In Sample 1, AD and OC groups were equivalent in age (P=0.653) but there were more men in the AD (41%) versus the OC (26%) groups (χ2=4.2, df=2, P=0.041) and the education level was lower in the AD (13.7±2.2) versus the OC (14.4±2.2) groups (t=2.12, df=178, P=0.035). In Sample 2, AD and OC groups did not differ in age (P=0.945) or sex (P>0.93) but the education level was lower in the AD (14.8±3.1) versus the OC (16.2±2.8) groups (t=4.65, df=367, P<0.001). Demographic and clinical data are presented in .
Demographic characteristics and amygdala and hippocampus volumes for Alzheimer's disease and older controls for samples 1 and 2
presents volumetric data for amygdala and hippocampus for AD and OC. Amygdala atrophy was substantial in subjects with very mild to mild AD. In Sample 1, the magnitudes of amygdala and hippocampal atrophy (compared to OC) were equivalent (P=0.3); in Sample 2, amygdala atrophy was slightly less prominent than hippocampal atrophy (t=3.40, df=175, P=0.0008). The effect size (Cohen's d) of AD on amygdala and hippocampus was respectively 1.0 and 1.0 for Sample 1 and 1.5 and 1.7 for Sample 2. The coefficients of variation for adjusted amygdala volume (Sample 1 = 19.3%; Sample 2 = 18.5%) were comparable to the coefficients of variation of adjusted hippocampus volume (Sample 1 = 18.3%; Sample 2 = 19.1%), indicating that there was similar variance in both structures in these patients. provides details on amygdala and hippocampal atrophy (cross-sectionally to clinical data acquisition).
Amygdala and hippocampus volumes and atrophy in Alzheimer's disease n comparison to older controls for samples 1 and 2
The magnitude of amygdala atrophy is similar to that of hippocampal atrophy in early Alzheimer's disease
Amygdala atrophy and hippocampal atrophy strongly paralleled each other at different levels of dementia severity and were essentially comparable at every level of the very mild to mild severity spectrum of the disease. These relationships are illustrated in . At CDR 0.5 (n=157, combining across samples), amygdala atrophy (-16.5%) was comparable to hippocampal atrophy (-17.2%) (P=0.5). At CDR 1 (n=107), amygdala atrophy (-23.5%) was slightly less prominent than hippocampal atrophy (-26.5%) (t=2.4, df=106, P=0.01).
Amygdala and hippocampal atrophy relate to MMSE scores and CDR-SB in very mild to mild AD
In linear regression analyses, amygdala volumes predicted scores on the MMSE (r=0.24, P=0.001) with a similar magnitude of correlation as hippocampal volumes (r=0.25, P<0.001). In contrast, amygdala volume was less strongly associated with CDR-SB (r=0.27, P<0.0003) than was the hippocampus (r=0.37, P<0.0000006). In linear regression analyses, amygdala volumes did not explain additional variance in the MMSE (regression equation r=0.27, P=0.001; β=0.135, delta r2=0.01, P=0.163) or in CDR-SB scores (regression equation r=0.37, P<0.000003; β=-0.059, delta r2=0.002, P=0.531) over and above hippocampal volumes.
There was no association between amygdala and any of the 5 targeted neuropsychiatric symptom domains (agitation/aggression, depression/dysthymia, anxiety, apathy/indifference, irritability), although exploratory analyses suggested several possible relationships worthy of future exploration. In post hoc exploratory analyses, greater amygdala atrophy was associated with more prominent aberrant motor behavior (AMB) (F=4.45, df=175, P=0.01; see ), but not with scores on other NPI items (delusions, hallucinations, euphoria/elation, disinhibition, sleep and appetite; all P values>0.1). illustrates the interesting potential relationships with anxiety and irritability, suggesting that subjects with greater anxiety (OC=1379±187; AD NPI anxiety: 2=1152±158, 1=1066±199, 0=1095±208) and irritability (OC=1379±187; AD NPI anxiety: 2=1122±162, 1=1068±177, 0=1098±218) might have less amygdala atrophy. Although these relations did not reach conventional levels of statistical significance, AD with NPI anxiety = 2 showed trend level significantly higher amygdala volume compared to NPI anxiety = 1 (one-sided t=1.382, df=173, P=0.085). Finally, neither the amygdala (r=0.080, P=0.292) nor the hippocampal volumes (r=0.020, P=0.796) were related to the NPI global score.
Relationships between amygdala volume and specific neuropsychiatric symptoms in AD, including irritability, anxiety, and aberrant motor behavior