Self- versus caregiver-reported apathy across neurological disorders

Abstract

Apathy is a prevalent and persistent neuropsychiatric syndrome across many neurological disorders, significantly impacting both patients and caregivers. We systematically quantified discrepancies between self- and caregiver-reported apathy in 335 patients with a variety of diagnoses, such as frontotemporal dementia (behavioural variant and semantic dementia subtypes), Parkinson's disease, Parkinson's disease dementia, dementia with Lewy bodies, Alzheimer's disease dementia, mild cognitive impairment, small vessel cerebrovascular disease, subjective cognitive decline and autoimmune encephalitis. Using the Apathy Motivation Index (AMI) and its analogous caregiver version (AMI-CG), we found that caregiver-reported apathy consistently exceeded self-reported levels across all conditions. Moreover, self-reported apathy accounted for only 14.1% of the variance in caregiver ratings. This apathy reporting discrepancy was most pronounced in conditions associated with impaired insight, such as behavioural variant frontotemporal dementia, and was significantly correlated with cognitive impairment. Deficits in memory and fluency explained an additional 11.2% of the variance in caregiver-reported apathy. Specifically, executive function deficits (e.g. indexed by fluency) and memory impairments may contribute to behavioural inertia or recall of it. These findings highlight the need to integrate patient and caregiver perspectives in apathy assessments, especially for conditions with prominent cognitive impairment. To improve diagnostic accuracy and deepen our understanding of apathy across neurological disorders, we highlight the need for adapted apathy assessment strategies that account for cognitive impairment particularly in individuals with insight or memory deficits. Understanding the cognitive mechanisms underpinning discordant apathy reporting in dementia might help inform targeted clinical interventions and reduce caregiver burden.

Keywords: cognitive impairment; dementia; impaired insight; informant report; rating discrepancy.

Graphical Abstract

Figure 1

Prevalence of self-reported apathy, depression, and anhedonia. (A) Venn diagram illustrating the overlap between self-reported apathy, depression and anhedonia in all patients (N = 292). Yellow, pink and blue circles represent apathy, anhedonia and depression, respectively. See the ‘Methods’ section for cut-off criteria. The SD group is excluded due to insufficient data (n = 1). Details of prevalence are in Supplementary Table 2. (B–J) Venn diagrams illustrating the overlap between self-reported apathy, depression and anhedonia within each diagnostic group: (B) bvFTD (N = 22), (C) SVD (N = 24), (D) AIE (N = 52), (E) PD (N = 57), (F) PDD (N = 17), (G) DLB (N = 17), (H) AD (N = 53), (I) MCI (N = 7) and (J) SCD (N = 42).

Figure 2

Discrepancy in apathy determined by caregiver report and self-report. Venn diagrams illustrating the discrepancy between caregiver- and self-reported apathy, using an AMI cut-off of 1.91 for both. Orange circles show apathy determined by caregiver report; yellow circles show apathy determined by self-report. (A) All patients (N = 335). (B–J) Discrepancy within each diagnostic group: (B) bvFTD (N = 43, (C) SVD (N = 24), (D) AIE (N = 53), (E) PD (N = 58), (F) PDD (N = 19), (G) DLB (N = 18), (H) AD (N = 54), (I) MCI (N = 7) and (J) SCD (N = 43). In the SD group (not shown), no individuals were classified as apathetic via self-report, whereas 6 of 16 individuals were classified as apathetic via caregiver report.

Figure 3

Factor structures for AMI caregiver and AMI self-report (N = 335). (Left) Results of the EFA for the 18-item AMI reported by patients themselves are shown for the three factors. The item label shows the original question used in the AMI-SR. The order of items is arbitrary. Pink bars indicate positive loadings, and green bars indicate negative loadings. Factors 1, 2 and 3 primarily load on questions from the three apathy subdomains of the AMI: behavioural apathy, social apathy and emotional apathy. The Kaiser–Meyer–Olkin measure was 0.85, confirming the sampling adequacy for factor analysis. Horn’s parallel analysis further supported the retention of three factors. EFA yielded a three-factor model that adequately fit the data [χ²(102) = 152.5, P < 0.001], explaining 37.5% of the variance. The model demonstrated good fit indices (RMSEA = 0.039, 90% CI 0.025–0.051; SRMR = 0.036; TLI = 0.94; CFI = 0.96; BIC = −439.3). This is consistent with the AMI-SR data from the prior studies in healthy population. (Right) The caregiver’s reports also assessed the same three apathy subdomains, but with a different factor order: behavioural apathy, emotional apathy and social apathy. The Kaiser–Meyer–Olkin measure was 0.90, confirming the sampling adequacy for factor analysis. Horn's parallel analysis further supported the retention of three factors. EFA yielded a three-factor model that adequately fit the data [χ²(102) = 229.4, P < 0.001], explaining 50.5% of the variance. The model demonstrated good fit indices (RMSEA = 0.062, 90% CI 0.051–0.072; SRMR = 0.035; TLI = 0.93; CFI = 0.95; BIC = −361.8). This structure, including the factor order, is consistent with the AMI-CG data from the prior study. Both exploratory factor analyses used parallel analysis to decide the number of factors. The factors appear non-orthogonal because Promax rotation was applied, allowing for inter-factor correlations. This choice was based on prior evidence that the subdomains of apathy are interrelated.

Figure 4

Correlation matrix for AMI-CG and self-report measures. Correlation matrix for AMI-CG total and subscale scores with self-reported AMI, GDS and SHAPS scores, along with ACE total score (cognitive function) for all patients (N = 335). The pink box highlights the crucial CG-SR discrepancy for AMI total score as well as the three subscales. Values in the cells and background colour indicate Spearman’s ρ correlation coefficients. Correlations that did not survive correction for multiple comparisons are left blank. Bonferroni correction was applied for multiple comparison correction with α = 0.00045, computed based on 0.05/total number of correlations computed.

Figure 5

Correlation between self-reported and caregiver-reported apathy across patient groups. AMI-CG scores show moderate to strong correlations with their corresponding self-report scores in some, but not all, groups. (A) AMI total score, (B) AMI behavioural subscale, (C) AMI social subscale and (D) AMI emotional subscale. Coloured lines indicate each cohort. Spearman’s ρ and P-values are shown.

Figure 6

Prevalence of apathy based on patient and caregiver reports. The prevalence of apathy in different severity level is stacked as 100% for each group. (A) Apathy prevalence based on patient-reported AMI. (B) Apathy prevalence based on caregiver-reported AMI. The green portion of the bar represents no apathy (AMI total < 1.91), orange indicates moderate apathy (AMI total score ≥ 1.91) and purple indicates severe apathy (AMI total score ≥ 2.38). Sample sizes for each subgroup: bvFTD = 43, SD = 16, SVD = 24, AIE = 53, PD = 58, PDD = 19, DLB = 18, Ad = 54, MCI = 7, SCD = 43 and HCs = 19. See Supplementary Table 4 for the breakdown for each of three apathy subdomains.

Figure 7

Caregiver-reported apathy and cognitive impairment. (A) Mean ACE total score for each cohort. The red horizontal dashed line indicates the cut-off for normal (88/100) ACE total score. Error bar indicates 1 SEM. (B) Mean AMI total score for each cohort rated by patients themselves (grey bars) and their caregivers (orange bars). Results of paired t-tests comparing self- and caregiver-reported AMI total scores are shown above the paired bars for each cohort. Bonferroni correction has been applied for multiple comparisons. (C) The ARD for AMI total, behavioural, social and emotional subscore. In all plots, error bars indicate 1 SEM. Results of one-sample t-test against 0 is shown at the bottom of each bar. Bonferroni correction has been applied for multiple comparisons. *P < 0.05, **P < 0.01, ***P < 0.001. ns, not significant. P-values were unadjusted. Sample sizes for each subgroup: bvFTD = 43, SD = 16, SVD = 24, AIE = 53, PD = 58, PDD = 19, DLB = 18, Ad = 54, MCI = 7, SCD = 43 and HCs = 19.

Figure 8

Correlation between ARD and cognitive measures. (A) Correlation matrix displaying the relationships between ARD, cognitive measures, depression, anhedonia and demographic variables across all patients (N = 314). Values in the cells and background colour indicate Spearman’s ρ correlation coefficients. Correlations that did not survive correction for multiple comparisons are left blank. Bonferroni correction was applied for multiple comparison correction with α = 0.001, computed based on 0.05/total number of correlations computed. (B) Correlation between ARD total and ACE total (i.e. the top left corner in A) across patient groups. Coloured lines indicate each cohort. Spearman’s ρ and P-values are shown.