


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