Also In This Special Report
Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP
Brandon C. Yarns, MD, MS; and Aubrey M. Freitas
Mario Fahed, MD
Dax Volle, MD; and Brian Rosen, MD
Nina Vadiei, PharmD; Jinjiao Wang, PhD, RN; and Samantha Catanzano, PharmD
Apathy significantly affects cognitive impairment patients, yet remains underrecognized. Discover effective assessment and treatment strategies for improved outcomes.
SPECIAL REPORT: GERIATRIC PSYCHIATRY
Apathy, defined as a quantitative reduction in goal-directed activity compared with a patient’s previous functioning, is highly prevalent and pervasive in patients with cognitive impairment. It significantly impacts treatment outcomes across psychiatric and neurological conditions.1 Despite its prevalence and clinical significance, apathy as a syndrome remains underrecognized and undertreated in general psychiatric practice.2 Recent advances in assessment tools, treatment approaches, and our understanding of apathy subtypes now provide evidence-based strategies for effective management.
The 2021 consensus criteria define apathy as persistent symptoms (≥ 4 weeks) affecting at least 2 of the following domains: diminished initiative, diminished interest, or diminished emotional expression/responsiveness.3 Unlike depression, apathy involves emotional blunting and indifference rather than persistent negative mood states (Table 1).4
Case Vignette 1: Late-Life Depression vs Apathy
“Gemma,” a retired teacher aged 73 years, presents with her daughter’s concerns about “giving up on everything” during the past 3 months. Gemma has stopped gardening, no longer calls her friends, and shows little interest in her grandchildren’s visits. She denies feeling sad, hopeless, or guilty, stating, “I just don’t see the point anymore.” She does not show any somatic preoccupation. Her daughter notes Gemma responds to direct requests but rarely initiates activities independently.
Rajesh R. Tampi, MD, MS, DFAPA, DFAAGP
Brandon C. Yarns, MD, MS; and Aubrey M. Freitas
Mario Fahed, MD
Dax Volle, MD; and Brian Rosen, MD
Nina Vadiei, PharmD; Jinjiao Wang, PhD, RN; and Samantha Catanzano, PharmD
This presentation illustrates the distinction between apathy and depression, which often co-occur with neurocognitive disorders.4 Although both conditions involve reduced activity and interest, apathy is characterized by emotional neutrality rather than negative affect.2 Gemma’s lack of dysphoria, guilt, or hopelessness, as well as somatic preoccupation combined with her responsiveness to external stimuli, suggests primary apathy rather than depression.
The 3 Subtypes of Apathy
Research has identified 3 neurobiologically distinct apathy subtypes, each requiring different therapeutic approaches5:
1. Executive apathy (cognitive).
2. Emotional apathy (affective).
3. Initiation apathy (auto-activation).
The Patient and Caregiver Experience
Recent qualitative research by Burgon et al reveals that patients and caregivers did not recognize apathy as a manifestation of neurocognitive decline but rather as an understandable response to everyday struggles with cognitive and physical decline.6 Clinicians can reframe apathy for families as a neurobiological symptom rather than a behavioral choice. This reduces caregiver distress and guilt while promoting therapeutic engagement.
Key themes from patient and caregiver interviews include the following6:
Assessment Algorithm
To best assess for apathy, screen all patients 65 years or older with the Brief Dimensional Apathy Scale (b-DAS) as part of routine visits or the comprehensive Apathy Motivation Index (AMI) assessment (Table 2). Clinicians can then identify predominant subtype(s) for targeted intervention and evaluate environmental and social contextual factors.6 It is also important to rule out depression, cognitive impairment, and potential medication effects during assessment. Lastly, it is imperative to support any potential caregiver burnout. The following tools can be used during this process.
For quick screening (2-3 minutes)…
b-DAS7: There are 9 items assessing all 3 subtypes with a clinical cutoff for significant apathy for each.
For comprehensive assessment (10-15 minutes)…
AMI8: There are 18 items with excellent psychometric properties.
Assessment should tackle not just symptom severity but also environmental factors and caregiver dynamics that influence the presentation of apathy. Consider and document social support availability, environmental considerations, impediments to engagement, caregiver understanding, and cultural factors (as expression of motivation varies across cultural backgrounds) in your assessment.6
Etiology-Specific Interventions
Alzheimer Disease
Initiate donepezil or galantamine if the patient is not already receiving it for Alzheimer dementia.9 Add-on methylphenidate. The landmark ADMET 2 trial established methylphenidate 20 mg daily as the first evidence-based treatment for apathy in Alzheimer disease. Over 6 months, 27% of treated participants achieved complete remission vs 14% with placebo.10
Dosing Strategy:
Parkinson Disease
Dopamine agonists are the preferred first-line treatment. Network meta-analysis demonstrates efficacy of dopaminergic agonists but found them to be comparable in efficacy to other medication classes (cholinesterase inhibitors and antidepressants).11 Dopaminergic medications are especially helpful for apathy in early Parkinson disease.12
Treatment Hierarchy Based on Quality of Evidence9:
Late-Life Depression
Address selective serotonin reuptake inhibitor (SSRI)–induced apathy. Ranges of 20% to 92% of patients on SSRIs develop treatment-emergent apathy.13 Recent evidence supports switching strategies rather than augmentation.
Management Algorithm:
Case Vignette 2: Alzheimer Disease With Apathy
“Robert,” a man aged 78 years, has mild Alzheimer disease, which was diagnosed approximately 18 months ago. His wife now reports that he has stopped his woodworking hobby, rarely speaks during family dinners, and needs prompting for basic hygiene. Donepezil has helped his memory but has not addressed the motivational decline. Mini-Mental State Exam: 24/30; AMI score: 2.1 (predominantly initiation apathy).
After 8 weeks of treatment with methylphenidate 5 mg twice a day, titrated to 10 mg twice daily over 2 weeks, Robert resumed simple woodworking projects and was more conversational at follow-up. His wife noted he now initiates some daily activities independently sometimes.
Pharmacological Interventions
Based on the 3 subtypes of apathy mechanisms4,9:
Cognitive Processing Deficits (Dorsolateral PFC-Caudate):
Emotional-Affective Processing Deficits (Orbital-medial PFC):
Auto-Activation Deficits (Basal Ganglia Output):
Nonpharmacological Interventions
Executive Apathy
Several behavioral activation interventions can be used to target executive apathy, including structured and predictable activity scheduling with graded task assignment, breaking complex activities into manageable steps, using external prompts and reminders, and focusing on previously enjoyed activities with high potential for reward.
Emotional Apathy
Interventions for emotional apathy can focus on social engagement. This can include group activities that target interpersonal connection. Music therapy has shown evidence in Parkinson disease,14 whereas virtual reality environments have shown promise in socially isolated patients.15
Environmental Modification for Initiation Apathy
Patients with initiation apathy may respond best to environmental modifications. Whenever possible, clinicians should help patients reduce decision-making demands, help provide or plan clear daily structure and routines, use visual cues and prompts, and train caregivers in prompting techniques.
Future Directions
Both repetitive transcranial magnetic stimulation (rTMS) and digital monitoring have shown promise in addressing apathy. High-frequency rTMS protocols targeting dorsolateral prefrontal cortex show efficacy in Alzheimer disease,16 and wearable devices may present an opportunity to screen for apathy through activity patterns, potentially enabling early detection and treatment response monitoring.
Concluding Thoughts
Apathy is a pervasive and treatment-resistant syndrome requiring systematic assessment and targeted intervention. By using validated screening tools for routine apathy detection, understanding apathy subtypes, and applying condition-specific, evidence-based pharmacological and behavioral treatment algorithms, psychiatrists can improve the quality of life of patients and their families.
Dr Fahed is an associate professor of psychiatry at the University of Connecticut School of Medicine in Farmington and an adjunct faculty member at the Yale School of Medicine in New Haven, Connecticut. He is board certified in geriatric psychiatry and adult psychiatry.
References
1. Robert P, Lanctôt KL, Agüera-Ortiz L, et al.
2. Steffens DC, Fahed M, Manning KJ, Wang L.
3. Miller DS, Robert P, Ereshefsky L, et al.
4. Lanctôt KL, Ismail Z, Bawa KK, et al.
5. Levy R, Dubois B.
6. Burgon C, Goldberg S, van der Wardt V, Harwood RH.
7. Radakovic R, McGrory S, Chandran S, et al.
8. Ang YS, Lockwood P, Apps MAJ, et al.
9. Theleritis C, Siarkos K, Politis A, et al.
10. Mintzer J, Lanctôt KL, Scherer RW, et al; ADMET 2 Research Group.
11. Mai AS, Lee YS, Yong JH, et al.
12. Castrioto A, Schmitt E, Anheim M, et al.
13. Masdrakis VG, Markianos M, Baldwin DS.
14. Shah-Zamora D, Anderson S, Barton B, Fleisher JE.
15. Ho KY, Cheung PM, Cheng TW, et al.
16. Jin Y, Li J, Xiao B.
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