Education as a Moderator of Help Seeking Behavior in Subjective Cognitive Decline.

OBJECTIVE: Disparities in Alzheimer disease (AD) and differences in help seeking (HS) across sociodemographic groups warrant public health concern. Research addressing such disparities must shift toward the earliest clinical manifestations of AD to optimize diagnosis, intervention and care planning. Subjective cognitive decline (SCD), a risk state for AD, provides an important context in which to examine sociodemographic-related disparities in HS. PARTICIPANTS AND METHODS: One hundred sixty-seven cognitively healthy older adults (M age =73, M education =16) (26.4% Black, Asian, or "Other") completed SCD questionnaire, HS questions, and mood measures (depression and anxiety). Binary logistic adjusted regressions examined: (a) the association between SCD and HS; and (b) the extent to which education moderated the relationship between SCD and HS. SCD [b = 0.06, SE=0.13, P <0.001, odds ratio=1.06, 95% CI (1.03, 1.08)] and education [b=0.32, SE=0.09, P <0.001, odds ratio=1.37, 95% CI (1.15, 1.64)] were independently associated with HS, with significant interaction between education and SCD on HS [b=0.2, SE=0.01, P =0.01, odds ratio=1.02, 95% CI (1.00, 1.03)]. CONCLUSIONS: Findings elucidate the importance of tailoring SCD-related psychoeducational resources depending on educational background as a preliminary stepping-stone in encouraging HS among older adults who may be at particular risk for developing dementia.

Nicotinic regulation of local and long-range input balance drives top-down attentional circuit maturation.

Cognitive function depends on frontal cortex development; however, the mechanisms driving this process are poorly understood. Here, we identify that dynamic regulation of the nicotinic cholinergic system is a key driver of attentional circuit maturation associated with top-down frontal neurons projecting to visual cortex. The top-down neurons receive robust cholinergic inputs, but their nicotinic tone decreases following adolescence by increasing expression of a nicotinic brake, Lynx1 Lynx1 shifts a balance between local and long-range inputs onto top-down frontal neurons following adolescence and promotes the establishment of attentional behavior in adulthood. This key maturational process is disrupted in a mouse model of fragile X syndrome but was rescued by a suppression of nicotinic tone through the introduction of Lynx1 in top-down projections. Nicotinic signaling may serve as a target to rebalance local/long-range balance and treat cognitive deficits in neurodevelopmental disorders.

Post-error recruitment of frontal sensory cortical projections promotes attention in mice.

The frontal cortex, especially the anterior cingulate cortex area (ACA), is essential for exerting cognitive control after errors, but the mechanisms that enable modulation of attention to improve performance after errors are poorly understood. Here we demonstrate that during a mouse visual attention task, ACA neurons projecting to the visual cortex (VIS; ACAVIS neurons) are recruited selectively by recent errors. Optogenetic manipulations of this pathway collectively support the model that rhythmic modulation of ACAVIS neurons in anticipation of visual stimuli is crucial for adjusting performance following errors. 30-Hz optogenetic stimulation of ACAVIS neurons in anesthetized mice recapitulates the increased gamma and reduced theta VIS oscillatory changes that are associated with endogenous post-error performance during behavior and subsequently increased visually evoked spiking, a hallmark feature of visual attention. This frontal sensory neural circuit links error monitoring with implementing adjustments of attention to guide behavioral adaptation, pointing to a circuit-based mechanism for promoting cognitive control.