Evidence from neuroimaging studies suggests a critical role of hippocampus and inferior frontal gyrus (IFG) in associative relative to item encoding. Here, we investigated similarities and differences in functional brain correlates for associative and item memory as a function of encoding instruction. Participants received either incidental (animacy judgments) or intentional encoding instructions while fMRI was employed during the encoding of associations and items. In a subsequent recognition task, memory performance of participants receiving intentional encoding instructions was higher compared with those receiving incidental encoding instructions. Furthermore, participants remembered more items than associations, regardless of encoding instruction. Greater brain activation in the left anterior hippocampus was observed for intentionally compared with incidentally encoded associations, although activity in this region was not modulated by the type of instruction for encoded items. Furthermore, greater activity in the left anterior hippocampus and left IFG was observed during intentional associative compared with item encoding. The same regions were related to subsequent memory of intentionally encoded associations and were thus task relevant. Similarly, connectivity of the anterior hippocampus to the right superior temporal lobe and IFG was uniquely linked to subsequent memory of intentionally encoded associations. Our study demonstrates the differential involvement of anterior hippocampus in intentional relative to incidental associative encoding. This finding likely reflects that the intent to remember triggers a specific binding process accomplished by this region.

Previous research shows that associative memory declines more than item memory in aging. Although the underlying mechanisms of this selective impairment remain poorly understood, animal and human data suggest that dopaminergic modulation may be particularly relevant for associative binding. We investigated the influence of dopamine (DA) receptor genes on item and associative memory in a population-based sample of older adults ( n = 525, aged 60 years), assessed with a face–scene item associative memory task. The effects of single-nucleotide polymorphisms of DA D1 ( DRD1 ; rs4532), D2 ( DRD2/ANKK1/Taq1A ; rs1800497), and D3 ( DRD3 / Ser9Gly ; rs6280) receptor genes were examined and combined into a single genetic score. Individuals carrying more beneficial alleles, presumably associated with higher DA receptor efficacy ( DRD1 C allele; DRD2 A2 allele; DRD3 T allele), performed better on associative memory than persons with less beneficial genotypes. There were no effects of these genes on item memory or other cognitive measures, such as working memory, executive functioning, fluency, and perceptual speed, indicating a selective association between DA genes and associative memory. By contrast, genetic risk for Alzheimer disease (AD) was associated with worse item and associative memory, indicating adverse effects of APOE ε4 and a genetic risk score for AD ( PICALM , BIN1 , CLU ) on episodic memory in general. Taken together, our results suggest that DA may be particularly important for associative memory, whereas AD-related genetic variations may influence overall episodic memory in older adults without dementia.