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Prevalence, neurobiology, and treatments for apathy in prodromal dementia

Published online by Cambridge University Press:  18 April 2017

Chelsea Sherman ,
Celina S. Liu ,
Nathan Herrmann  and
Krista L. Lanctôt
Chelsea Sherman
Affiliation:
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Toronto, Ontario, Canada
Celina S. Liu
Affiliation:
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Toronto, Ontario, Canada
Nathan Herrmann
Affiliation:
Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
Krista L. Lanctôt*
Affiliation:
Department of Pharmacology and Toxicology, University of Toronto, Toronto, Ontario, Canada Neuropsychopharmacology Research Group, Hurvitz Brain Sciences Program Sunnybrook Research Institute, Toronto, Ontario, Canada Department of Psychiatry, University of Toronto, Toronto, Ontario, Canada
*
Correspondence should be addressed to: Krista L. Lanctôt, Sunnybrook Health Sciences Centre, 2075 Bayview Ave, Room FG08, Toronto, ON. M4N 3M5, Canada. Phone: +416-480-6100 ext. 2241; Fax: +416-480-6022. Email: [email protected].
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Abstract

Background:

Apathy, characterized by diminished motivation, is a highly prevalent neuropsychiatric symptom in dementia. However, there is a substantial knowledge gap with regard to prevalence rates, neurobiological underpinnings, and effective treatments for apathy in pre-dementia states, including mild cognitive impairment (MCI) and mild behavioral impairment (MBI).

Methods:

We conducted a comprehensive literature search using MEDLINE, Embase, and PsycINFO databases to identify available research on apathy in prodromal dementia.

Results:

Apathy has consistently been detected in individuals with MCI with varying prevalence rates, and only recently has literature discussed the prevalence of apathy in MBI. Few pharmacological treatments have been utilized for apathy, with galantamine and risperidone showing mild reductions in apathetic behaviors. Non-pharmacological interventions in prodromal dementia are beginning to be explored and show promise, but few studies have replicated those results.

Discussion:

More comprehensive guidelines for diagnosing apathy and further research investigating neurobiological mechanisms of apathy in MCI and MBI are required in order to effectively treat apathetic patients in prodromal dementia.

Keywords

mild cognitive impairmentmild behavioral impairmentpre-dementia syndromesprodromal dementiaapathydecreased motivation
Type
Review Article
Information
International Psychogeriatrics , Volume 30 , Special Issue 2: Mild Behavioral Impairment , February 2018 , pp. 177 - 184
Copyright
Copyright © International Psychogeriatric Association 2017 

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References

American Psychiatric Association (2013). Diagnostic and Statistical Manual of Mental Disorders, 5th edn, Washington, DC: American Psychiatric Publishing.Google Scholar
Apostolova, L., Goukasian, N., Do, T., Grotts, J., Ringman, J. and Elashoff, D. (2016). Effect of brain amyloidosis on the emergence of neuropsychiatric behaviors in MCI over time. Neurology, 86, 232.Google Scholar
Baker, R. et al. (2001). A randomized controlled trial of the effects of multi-sensory stimulation (MSS) for people with dementia. British Journal of Clinical Psychology, 40, 81–96.CrossRefGoogle ScholarPubMed
Barcelos-Ferreira, R., Folquitto, J. C., Dos Santos Tascone, L. and Bottino, C. M. C. (2015). Mild behavioral impairment associated to higher prevalence of dementia in community-dwelling elderly subjects. Alzheimer's and Dementia, 11, 521.CrossRefGoogle Scholar
Cacciari, C. et al. (2010). White matter microstructure and apathy level in amnestic mild cognitive impairment. Journal of Alzheimer's Disease, 20, 501–507.CrossRefGoogle ScholarPubMed
Camargos, E. F. and Quintas, J. L. (2011). Apathy syndrome treated successfully with modafinil. BMJ Case Reports, 1–3.Google Scholar
Chan, W.-C. et al. (2010). Prevalence of neuropsychiatric symptoms in Chinese older persons with mild cognitive impairment-a population-based study. The American Journal of Geriatric Psychiatry, 18, 948–954.CrossRefGoogle ScholarPubMed
Choi, M. S. (2013). Neuropsychiatric symptoms in mild Alzheimer's disease and mild cognitive impairment. Journal of the Neurological Sciences, 333, 357.Google Scholar
Cummings, J. L., Mega, M., Gray, K., Rosenberg-Thompson, S., Carusi, D. A. and Gornbein, J. (1994). The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology, 44, 2308–2314.CrossRefGoogle ScholarPubMed
David, R. et al. (2008). Striatal dopamine transporter levels correlate with apathy in neurodegenerative diseases a SPECT study with partial volume effect correction. Clinical Neurology and Neurosurgery, 110, 19–24.Google Scholar
Delrieu, J. et al. (2014). Apathy as a feature of prodromal Alzheimer's disease: an FDG-PET ADNI study. International Journal of Geriatric Psychiatry, 30, 470–477.CrossRefGoogle ScholarPubMed
Di Iulio, F. et al. (2010). Occurrence of neuropsychiatric symptoms and psychiatric disorders in mild Alzheimer's disease and mild cognitive impairment subtypes. International Psychogeriatrics, 22, 629–640.Google Scholar
Drijgers, R. L., Aalten, P., Winogrodzka, A., Verhey, F. R. and Leentjens, A. F. (2009). Pharmacological treatment of apathy in neurodegenerative diseases: a systematic review. Dementia and Geriatric Cognitive Disorders, 28, 13–22.CrossRefGoogle ScholarPubMed
Feldman, H. H. et al. (2007). Effect of rivastigmine on delay to diagnosis of Alzheimer's disease from mild cognitive impairment: the InDDEx study. Lancet Neurology, 6, 501–512.Google Scholar
Fernandez-Martinez, M., Molano, A., Castro, J. and Zarranz, J. (2010). Prevalence of neuropsychiatric symptoms in mild cognitive impairment and Alzheimer's disease, and its relationship with cognitive impairment. Current Alzheimer Research, 7, 517–526.Google Scholar
Forrester, S. N., Gallo, J. J., Smith, G. S. and Leoutsakos, J. M. (2016). Patterns of neuropsychiatric symptoms in mild cognitive impairment and risk of dementia. American Journal of Geriatric Psychiatry, 24, 117–125.CrossRefGoogle ScholarPubMed
Freund-Levi, Y., Jedenius, E., Tysen-Backstrom, A. C., Larksater, M., Wahlund, L. O. and Eriksdotter, M. (2014). Galantamine versus risperidone treatment of neuropsychiatric symptoms in patients with probable dementia: an open randomized trial. American Journal of Geriatric Psychiatry, 22, 341–348.CrossRefGoogle ScholarPubMed
Geda, Y. E. et al. (2004). De novo genesis of neuropsychiatric symptoms in mild cognitive impairment (MCI). International Psychogeriatrics, 16, 51–60.Google Scholar
Geda, Y. E. et al. (2008). Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging: population-based study. Archives of General Psychiatry, 65, 1193–1198.Google Scholar
George, M., Whitfield, T. and Walker, Z. (2013). Association of apathy with frontal lobe dysfunction in amnestic mild cognitive impairment and alzheimer's disease. Journal of Neurology, Neurosurgery and Psychiatry, 84, 36.Google Scholar
Grambaite, R. et al. (2011). Executive dysfunction in mild cognitive impairment is associated with changes in frontal and cingulate white matter tracts. Journal of Alzheimer's Disease, 27, 453–462.CrossRefGoogle ScholarPubMed
Guercio, B. J. et al. (2015a). The apathy evaluation scale: a comparison of subject, informant, and clinician report in cognitively normal elderly and mild cognitive impairment. Journal of Alzheimer's Disease, 47, 421–432.CrossRefGoogle Scholar
Guercio, B. J. et al. (2015b). Apathy is associated with lower inferior temporal cortical thickness in mild cognitive impairment and normal elderly individuals. Journal of Neuropsychiatry and Clinical Neurosciences, 27, 22–27.CrossRefGoogle ScholarPubMed
Hwang, T. J., Masterman, D. L., Ortiz, F., Fairbanks, L. A. and Cummings, J. L. (2004). Mild cognitive impairment is associated with characteristic neuropsychiatric symptoms. Alzheimer Disease and Associated Disorders, 18, 17–21.Google Scholar
Ismail, Z. et al. (2016). Neuropsychiatric symptoms as early manifestations of emergent dementia: provisional diagnostic criteria for mild behavioral impairment. Alzheimer's and Dementia, 12, 195–202.Google Scholar
Ismail, Z. et al. (2017). The mild behavioral impairment checklist (MBI-C): a rating scale for neuropsychiatric symptoms in pre-dementia populations. Journal of Alzheimer's Disease, 56, 929–938.CrossRefGoogle ScholarPubMed
Jones, J. D., Mangal, P., Lafo, J., Okun, M. S. and Bowers, D. (2016). Mood differences among Parkinson's disease patients with mild cognitive impairment. Journal of Neuropsychiatry and Clinical Neurosciences, 28, 211–216.CrossRefGoogle ScholarPubMed
Kohler, C. A. et al. (2016). Neuropsychiatric disturbances in mild cognitive impairment (MCI): a systematic review of population-based studies. Current Alzheimer Research, 13, 1066–1082.CrossRefGoogle ScholarPubMed
Kuhlmei, A., Walther, B., Becker, T., Muller, U. and Nikolaus, T. (2013). Actigraphic daytime activity is reduced in patients with cognitive impairment and apathy. European Psychiatry: The Journal of the Association of European Psychiatrists, 28, 94–97.CrossRefGoogle ScholarPubMed
Lanctot, K. L. et al. (2014). Effect of methylphenidate on attention in apathetic AD patients in a randomized, placebo-controlled trial. International Psychogeriatrics, 26, 239–246.Google Scholar
Lyketsos, C. G., Steinberg, M., Tschanz, J. T., Norton, M. C., Steffens, D. C. and Breitner, J. C. (2000). Mental and behavioral disturbances in dementia: findings from the cache county study on memory in aging. American Journal of Psychiatry, 157, 708–714.CrossRefGoogle Scholar
Manera, V. et al. (2015). 'Kitchen and cooking,' a serious game for mild cognitive impairment and Alzheimer's disease: a pilot study. Frontiers in Aging Neuroscience, 7, 1–10.CrossRefGoogle ScholarPubMed
Manera, V. et al. (2016). A feasibility study with image-based rendered virtual reality in patients with mild cognitive impairment and dementia. PLoS One, 11, 1–14.CrossRefGoogle ScholarPubMed
Marin, R. S. (1990). Differential diagnosis and classification of apathy. American Journal of Psychiatry, 147, 22–30.Google Scholar
Marin, R. S., Biedrzycki, R. C. and Firinciogullari, S. (1991). Reliability and validity of the apathy evaluation scale. Psychiatry Research, 38, 143–162.CrossRefGoogle ScholarPubMed
Marshall, G. A. et al. (2013). Apathy is associated with increased amyloid burden in mild cognitive impairment. Journal of Neuropsychiatry and Clinical Neuroscience, 25, 302–307.CrossRefGoogle ScholarPubMed
Mega, M. S., Cummings, J. L., Fiorello, T. and Gornbein, J. (1996). The spectrum of behavioral changes in Alzheimer's disease. Neurology, 46, 130–135.CrossRefGoogle ScholarPubMed
Mehta, M. et al. (2008). Depressive symptoms in late life: associations with apathy, resilience and disability vary between young-old and old-old. International Journal of Geriatric Psychiatry, 23, 238–243.Google Scholar
Mulin, E. et al. (2011). Diagnostic criteria for apathy in clinical practice. International Journal of Geriatric Psychiatry, 26, 158–165.CrossRefGoogle ScholarPubMed
Munro, C. E. et al. (2015). Neuropsychiatric symptoms and functional connectivity in mild cognitive impairment. Journal of Alzheimer's Disease, 46, 727–735.CrossRefGoogle ScholarPubMed
Nakamura, K. et al. (2013). Apathy is more severe in vascular than amnestic mild cognitive impairment in a community: the Kurihara Project. Psychiatry & Clinical Neurosciences, 67, 517–525.Google Scholar
Onyike, C. U. et al. (2007). Epidemiology of apathy in older adults: the cache county study. American Journal of Geriatric Psychiatry, 15, 365–375.CrossRefGoogle ScholarPubMed
Palmer, K. et al. (2010). Neuropsychiatric predictors of progression from amnestic – mild cognitive impairment to alzheimer's disease: the role of depression and apathy. Journal of Alzheimer's Disease, 20, 175–183.Google Scholar
Panza, F. et al. (2005). Current epidemiology of mild cognitive impairment and other predementia syndromes. American Journal of Geriatric Psychiatry, 13, 633–644.CrossRefGoogle ScholarPubMed
Radakovic, R., Harley, C., Abrahams, S. and Starr, J. M. (2015). A systematic review of the validity and reliability of apathy scales in neurodegenerative conditions. International Psychogeriatrics, 27, 903–923.Google Scholar
Richard, E. et al. (2012). Symptoms of apathy are associated with progression from mild cognitive impairment to Alzheimer's disease in non-depressed subjects. Dementia and Geriatric Cognitive Disorders, 33, 204–209.Google Scholar
Robert, P. H. et al. (2006a). Neuropsychological performance in mild cognitive impairment with and without apathy. Dementia and Geriatric Cognitive Disorders, 21, 192–197.CrossRefGoogle ScholarPubMed
Robert, P. H. et al. (2006b). Apathy in patients with mild cognitive impairment and the risk of developing dementia of Alzheimer's disease. A one-year follow-up study. Clinical Neurology and Neurosurgery, 108, 733–736.CrossRefGoogle ScholarPubMed
Robert, P. et al. (2002). The apathy inventory: assessment of apathy and awareness in Alzheimer's disease, Parkinson's disease and mild cognitive impairment. International Journal of Geriatric Psychiatry, 17, 1099–1105.CrossRefGoogle ScholarPubMed
Robert, P. et al. (2009). Proposed diagnostic criteria for apathy in Alzheimer's disease and other neuropsychiatric disorders. European Psychiatry: The Journal of the Association of European Psychiatrists, 24, 98–104.Google Scholar
Rosenberg, P. B. et al. (2013). Safety and efficacy of methylphenidate for apathy in Alzheimer's disease: a randomized, placebo-controlled trial. Journal of Clinical Psychiatry, 74, 810–816.CrossRefGoogle ScholarPubMed
Sachs-Ericsson, N. and Blazer, D. G. (2015). The new DSM-5 diagnosis of mild neurocognitive disorder and its relation to research in mild cognitive impairment. Aging and Mental Health, 19, 2–12.CrossRefGoogle ScholarPubMed
Skogseth, R. et al. (2008). Neuropsychiatric correlates of cerebrospinal fluid biomarkers in Alzheimer's disease. Dementia and Geriatric Cognitive Disorders, 25, 559–563.CrossRefGoogle ScholarPubMed
Somme, J., Fernandez-Martinez, M., Molano, A. and Zarranz, J. J. (2013). Neuropsychiatric symptoms in amnestic mild cognitive impairment: increased risk and faster progression to dementia. Current Alzheimer Research, 10, 86–94.Google ScholarPubMed
Stanton, B. R. and Carson, A. (2016). Apathy: a practical guide for neurologists. Practical Neurology, 16, 42–47.Google Scholar
Stella, F., Radanovic, M., Aprahamian, I., Canineu, P. R., de Andrade, L. P. and Forlenza, O. V. (2014). Neurobiological correlates of apathy in Alzheimer's disease and mild cognitive impairment: a critical review. Journal of Alzheimer's Disease, 39, 633–648.CrossRefGoogle ScholarPubMed
Tam, C. W. et al. (2008). Clinical correlates of functional performance in community-dwelling Chinese older persons with mild cognitive impairment. International Psychogeriatrics, 20, 1059–1070.CrossRefGoogle ScholarPubMed
Taragano, F. E. et al. (2009). Mild behavioral impairment and risk of dementia: a prospective cohort study of 358 patients. Journal of Clinical Psychiatry, 70, 584–592.CrossRefGoogle ScholarPubMed
Verkaik, R., van Weert, J. C. and Francke, A. L. (2005). The effects of psychosocial methods on depressed, aggressive and apathetic behaviors of people with dementia: a systematic review. International Journal of Geriatric Psychiatry, 20, 301–314.Google Scholar
Vicini Chilovi, B., Conti, M., Zanetti, M., Mazzu, I., Rozzini, L. and Padovani, A. (2009). Differential impact of apathy and depression in the development of dementia in mild cognitive impairment patients. Dementia and Geriatric Cognitive Disorders, 27, 390–398.CrossRefGoogle ScholarPubMed
Volicer, L., Frijters, D. H. and van der Steen, J. T. (2013). Apathy and weight loss in nursing home residents: longitudinal study. Journal of the American Medical Directors Association, 14, 417–420.CrossRefGoogle ScholarPubMed
Zahodne, L. B. and Tremont, G. (2013). Unique effects of apathy and depression signs on cognition and function in amnestic mild cognitive impairment. International Journal of Geriatric Psychiatry, 28, 50–56.CrossRefGoogle ScholarPubMed