UC San Diego

Alzheimer's Disease (AD) is a devastating disorder that affects thousands of elderly adults each year. Impairments in memory are among the earliest and most profound symptoms of this disorder. At the time of diagnosis, most AD patients have already advanced into moderate to severe levels of memory impairment. In addition, the nature of the memory profile after conversion to AD has been studied extensively and has been well characterized as reflecting an encoding/storage impairment that affects both recall and recognition measures. However, what is not well known is the nature of the memory profile in individuals who are in a preclinical stage of AD (preAD). Do preAD individuals also display an encoding/storage memory profile, albeit to a mild degree? Or do they first pass through a stage of exhibiting a retrieval memory profile (similar to patients with subcortical disorders) before developing their hallmark encoding/storage profile? This knowledge is important for both improving early diagnosis of this disorder and for not misdiagnosing these individuals as having a primarily subcortical process prior to their conversion to AD. To address this question, the present study examined qualitative elements of episodic memory in three subject groups: (1) patients with AD; (2) former normal control subjects who converted to preAD and then were given AD diagnoses and were tested during their preAD stage; and (3) normal controls (NC) who did not display evidence of cognitive decline over time. The current research design was employed in a sample of 100 individuals diagnosed with probable Alzheimer's disease (mean age = 73.60; mean education = 14.71), 19 preAD patients (mean age = 73.60; mean education = 15.00) and 50 demographically-matched healthy older adults (mean age = 73.38; mean education = 15.16). The groups were not significantly different on age (p = .98), education (p = .34) or gender ([chi]² (2) = 2.16; p = .34). Episodic memory changes were studied using qualitative variables from the California Verbal Learning Test (CVLT) in the three subject groups over three serial assessments. The first CVLT administered at the ADRC was used as the subject's baseline test. The CVLT variables examined included Total Immediate Recall (TotImm), Long Delay Free Recall (LDFR), Delayed Retention Rate (RetRate), serial position effects, proactive interference, semantic clustering, intrusion errors, and Recognition Discriminability (RecogDis). Both a simple ANOVA at Time 1 and a repeated measures mixed model ANOVA were employed, with group as the between subject factor and time as the within subject factor. At Time 1, as expected, the AD group was significantly impaired relative to the NC group on the TotImm (p < .0005, d = 2.57), LDFR (p < .0005, d = 2.94, RetRate (p < .0005, d = 2.20), Total Intrusions (p < .0005, d = .96), and RecogDis (p < .0005, d = 2.85) measures. Importantly, on all five measures, the PreAD group performed significantly worse than the NC Group, TotImm (p < .0005, d = 1.56), LDFR (p < .0005, d = 1.57), RetRate (p < .0005, d = 1.20), Total Intrusions (p < .0005, d = .87) and RecogDis (p < .0005, d = 1.37) and significantly better than the AD group on the TotImm (p < .0005, d = 1.06), LDFR (p < .0005, d = 1.08), RetRate (p = .001, d = .90), and RecogDis (p < .0005, d = 1.17) measures. The one exception was that the PreAD group did not differ significantly from the AD group (p = .45 d = .42) in Total Intrusions; however, a small to medium effect size in the same direction suggests that the small preAD group size and associated limited power played a role in this analysis. In the repeated measures ANOVA, there were no significant interactions of time by group for any of the CVLT qualitative variables. There were significant main effects of time for both recency (p = .005, partial [eta]² = .05) and RecogDis (p = .009, partial eta]² = .03). As expected, the AD group was impaired on all qualitative variables as compared to the NC group (p < .0005) while the preAD group was impaired on proactive interference (p < .0005), semantic clustering (p < .0005) and RecogDis (p < .0005) compared to the NC group over time. Taken together, the findings from the study suggest that PreAD individuals do not first pass through a retrieval memory profile before converting to AD, but rather they generally display the classic encoding/storage profile, albeit to a mild degree, early in the disease course