Neuropsychiatric symptoms and global functional impairment along the Alzheimer's continuum

Abstract

Background/aims: Neuropsychiatric symptoms in Alzheimer's disease (AD) are highly prevalent. We sought to determine whether neuropsychiatric symptoms were related to global functional impairment at baseline and over a 3-year period in older normal control (NC), mild cognitive impairment (MCI) and mild AD dementia subjects.

Methods: Eight hundred and twelve subjects (229 NC, 395 MCI, 188 AD) from the Alzheimer's Disease Neuroimaging Initiative study underwent cognitive and behavioral assessments over 3 years.

Results: Greater hallucinations, anxiety and apathy were associated with greater global functional impairment at baseline, while the presence of hallucinations and apathy at baseline was associated with greater global functional impairment over time across all subjects. The following neuropsychiatric symptoms were not significantly associated with global functioning: delusions, agitation, depression, euphoria, disinhibition, irritability, aberrant motor behaviors, sleep and appetite.

Conclusions: These results suggest that increased baseline hallucinations, apathy and anxiety are associated with current and future disease progression in AD.

Figure 1

Scatter plots of CDR-SB, representing global functional impairment, vs. NPI-Q Hallucinations (A), Anxiety (B), and Apathy severity (C) in NC, MCI, and AD dementia subjects. Spearman’s rank correlation coefficients (r_s) and corresponding p values are provided for each diagnostic group. AD (Alzheimer’s disease), CDR-SB (Clinical Dementia Rating sum of boxes), MCI (mild cognitive impairment), NC (normal older control), NPI-Q (Neuropsychiatric Inventory Questionnaire brief form).

Figure 1

Scatter plots of CDR-SB, representing global functional impairment, vs. NPI-Q Hallucinations (A), Anxiety (B), and Apathy severity (C) in NC, MCI, and AD dementia subjects. Spearman’s rank correlation coefficients (r_s) and corresponding p values are provided for each diagnostic group. AD (Alzheimer’s disease), CDR-SB (Clinical Dementia Rating sum of boxes), MCI (mild cognitive impairment), NC (normal older control), NPI-Q (Neuropsychiatric Inventory Questionnaire brief form).

Figure 1

Scatter plots of CDR-SB, representing global functional impairment, vs. NPI-Q Hallucinations (A), Anxiety (B), and Apathy severity (C) in NC, MCI, and AD dementia subjects. Spearman’s rank correlation coefficients (r_s) and corresponding p values are provided for each diagnostic group. AD (Alzheimer’s disease), CDR-SB (Clinical Dementia Rating sum of boxes), MCI (mild cognitive impairment), NC (normal older control), NPI-Q (Neuropsychiatric Inventory Questionnaire brief form).

Figure 2

Values predicted from general linear model of CDR-SB regressed on diagnostic group and NPI-Q Hallucinations (A), Anxiety (B), and Apathy severity (C). The lines indicate the predicted values for CDR-SB, and the symbols denote corresponding actual values (overlapping observations at the same coordinates are sometimes hidden). The final model included a number of additional partialed significant predictors, but to simplify the visual display, they were not included in the model producing the predicted values in the figures (including them had a negligible effect on the relations seen). AD (Alzheimer’s disease), CDR-SB (Clinical Dementia Rating sum of boxes), MCI (mild cognitive impairment), NC (normal older control), NPI-Q (Neuropsychiatric Inventory Questionnaire brief form).

Figure 2

Values predicted from general linear model of CDR-SB regressed on diagnostic group and NPI-Q Hallucinations (A), Anxiety (B), and Apathy severity (C). The lines indicate the predicted values for CDR-SB, and the symbols denote corresponding actual values (overlapping observations at the same coordinates are sometimes hidden). The final model included a number of additional partialed significant predictors, but to simplify the visual display, they were not included in the model producing the predicted values in the figures (including them had a negligible effect on the relations seen). AD (Alzheimer’s disease), CDR-SB (Clinical Dementia Rating sum of boxes), MCI (mild cognitive impairment), NC (normal older control), NPI-Q (Neuropsychiatric Inventory Questionnaire brief form).

Figure 2

Values predicted from general linear model of CDR-SB regressed on diagnostic group and NPI-Q Hallucinations (A), Anxiety (B), and Apathy severity (C). The lines indicate the predicted values for CDR-SB, and the symbols denote corresponding actual values (overlapping observations at the same coordinates are sometimes hidden). The final model included a number of additional partialed significant predictors, but to simplify the visual display, they were not included in the model producing the predicted values in the figures (including them had a negligible effect on the relations seen). AD (Alzheimer’s disease), CDR-SB (Clinical Dementia Rating sum of boxes), MCI (mild cognitive impairment), NC (normal older control), NPI-Q (Neuropsychiatric Inventory Questionnaire brief form).

Figure 3

Predicted values from fixed effects of best fitting longitudinal model of CDR-SB by NPI-Q Hallucinations and selected baselines by diagnostic groups: NC (Top), MCI (Middle), and AD dementia (Bottom). Age, NPI-Q Apathy, RAVLT Total Learning, and Digit Symbol at baseline set equal to grand means. AD (Alzheimer’s disease), CDR-SB (Clinical Dementia Rating sum of boxes), MCI (mild cognitive impairment), NC (normal older control), NPI-Q(Neuropsychiatric Inventory Questionnaire brief form), RAVLT (Rey Auditory Verbal Learning Test).

Figure 4

Predicted values from fixed effects of best fitting longitudinal model of CDR-SB by NPI-Q Apathy and selected baselines by diagnostic groups: NC (Top), MCI (Middle), and AD dementia (Bottom). Age, NPI-Q Hallucinations, RAVLT Total Learning, and Digit Symbol at baseline set equal to grand means. AD (Alzheimer’s disease), CDR-SB (Clinical Dementia Rating sum of boxes), MCI (mild cognitive impairment), NC (normal older control), NPI-Q (Neuropsychiatric Inventory Questionnaire brief form), RAVLT (Rey Auditory Verbal Learning Test).

Figure 5

Kaplan-Meier survival curves of progression from MCI to AD dementia as predicted by NPI-Q Anxiety, where “survival” = has not progressed from MCI to AD dementia as of yet. Predicted values displayed are estimated holding other significant covariates in the model (Baseline RAVLT Total Learning, Baseline Digit Symbol, APOE4 Status, and Sex) constant at their respective grand means, and setting Sex = Female. Shading indicates 95% confidence limits. AD (Alzheimer’s disease), MCI (mild cognitive impairment), NPI-Q (Neuropsychiatric Inventory Questionnaire brief form), RAVLT (Rey Auditory Verbal Learning Test).