120| Apathy and Agitation in Neurodegenerative Diseases – A Conversation With Dr. Krista Lanctôt

This episode is a conversation with Dr. Krista Lanctôt about neuropsychiatric symptoms (NPS) in older adults with neurodegenerative diseases, with a focus on apathy and agitation. The discussion covers definitions, diagnostic criteria, epidemiology, methods of assessment, relation to degenerative neuropathology, and various treatment approaches.

A pdf of the transcript for this episode is available here.

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About Krista

Dr. Krista L. Lanctôt has a PhD in Clinical Pharmacology from the University of Toronto, with additional training in pharmacoepidemiology.  She is currently a Senior Scientist in Geriatric Psychiatry and in the Hurvitz Brain Sciences Program at Sunnybrook Research Institute, Research Co-Director in the Department of Psychiatry at Sunnybrook Health Sciences Centre and the Head of Neuropsychopharmacology Research.  In 2022, she was awarded the Bernick Chair is Geriatric Psychopharmacology. She is also a Professor of Psychiatry and Pharmacology/Toxicology, and Vice Chair of Basic and Clinical Sciences in the Department of Psychiatry at the University of Toronto, Toronto, Ontario, Canada.

Dr. Lanctôt is an active researcher with over 375 published papers, and Editor of the 2021 book “Apathy: Clinical and Neuroscientific Perspectives from Neurology and Psychiatry”.  Her group’s research has focused on optimizing the pharmacotherapy of cognition and neuropsychiatric symptoms associated with dementia and in predementia states.  She currently holds grants as a PI from the Alzheimer’s Drug Discovery Foundation, Alzheimer’s Association US, Weston Brain Institute and Canadian Institutes of Health Research.  She is a full member of the School of Graduate Studies in the Faculty of Medicine, University of Toronto, previous winner of the Faculty of Medicine Graduate Education Award, and has trained more than 40 graduate students.

Select Resources

Mild Behavioral Impairment Checklist (MBI-C)


Azhar, L., Kusumo, R. W., Marotta, G., Lanctôt, K. L., & Herrmann, N. (2022). Pharmacological management of apathy in dementia. CNS drugs, 36(2), 143-165.

Brodaty, H., & Burns, K. (2012). Nonpharmacological management of apathy in dementia: a systematic review. The American Journal of Geriatric Psychiatry, 20(7), 549-564.

Cai, Y., Li, L., Xu, C., & Wang, Z. (2020). The effectiveness of non‐pharmacological interventions on apathy in patients with dementia: a systematic review of systematic reviews. Worldviews on Evidence‐Based Nursing, 17(4), 311-318.

Chau, S. A., Chung, J., Herrmann, N., Eizenman, M., & Lanctôt, K. L. (2016). Apathy and attentional biases in Alzheimer’s disease. Journal of Alzheimer’s Disease, 51(3), 837-846.

Ferrero-Arias, J., Goñi-Imízcoz, M., Gonzalez-Bernal, J., Lara-Ortega, F., da Silva-González, Á., & Díez-Lopez, M. (2011). The efficacy of nonpharmacological treatment for dementia-related apathy. Alzheimer Disease & Associated Disorders, 25(3), 213-219.

Gitlin, L. N., Winter, L., Burke, J., Chernett, N., Dennis, M. P., & Hauck, W. W. (2008). Tailored activities to manage neuropsychiatric behaviors in persons with dementia and reduce caregiver burden: a randomized pilot study. The American Journal of Geriatric Psychiatry, 16(3), 229-239.

Goris, E. D., Ansel, K. N., & Schutte, D. L. (2016). Quantitative systematic review of the effects of non‐pharmacological interventions on reducing apathy in persons with dementia. Journal of advanced nursing, 72(11), 2612-2628.

Herrmann, N., Ruthirakuhan, M., Gallagher, D., Verhoeff, N. P. L., Kiss, A., Black, S. E., & Lanctôt, K. L. (2019). Randomized placebo-controlled trial of nabilone for agitation in Alzheimer’s disease. The American Journal of Geriatric Psychiatry, 27(11), 1161-1173.

Herrmann, N., Wang, H. J., Song, B. X., Bawa, K. K., & Lanctôt, K. L. (2022). Risks and benefits of current and novel drugs to treat agitation in Alzheimer’s disease. Expert Opinion on Drug Safety, 21(10), 1289-1301.

Ijaopo, E. O. (2017). Dementia-related agitation: a review of non-pharmacological interventions and analysis of risks and benefits of pharmacotherapy. Translational psychiatry, 7(10), e1250-e1250.

Ismail, Z., Agüera-Ortiz, L., Brodaty, H., Cieslak, A., Cummings, J., Fischer, C. E., … & Lyketsos, C. (2017). The Mild Behavioral Impairment Checklist (MBI-C): a rating scale for neuropsychiatric symptoms in pre-dementia populations. Journal of Alzheimer’s disease, 56(3), 929-938.

Kales, H. C., Gitlin, L. N., & Lyketsos, C. G. (2015). Assessment and management of behavioral and psychological symptoms of dementia. Bmj, 350.

Lanctôt, K. L., Agüera-Ortiz, L., Brodaty, H., Francis, P. T., Geda, Y. E., Ismail, Z., … & Abraham, E. H. (2017). Apathy associated with neurocognitive disorders: recent progress and future directions. Alzheimer’s & Dementia, 13(1), 84-100.

Lanctôt, K. L., Amatniek, J., Ancoli-Israel, S., Arnold, S. E., Ballard, C., Cohen-Mansfield, J., … & Boot, B. (2017). Neuropsychiatric signs and symptoms of Alzheimer’s disease: New treatment paradigms. Alzheimer’s & Dementia: Translational Research & Clinical Interventions, 3(3), 440-449.

Liu, C. S., Chau, S. A., Ruthirakuhan, M., Lanctôt, K. L., & Herrmann, N. (2015). Cannabinoids for the treatment of agitation and aggression in Alzheimer’s disease. CNS drugs, 29(8), 615-623.

Manera, V., Abrahams, S., Agüera-Ortiz, L., Bremond, F., David, R., Fairchild, K., … & Robert, P. (2020). Recommendations for the nonpharmacological treatment of apathy in brain disorders. The American Journal of Geriatric Psychiatry, 28(4), 410-420.

Miller, D. S., Robert, P., Ereshefsky, L., Adler, L., Bateman, D., Cummings, J., … & Lanctôt, K. L. (2021). Diagnostic criteria for apathy in neurocognitive disorders. Alzheimer’s & Dementia, 17(12), 1892-1904.

Mintzer, J., Lanctôt, K. L., Scherer, R. W., Rosenberg, P. B., Herrmann, N., Van Dyck, C. H., … & ADMET 2 Research Group. (2021). Effect of methylphenidate on apathy in patients with Alzheimer disease: the ADMET 2 randomized clinical trial. JAMA neurology, 78(11), 1324-1332.

Mohammad, D., Ellis, C., Rau, A., Rosenberg, P. B., Mintzer, J., Ruthirakuhan, M., … & Lanctôt, K. L. (2018). Psychometric properties of apathy scales in dementia: a systematic review. Journal of Alzheimer’s Disease, 66(3), 1065-1082.

Mortby, M. E., Adler, L., Agüera-Ortiz, L., Bateman, D. R., Brodaty, H., Cantillon, M., … & Theleritis, C. (2022). Apathy as a treatment target in Alzheimer’s disease: implications for clinical trials. The American Journal of Geriatric Psychiatry, 30(2), 119-147.

Raglio, A., Bellelli, G., Traficante, D., Gianotti, M., Ubezio, M. C., Villani, D., & Trabucchi, M. (2008). Efficacy of music therapy in the treatment of behavioral and psychiatric symptoms of dementia. Alzheimer Disease & Associated Disorders, 22(2), 158-162.

Robert, P., Lanctôt, K. L., Agüera-Ortiz, L., Aalten, P., Bremond, F., Defrancesco, M., … & Manera, V. (2018). Is it time to revise the diagnostic criteria for apathy in brain disorders? The 2018 international consensus group. European Psychiatry, 54, 71-76.

Ruthirakuhan, M. T., Herrmann, N., Abraham, E. H., Chan, S., & Lanctot, K. L. (2018). Pharmacological interventions for apathy in Alzheimer’s disease. Cochrane Database of Systematic Reviews, (5).

Ruthirakuhan, M., Herrmann, N., Andreazza, A. C., Verhoeff, N. P. L., Gallagher, D., Black, S. E., … & Lanctôt, K. L. (2020). Agitation, oxidative stress, and cytokines in Alzheimer disease: biomarker analyses from a clinical trial with nabilone for agitation. Journal of Geriatric Psychiatry and Neurology, 33(4), 175-184.

Ruthirakuhan, M. T., Herrmann, N., Gallagher, D., Andreazza, A. C., Kiss, A., Verhoeff, N. P. L., … & Lanctôt, K. L. (2019). Investigating the safety and efficacy of nabilone for the treatment of agitation in patients with moderate-to-severe Alzheimer’s disease: Study protocol for a cross-over randomized controlled trial. Contemporary clinical trials communications, 15, 100385.

Ruthirakuhan, M., Herrmann, N., Vieira, D., Gallagher, D., & Lanctôt, K. L. (2019). The roles of apathy and depression in predicting Alzheimer disease: a longitudinal analysis in older adults with mild cognitive impairment. The American Journal of Geriatric Psychiatry, 27(8), 873-882.

Ruthirakuhan, M., Lanctôt, K. L., Di Scipio, M., Ahmed, M., & Herrmann, N. (2018). Biomarkers of agitation and aggression in Alzheimer’s disease: a systematic review. Alzheimer’s & Dementia, 14(10), 1344-1376.

Scherer, R. W., Drye, L., Mintzer, J., Lanctôt, K., Rosenberg, P., Herrmann, N., … & van Dyck, C. H. (2018). The Apathy in Dementia Methylphenidate Trial 2 (ADMET 2): study protocol for a randomized controlled trial. Trials, 19(1), 1-15.

Sherman, C., Liu, C. S., Herrmann, N., & Lanctôt, K. L. (2018). Prevalence, neurobiology, and treatments for apathy in prodromal dementia. International Psychogeriatrics, 30(2), 177-184.

Sherman, C., Ruthirakuhan, M., Vieira, D., Lanctôt, K. L., & Herrmann, N. (2018). Cannabinoids for the treatment of neuropsychiatric symptoms, pain and weight loss in dementia. Current opinion in psychiatry, 31(2), 140-146.

Sung, H. C., & Chang, A. M. (2005). Use of preferred music to decrease agitated behaviours in older people with dementia: a review of the literature. Journal of clinical nursing, 14(9), 1133-1140.

Teselink, J., Bawa, K. K., Koo, G. K., Sankhe, K., Liu, C. S., Rapoport, M., … & Lanctôt, K. L. (2021). Efficacy of non-invasive brain stimulation on global cognition and neuropsychiatric symptoms in Alzheimer’s disease and mild cognitive impairment: A meta-analysis and systematic review. Ageing Research Reviews, 72, 101499.

Theleritis, C., Siarkos, K., Politis, A. A., Katirtzoglou, E., & Politis, A. (2018). A systematic review of non‐pharmacological treatments for apathy in dementia. International Journal of Geriatric Psychiatry, 33(2), e177-e192.

Tumati, S., Herrmann, N., Marotta, G., Li, A., & Lanctôt, K. L. (2022). Blood-based biomarkers of agitation in Alzheimer’s disease: Advances and future prospects. Neurochemistry International, 152, 105250.

van Dyck, C. H., Arnsten, A. F., Padala, P. R., Brawman-Mintzer, O., Lerner, A. J., Porsteinsson, A. P., … & Rosenberg, P. B. (2021). Neurobiologic rationale for treatment of apathy in Alzheimer’s disease with methylphenidate. The American Journal of Geriatric Psychiatry, 29(1), 51-62.

Watt, J. A., Goodarzi, Z., Veroniki, A. A., Nincic, V., Khan, P. A., Ghassemi, M., … & Straus, S. E. (2019). Comparative efficacy of interventions for aggressive and agitated behaviors in dementia: a systematic review and network meta-analysis. Annals of internal medicine, 171(9), 633-642.

Woods, D. L., Craven, R. F., & Whitney, J. (2005). The effect of therapeutic touch on behavioral symptoms of persons with dementia. Alternative Therapies in Health & Medicine, 11(1).

Zhao, Q. F., Tan, L., Wang, H. F., Jiang, T., Tan, M. S., Tan, L., … & Yu, J. T. (2016). The prevalence of neuropsychiatric symptoms in Alzheimer’s disease: systematic review and meta-analysis. Journal of affective disorders, 190, 264-271.