Two hundred seventy volunteers, 160 men (59.3%) and 110 women (40.7%) were evaluated at baseline and diagnosed as cognitively intact (n = 103, 38.2%), cognitively impaired (n = 74, 27.4%), or as having dementia (n = 93, 34.4%). One hundred and twelve subjects (41.5%) were determined to have lacunes. The majority of subjects (n = 214, 79.3%) were Caucasian, and the mean age of the sample was 74.6 years (range 52–94 years). describes the demographic and clinical characteristics of the sample.
In the entire sample, 49 subjects (18.1%) were rated with clinically significant depressed mood, 34 (12.7%) were rated to have anhedonia, 71 (26.3%) had anergia, and 49 (18.2%) had apathy. As expected, we observed some degree of overlap in symptoms, i.e. 20 (40.8%) subjects with depressed mood had anhedonia, 36 (73.5%) had anergia, and 20 (40.8%) had apathy. presents the results of the univariate logistic regression for each of the four neuropsychiatric symptoms. Associations significant at p < 0.01 are bolded in the table. To summarize, all four symptoms, depressed mood, anhedonia, anergia, and apathy were significantly more prevalent among subjects who were demented, while anergia and apathy were also more prevalent among cognitively impaired subjects, relative to unimpaired subjects. Neither age nor gender were associated with the presence of symptoms.
Univariate logistic regression analyses of the association between neuropsychiatric symptoms, demographic factors, cognitive status, and MRI regional volumes*
All four symptoms were associated with higher total volume of lacunes, as well as larger volume of lacunes in the white matter and in putamen. The presence of anhedonia, anergia, and apathy was also associated with smaller white matter volume. Smaller cortical gray matter volume was associated with anergia and apathy. A greater lacunar volume in the thalamus was associated with depressed mood. A greater volume of white matter hyperintensities was associated with anergia and anhedonia. Smaller hippocampal volume was associated with apathy only. Despite our presentation of the multivariate analyses in , we chose also to present the univariate results to be able to compare to other studies that did not adjust for other confounding variables.
Hypothesis-driven multivariate logistic regression adjusting for cognitive status, age, gender and education
Bivariate Pearson correlation coefficients among the MRI variables demonstrated weak-to-moderate correlations. Negative correlations were observed between the lacunar and white matter hyperintensities volumes and the white matter (correlations ranging from 0.1 to −0.26) and gray matter (correlations ranging from −0.04 to −0.49) volumes (Du et al., 2005
presents the results of the multivariate logistic regression adjusting for age, gender, education, and cognitive status. Adjustment for race did not change our results. Greater lacunar volume in the white matter and the diagnosis of dementia were associated with the presence of neuropsychiatric symptoms. After lacunar volume in the white matter was entered into the model, no other MRI variable was significantly associated with any neuropsychiatric symptom. In general, adjustment for each of the vascular conditions listed in (stroke, hypertension, hyperlipidemia, diabetes, congestive heart failure, myocardial infarction, coronary bypass surgery), the presence/absence of stroke-related hemiparesis, ataxia or extrapyramidal signs, and Blessed-Roth ADL score did not appreciably alter the odds ratios associated with the MRI variables (data not shown). For the anergia outcome, the estimate of association of lacunar volume in white matter was somewhat reduced with adjustment for a history of stroke (stroke-adjusted OR = 1.35, p = 0.03).
We did not find any significant interactions between cognitive status and MRI variables (data not shown), indicating that these MRI associations did not vary by cognitive status. We also repeated our multivariate analyses, confined to unimpaired subjects only. Although the results were in general not statistically significant due to small sample size, in all cases, the magnitude of the odds ratios (evaluating MRI associations with symptoms) were completely consistent with those reported in the total sample.
After combining all behavioral symptoms into a single global variable, 161 (60%) subjects had none of the four neuropsychiatric symptoms, 49 (18%) were positive on one symptom, 26 (10%) were positive on two symptoms, 18 (7%) were positive on three symptoms, and 12 (5%) subjects were positive on all four symptoms. In the univariate ordinal logistic regression analyses, all of the MRI variables (except for the lacunar volume in globus pallidus) were significantly associated with the presence of neuropsychiatric symptoms. However, in the multivariate analysis adjusting for cognitive status, age, gender and education, only the white matter lacunar volume was significantly associated with the global behavioral measure (OR = 1.63 per 0.03%, 95% CI 1.31, 2.02, p < 0.0001).