Blood oxygenation level-dependent responses in neuromodulatory nuclei and their associations with attention and memory across age groups.

Using multi-echo blood oxygenation level-dependent (BOLD) neuroimaging, we examined lifespan differences in three subcortical nuclei important to the neuromodulation of cognition and target sites for early Alzheimer's pathogenesis in the isodendritic core: the locus coeruleus (LC) the major source of noradrenaline, the nucleus basalis of Meynert (NBM) the major source of acetylcholine, and the ventral tegmental area (VTA) the major source of dopamine. Seventy-one participants, from 19 to 86 years old (young n = 29, middle-aged, n = 18, and older n = 24), were tasked with memorizing visual images while monitoring auditory tones for a predefined target to assess attentional modulation of subsequent memory for the images. Young adults demonstrated a memory advantage for images paired with a target tone relative to no tone, which was diminished in middle age, and absent in older adults. Elevated NBM and VTA BOLD responses to subsequently remembered target-paired images were present in all groups but were selectively absent in the LC of older adults. Moreover, only LC activity explained individual variation in subsequent memory performance. Even though activity in multiple modulatory nuclei contributed, age-related change in the attentional boosting of memory was specifically tied to altered LC activity.