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Identifying Pseudobulbar Affect in Alzheimer’s Disease and Dementia

US Neurology, 2014;10(1):10–4 DOI:


Pseudobulbar affect (PBA) can be challenging to differentiate from the symptoms of various neurological diseases with which it is associated. In patients with Alzheimer’s disease (AD) and dementia such a diagnosis can be particularly difficult as illustrated by a case of an elderly male with sudden tearful outbursts, which is reported and discussed here. PBA attacks are often incorrectly attributed to emotion or distress in response to memory loss or a result of depression or dementia. PBA is common, affecting between 10–40 % of people with AD but is frequently not detected or is misdiagnosed. Multiple authors have published clinical criteria for identifying PBA; in sum, it is described as a condition affecting the brain with episodes of laughing or crying that are sudden and unpredictable, occur without warning and are excessive, exaggerated, or not appropriate to the stimuli and are involuntary and difficult to control. Differentiating PBA from depression and other behavioral disturbances in AD and dementia is helpful to patients by identifying a specific cause of their symptoms and enabling appropriate management. Various different approaches have been taken in the treatment of PBA. A combination of dextromethorphan and quinidine hasbeen shown in well-controlled trials and in clinical use to control the symptoms of PBA associated with several neurological diseases including AD and to reduce the burden on patients and their caregivers.

Keywords: Pseudobulbar affect, Alzheimer’s disease, dementia, case report, differential diagnosis, epidemiology, diagnostic criteria, management
Disclosure: This project was commissioned and funded by Avanir Pharmaceuticals, Inc. The authors drafted the manuscript and are responsible for its content. Avanir Pharmaceuticals, Inc. provided editorial comments for author consideration. The authors had final control of the content and the information presented and any views expressed are those of the authors.
Acknowledgments: Editorial assistance was provided by James Gilbart, PhD, at Touch Medical Media. The authors would like to thank Ike Iheanacho, BSc, MB BS, for his review and editorial assistance.
Received: March 06, 2014 Accepted: March 26, 2014
Correspondence: William A Engelman, MD, 430 Bedford St, Ste 300, Lexington, MA 02420, US. E:
Support: The publication of this article was supported by Avanir Pharmaceuticals, Inc. The views and opinions expressed are those of the authors and not necessarily those of Avanir Pharmaceuticals, Inc.
An erratum to this article can be found below.

An estimated 5.3 million people in the US have Alzheimer’s disease (AD),1,2 the incidence of which increases with age.3 Defined as a ‘progressive mental deterioration manifested by loss of memory, ability to calculate, and visual-spatial orientation, confusion and disorientation;’4 the symptoms, clinical presentation, and prognosis of AD are well known among clinicians. It is also widely appreciated that AD may be associated with any of several neuropsychiatric symptoms including depression, agitation, anxiety, insomnia, and paranoia.

Given this potentially complex clinical background, onset of frequent crying episodes may seem neither unusual nor worthy of further exploration. However, this apparently sensible and pragmatic thinking is flawed, since it risks overlooking a major cause of such symptoms —pseudobulbar affect (PBA). Affecting as many as two in five people with AD5,6—but widely under-recognized by clinicians—this important condition must be considered when assessing patients like PJ (seeBox 1).

The Differential Diagnosis
The psychiatrist treating PJ assumed that he had depression associated with AD. However, the clinical symptoms described and the lack of therapeutic response raise the possibility of treatment-resistant depression or that depression is not the problem. A list of differentialdiagnoses would therefore include the following:

PJ’s crying episodes make it hard to ignore the possibility that he is depressed. However, it is important to note that frequent crying spells do not automatically indicate depression and that tearfulness is not a necessary or sufficient criteria in the Diagnostic and Statistical Manual of Mental Disorders, 5th Edition (DSM-V) for diagnosing major depressive disorder (MDD).7 Also, while many health care providers make the seemingly reasonable assumption that increased crying is a symptom of depression, there are limited data to support the idea that depressed patients have an increase in crying episodes.8–11 Evidence against the assumption includes the work of Rottenberg and colleagues,9 who compared crying episodes in patients with MDD to those in a control group of non-depressed participants, by using a cry-evoking stimulus (a sad movie). They found that crying was no more likely in the depressed than in the control group, who, surprisingly, showed greater crying-related emotional activity than the MDD group. Also, using patient self-reported episodes of crying to compare depressed versus non-depressed elderly individuals, Hastrup and colleagues11 found only a weak link in increased frequencies of crying episodes among elderly adults with depression, and concluded that crying could not be interpreted as a symptom or sign of depression.

Establishing if a patient with AD also has depression is further complicated by the overlapping features of the two conditions. For example, apathy and poor concentration are common symptoms found in dementia; anhedonia and nihilism also commonly occur in depression.7,12 Neurovegetative symptoms are common in both conditions and include disturbances in sleep and appetite, changes in weight , decreased sexual desire, decreased energy, psychomotor retardation or agitation, and poor concentration.13,14 Interestingly, depressed patients with apathy or neurovegetative symptoms may have fewer episodes of crying compared with someone without depression. When crying is caused by underlying depressive illness, it is associated with the patient’s reports of pervasive low mood.

Behavioral Disturbances
Behavioral disturbances are common in people with AD and other forms of dementia. For example, Lyketsos and colleagues studied patients with dementia using a screening questionnaire followed by a clinical assessment and found that 61 % exhibited one or more mental or behavioral disturbances within the past month, with apathy, depression, and agitation/aggression being the most common forms.15 Given their nature and high prevalence, behavioral disturbances could account for crying in patients with dementia.

Essential Crying
Essential crying is an uncommon disorder and is included for completeness.15 Those with essential crying have a lower threshold for weeping when compared with the normal population.14 This may be a variant of the emotional domain of temperament. Patients with the condition do not necessarily have an underlying neurological disorder.16,17 Crying would not be a new finding, but rather characteristic of the individual.

Pseudobulbar Affect
PBA is a disorder of regulation of emotional expression, caused by neurological disease or injury affecting the brain. PBA is characterized bysudden, uncontrollable episodes of crying, laughing, or both. These episodes are excessive, inconsistent with or disproportionate to circumstances or the patient’s underlying mood at the time.18

PJ’s symptoms are most likely to reflect either behavioral disturbances of dementia or PBA. The former will be familiar with clinicians who have experience caring for people with dementia, but what exactly is PBA and how can it be identified and managed?

  1. A lzheimer’s Association, 2010 Alzheimer’s disease facts and figures, Alzheimers Dement, 2010;6:158–94.
  2. C orrada MM, Brookmeyer R, Berlau D, et al., Prevalence of dementia after age 90: results from the 90+ study, Neurology, 2008;71:337–43.
  3. Gao S, Hendrie HC, Hall KS, et al., The relationships between age, sex, and the incidence of dementia and Alzheimer disease: a meta-analysis, Arch Gen Psychiatry, 1998;55:809–15.
  4. Stedman’s Concise Medical Dictionary for the Health Professions, Lippincott Williams & Wilkins, 2001.
  5. L opez OL, Gonzalez MP, Becker JT, et al., Symptoms of depression and psychosis in Alzheimer’s disease and frontotemporal dementia; exploration of underlying mechanisms, Neuropsychiatry Neuropsycol Behav Neurol, 1996;9:154–61.
  6. Starkstein SE, Migliorelli R, Teson A, et al., Prevalence and clinical correlates of pathological affective display in Alzheimer’s disease, J Neurol Neurosurg Psychiatry, 1995;59:55–60.
  7. A merican Psychiatric Association, Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition, Arlington, VA: American Psychiatric Publishing, 2013.
  8. Rottenberg J, Cevaal A, Vingerhoets AJ, Do mood disorders alter crying? A pilot investigation, Depress Anxiety, 2008;25:E9–15.
  9. Rottenberg J, Gross JJ, Wilhelm FH, et al., Crying threshold and intensity in major depressive disorder, J Abnorm Psychol, 2002;111:302–12.
  10. Vingerhoets AJ, Rottenberg J, Cevaal A, et al., Is there a relationship between depression and crying? A review, Acta Psychiatr Scand, 2007;115:340–51.
  11. H astrup JL, Baker JG, Kraemer DL, et al., Crying and depression among older adults, Gerontologist, 1986;26:91–6.
  12. A ndrew LB, Depression and suicide, Electronic Source, 2012. Avaialble at: overview#showall (accessed March 29, 2014).
  13. L yness JM, Clinical manifestations and diagnosis of depression, Electronic Source, 2013. http://www.uptodate. com/contents/clinical-manifestations-and-diagnosis-ofdepression? source=search_result&search=4+neurovegetative& selectedTitle=1~15 (accessed March 29, 2014).
  14. McKhann G, Drachman D, Folstein M, et al., Clinical diagnosis of Alzheimer’s disease: report of the NINCDS-ADRDA Work Group under the auspices of Department of Health and Human Services Task Force on Alzheimer’s Disease, Neurology, 1984;34:939–44.
  15. L yketsos CG, Steinberg M, Tschanz JT, et al., Mental and behavioral disturbances in dementia: findings from the Cache County Study on Memory in Aging, Am J Psychiatry, 2000;157:708–14.
  16. A rciniegas DB, Lauterbach EC, Anderson KE, et al., The differential diagnosis of pseudobulbar affect (PBA). Distinguishing PBA among disorders of mood and affect. Proceedings of a roundtable meeting, CNS Spectr, 2005;10:1–14; quiz 5–6.
  17. Green RL, McAllister TW, Bernat JL, A study of crying in medically and surgically hospitalized patients, Am J Psychiatry, 1987;144:442–7.
  18. Rosen HJ, Cummings J, A real reason for patients with pseudobulbar affect to smile, Ann Neurol, 2007;61:92–6.
  19. C ummings J, Gilbart J, Andersen G, Pseudobulbar affect – a disabling but under-recognised consequence of neurological disease and brain injury, Eur Neurol Rev, 2013;8:74–81.
  20. Schiffer R, Pope LE, Review of pseudobulbar affect including a novel and potential therapy, J Neuropsychiatry Clin Neurosci, 2005;17:447–54.
  21. C hoi-Kwon S, Han SW, Kwon SU, et al., Fluoxetine treatment in poststroke depression, emotional incontinence, and anger proneness: a double-blind, placebo-controlled study, Stroke, 2006;37:156–61.
  22. Kim JS, Post-stroke emotional incontinence after small lenticulocapsular stroke: correlation with lesion location, J Neurol, 2002;249:805–10.
  23. Moore SR, Gresham LS, Bromberg MB, et al., A self report measure of affective lability, J Neurol Neurosurg Psychiatry, 1997;63:89–93.
  24. Parvizi J, Anderson SW, Martin CO, et al., Pathological laughter and crying: a link to the cerebellum, Brain, 2001;124:1708–19.
  25. Balakrishnan P, Rosen H, The causes and treatment of pseudobulbar affect in ischemic stroke, Curr Treat Options Cardiovasc Med, 2008;10:216–22.
  26. Parvizi J, Arciniegas DB, Bernardini GL, et al., Diagnosis and management of pathological laughter and crying, Mayo Clin Proc, 2006;81:1482–6.
  27. Parvizi J, Coburn KL, Shillcutt SD, et al., Neuroanatomy of pathological laughing and crying: a report of the American Neuropsychiatric Association Committee on Research, J Neuropsychiatry Clin Neurosci, 2009;21:75–87.
  28. Siddiqui M, Kirsch-Darrow L, Fernandez H, et al., Prevalence of pseudobulbar affect in movement disorders and its mood correlates: a prospective study of 754 consecutive patients [abstract], Neurology, 2006;66:A369. Abstract P06.156.
  29. Siddiqui MS, Fernandez HH, Garvan CW, et al., Inappropriate crying and laughing in Parkinson disease and movement disorders, World J Biol Psychiatry, 2009;10:234–40.
  30. Strowd RE, Cartwright MS, Okun MS, et al., Pseudobulbar affect: prevalence and quality of life impact in movement disorders, J Neurol, 2010;257:1382–7.
  31. Brooks BR, Crumpacker D, Fellus J, et al., PRISM: a novel research tool to assess the prevalence of pseudobulbar affect symptoms across neurological conditions, PLoS One, 2013;8:e72232.
  32. Work SS, Colamonico JA, Bradley WG, et al., Pseudobulbar affect: an under-recognized and under-treated neurological disorder, Adv Ther, 2011;28:586–601.
  33. Poeck K, Pathophysiology of emotional disorders associated with brain damage, Handbook of Clinical Neurology, 1969;3:343–67.
  34. H ouse A, Dennis M, Molyneux A, et al., Emotionalism after stroke, BMJ, 1989;298:991–4.
  35. Kim JS, Choi-Kwon S, Poststroke depression and emotional incontinence: correlation with lesion location, Neurology, 2000;54:1805–10.
  36. C ummings JL, Arciniegas DB, Brooks BR, et al., Defining and diagnosing involuntary emotional expression disorder, CNS Spectr, 2006;11:1–7.
  37. Press D, Alexander M, Treatment of behavioral symptoms related to dementia, Electronic Source, 2012. http://www. to-dementia?source=see_link (accessed March 29, 2014).
  38. Warden V, Hurley AC, Volicer L, Development and psychometric evaluation of the Pain Assessment in Advanced Dementia (PAINAD) scale, J Am Med Dir Assoc, 2003;4:9–15.
  39. Pioro EP, Brooks BR, Cummings J, et al., Dextromethorphan plus ultra low-dose quinidine reduces pseudobulbar affect, Ann Neurol, 2010;68:693–702.
  40. A vanir Pharmaceuticals Inc, Nuedexta® prescribing Information, 2010. Available at: Prescribing%20Information.pdf (accessed February 27, 2014).
Keywords: Pseudobulbar affect, Alzheimer’s disease, dementia, case report, differential diagnosis, epidemiology, diagnostic criteria, management
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