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CME / ABIM MOC / CE

Can Apathy in Mild Cognitive Impairment Predict Alzheimer’s Disease?

  • Authors: News Author: Batya Swift Yasgur, MA, LSW; CME Author: Laurie Barclay, MD
  • CME / ABIM MOC / CE Released: 4/28/2023
  • Valid for credit through: 4/28/2024, 11:59 PM EST
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  • Credits Available

    Physicians - maximum of 0.25 AMA PRA Category 1 Credit(s)™

    ABIM Diplomates - maximum of 0.25 ABIM MOC points

    Nurses - 0.25 ANCC Contact Hour(s) (0 contact hours are in the area of pharmacology)

    Physician Assistant - 0.25 AAPA hour(s) of Category I credit

    IPCE - 0.25 Interprofessional Continuing Education (IPCE) credit

    You Are Eligible For

    • Letter of Completion
    • ABIM MOC points

Target Audience and Goal Statement

This activity is intended for neurologists, family medicine/primary care clinicians, internists, psychiatrists, geriatricians, nurses, physician assistants, and other members of the health care team who treat and manage patients with mild cognitive impairment who may be at risk for progression to AD.

The goal of this activity is for learners to be better able to describe conversion rates from mild cognitive impairment to AD and the effect of apathy on this conversion.

Upon completion of this activity, participants will:

  • Assess conversion rates from mild cognitive impairment to AD and the effect of apathy on this conversion, based on the state-funded, longitudinal, multisite Texas Alzheimer’s Research and Care Consortium study
  • Evaluate clinical implications of conversion rates from mild cognitive impairment to AD and the effect of apathy on this conversion, based on the state-funded, longitudinal, multisite Texas Alzheimer’s Research and Care Consortium study
  • Outline implications for the healthcare team


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News Author

  • Batya Swift Yasgur, MA, LSW

    Freelance writer, Medscape

    Disclosures

    Batya Swift Yasgur, MA, LSW, has no relevant financial relationships.

CME Author

  • Laurie Barclay, MD

    Freelance writer and reviewer
    Medscape, LLC

    Disclosures

    Laurie Barclay, MD, has no relevant financial relationships.

Editor/Nurse Planner

  • Leigh Schmidt, MSN, RN, CNE, CHCP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Leigh Schmidt, MSN, RN, CNE, CHCP, has no relevant financial relationships.

Compliance Reviewer

  • Amanda Jett, PharmD, BCACP

    Associate Director, Accreditation and Compliance, Medscape, LLC

    Disclosures

    Amanda Jett, PharmD, BCACP, has no relevant financial relationships.

Peer Reviewer

This activity has been peer reviewed and the reviewer has no relevant financial relationships.


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CME / ABIM MOC / CE

Can Apathy in Mild Cognitive Impairment Predict Alzheimer’s Disease?

Authors: News Author: Batya Swift Yasgur, MA, LSW; CME Author: Laurie Barclay, MDFaculty and Disclosures

CME / ABIM MOC / CE Released: 4/28/2023

Valid for credit through: 4/28/2024, 11:59 PM EST

processing....

Clinical Context

Among adults with MCI, 35% to 85% have neuropsychiatric symptoms (NPS), which often occur in early AD and may precede measurable cognitive decline. Apathy is one of the most common NPS in patients with mild cognitive impairment (MCI), often co-occurring with depression and other NPS.

Apathy, defined as reduced self-initiated or environment-stimulated goal-directed behaviors with emotional flattening, affects approximately 11% to 45% of people with MCI. Patients with apathy are more likely to have functional impairment in activities of daily living, independent of age, cognitive function, and depression.

Study Synopsis and Perspective

The presence of apathy may predict conversion from MCI to Alzheimer’s disease (AD), new research suggests.

Investigators followed more than 1000 individuals with MCI over the course of an 8-year period. During that time, close to one fifth converted from MCI to AD. Of those with apathy, 36% developed AD versus 14% of those without apathy. Moreover, conversion to AD was more rapid in those with apathy versus those without a median of almost 4 years compared with a median of almost 7 years.

“The take-home message for clinicians is that apathy is associated with neurodegenerative diseases,” senior author Antonio Teixeira, MD, PhD, professor of psychiatry and head of the neuropsychiatry program, McGovern Medical School, UTHealth, Houston, Texas, told Medscape Medical News.

“If a person starts developing apathy it could either prompt further investigation or at least closer following,” he said.

The study was published online March 7 in the Journal of Alzheimers Disease.

Distinct Trajectories

Approximately 80% of patients with MCI go on to develop AD within a 6-year period, the investigators note. “Given the impact of AD, it is paramount to define parameters associated with distinct trajectories of MCI patients, especially identifying those who are more prone to develop AD.”

Dr Teixeira defined apathy as “loss of interest and reduction in goal-directed behaviors.”

NPS are reported in an estimated 35% to 85% of patients with MCI and also are often present in the early stages of AD, preceding the onset of measurable cognitive decline. Previous research suggests that NPS, including apathy, may predict conversion from MCI to dementia.

However, previous research “did not specifically evaluate the role of moderating factors,” such as age or MCI type. Moreover, previous studies have been conducted in primarily non-Hispanic White populations, “limiting the generalizability of the findings.”

The researchers therefore turned to subjects enrolled in the Texas Alzheimer’s Research and Care Consortium (TARCC)--a cohort with a significant percentage of Hispanic participants--to explore conversion rates for MCI to AD and determine the predictive role of apathy in the progression from MCI to AD.

TARCC is a state-funded longitudinal multisite study consisting of a cohort of adults 50 years old or older who are noncognitively impaired, patients with MCI, and patients with AD.

Family members/caregivers completed the Neuropsychiatry Inventory Questionnaire (NPI-Q), and participants underwent a battery of cognitive tests, including the Mini-Mental State Exam (MMSE).

The study included 1092 individuals diagnosed with MCI at any point during the study (59% women; mean [SD] age, 71.8 [standard deviation, 8.61] years; mean years of education, 12.58 [standard deviation, 4.38]). The cohort was evenly divided between Hispanic and non-Hispanic participants.

Of the total cohort, 158 individuals had apathy and 934 did not.

Researchers performed a total of 2897 observations, with the number of observations ranging from 1 to 9 per individual and a median observation count per participant of 2 (interquartile range: 1, 4).

Participants were followed for 8.2 years.

Efficient and Scalable

During the study period, 17.3% of participants experienced conversion from MCI to AD across all observations, with a median time to conversion of 6.4 years.

Researchers stratified the severity of apathy using a 4-level index, beginning with “no apathy” and going through “mild,” moderate,” and “severe” apathy. The presence of apathy was significantly related to the outcome, with the relationship increasing in tandem with greater severity (Table 1).

Table 1. Apathy Severity and Relationship to Outcome

Apathy Severity

Relationship to Outcome, Hazard Ratio

P value

Mild

2.10

<.001

Moderate

2.31

<.001

Severe

2.51

.048

Moderation models found that age had a significant moderating effect (adjusted P=.002). For those who had apathy, the relationship between age and time to conversion was “essentially null.” However, for those without apathy, there was a 5% increase in the hazard of conversion per additional year of age (P<.001).

In adjusted and unadjusted models, MMSE score showed a moderating effect (P<.001), but the effect was stronger in those with versus without apathy (hazard ratio, 0.75 vs 0.87, respectively; both P<.001).

“Our results showed that MCI patients with apathy have significantly higher conversion rates to AD compared with MCI patients without apathy, even after adjustment for confounding factors,” the investigators write.

Dr Teixeira noted that there is “overlap” between depression and apathy, but not all people with depression experience apathy, and all apathy is not necessarily related to depression, “which is why we controlled for depression.”

He observed that many clinicians treat patients with apathy by prescribing antidepressants. “But the apathy may not necessarily be associated with depression, and antidepressants might even make it worse. It’s important to tease out apathy from depression,” he said.

Assessing apathy may be an “efficient and highly scalable method for improving risk stratification across clinical and research settings,” the researchers note.

One of Many Factors

Commenting on the study for Medscape Medical News, Claire Sexton, DPhil, senior director of scientific programs and outreach, Alzheimer’s Association, said: ”A strength of this research is that the study population is significantly more diverse than previous work on this topic.”

However, “the study also has a number of limitations, including short follow-up time and diagnosis that did not include measurement of key biomarkers; therefore, for these findings to have a high level of credibility they need to be replicated in more rigorous studies,” said Dr Sexton, who was not involved with the study.

“Based on the totality of research, it is still very likely that apathy is only one of many factors that influence the rate of progression from MCI to Alzheimer’s dementia,” she added.

She noted that the Alzheimer’s Association “believes that it is important for clinicians--and family caregivers--to monitor for and manage behavioral and neuropsychiatric symptoms, including apathy, throughout the disease course,” which “can be an important part of maintaining or improving everyone’s quality of life.”

This study was supported by the Texas Alzheimer’s Research and Care Consortium. Dr Teixeira, other study authors, and Dr Sexton have reported no relevant financial relationships.

J Alzheimers Dis. Published online March 7, 2023.[1]

Study Highlights

  • Family members/caregivers assessed apathy by a positive response on the corresponding NPI-Q item.
  • The final TARCC data set included 2897 observations from 1092 individuals with baseline MCI.
  • Mean age was 71.8±8.6; 59% were women; Hispanics and non-Hispanics were equally represented.
  • Probabilities of conversion to AD over time across all individuals and between those with and without apathy were estimated with Kaplan-Meier survival curves.
  • During follow-up (8.21 years), 190 individuals (17.3%) converted from MCI to AD across observations (median time to conversion, 6.41 years).
  • Conversion to AD occurred in 158 individuals with apathy (36.1%) versus 934 without apathy (14.2%).
  • Median time to conversion was 3.79 and 6.83 years, respectively.
  • Cox proportional hazards regression found significant effects of several predictors, including apathy, on time to conversion.
  • In univariate analysis, predictors significantly related to conversion were male sex (hazard ratio [HR], 1.50), older age (HR, 1.04; 4% increase for each additional year), amnestic type MCI (HR, 1.63), depression (HR, 1.63), lower MMSE scores (HR, 0.88 for higher score; 12% lower for each additional point), and non-Hispanic ethnicity (HR, 0.35 for Hispanic ethnicity; P<.05).
  • In the full multiple predictor model, depression was not significant when adjusting for age, MMSE score, sex, ethnicity, MCI type, and apathy.
  • Individuals with vs without apathy had 2.4-fold greater hazard of conversion.
  • The relationship of apathy to conversion strengthened as severity increased (mild: HR, 2.10 [P<.001]; moderate: HR, 2.31 [P<.001]; severe: HR, 2.51 [P=.048]).
  • Age had a significant moderating effect (adjusted P=.002), with essentially no effect on time to conversion among participants with apathy, but with 5% increase in hazard of conversion per additional year of age (P<.001) among those without apathy.
  • In adjusted and unadjusted models, MMSE score had a moderating effect (P<.001) that was stronger in those with versus without apathy (HR, 0.75 vs 0.87; both P<.001).
  • The final multiple predictor model found that estimates were largely stable after removing depression.
  • The investigators concluded that NPS, particularly apathy, are associated with MCI to AD progression, even after adjustment for confounders, suggesting that apathy assessment might improve risk prediction and targeted intervention.
  • The findings corroborate previous studies regarding apathy predicting MCI to AD conversion and confirm generalizability to a diverse population, including a significant percentage of Hispanics.
  • Unlike established clinical assessments such as amyloid and tau PET imaging, apathy evaluation is cost-effective and noninvasive and does not require expensive equipment.
  • Apathy assessments may therefore offer an efficient, highly scalable tool to improve risk stratification across clinical and research settings.
  • Despite some overlap between depression and apathy, it is important to differentiate these, as antidepressants may worsen apathy in patients who are not depressed.
  • As apathy may be one of many factors affecting progression from MCI to AD, clinicians and caregivers should monitor and manage apathy and other NPS throughout the disease course, to help maintain or improve quality of life.
  • Apathy also seems to predict worse cognitive and functional outcomes in Parkinson’s disease, stroke, and other conditions.
  • Given that age and cognitive performance moderated the association between apathy and MCI-AD conversion, apathy may be a behavioral expression of the underlying pathophysiological process, and not necessarily a mechanism underlying the conversion.
  • Study limitations include short follow-up and diagnosis without key biomarkers, warranting further, more rigorous studies to confirm the findings.

Clinical Implications

  • NPS, particularly apathy, are associated with MCI to AD progression.
  • Apathy assessment might improve risk prediction and targeted intervention delivery.
  • Implications for the Health Care Team: Clinicians and caregivers should monitor apathy throughout the disease course, to help maintain quality of life.

 

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