The basal forebrain cholinergic system linking olfaction and cognitive function: From basic studies to clinical application

Olfactory dysfunction is a common aspect of normal aging. It is also an early symptom of Alzheimer’s disease (AD). The olfactory bulb, the first processing station of olfactory information in the brain, receives cholinergic basal forebrain input, as does the neocortex and hippocampus contributing cognition and memory, respectively. This study aimed to clarify (1) the role of cholinergic input to the olfactory bulb in adult and aged rats, (2) the relationship between olfaction and cognitive function in older adults.In both adult and aged rats, under anesthesia, unilateral olfactory nerve stimulation produced frequency-dependent increases in blood flow in the olfactory bulb ipsilateral to the stimulus. In adult rats, intravenous injection of nicotinic acetylcholine receptor agonist, nicotine, potentiated the olfactory bulb blood flow response to nerve stimulation. The potentiating effect of nicotine shown in adult rats was greatly reduced in old rats.In the community-dwelling older adults, the relationship between olfactory identification ability and cognitive functions, including attention and discrimination, were assessed. All participants were able to identify the rose odor between steps 2 and 7. Participants with a higher olfactory threshold (≥5) declined more in the attention and discrimination abilities, compared to those with a lower threshold (≤4). Because both attention and discrimination abilities are related to the basal forebrain cholinergic system, our results suggest that olfactory impairment links to the decline in cognitive function relating the cholinergic system. Olfactory stimulation may be a useful intervention for older adults preventing cognitive impairment by activating cholinergic system.