How attention and cholinergic signaling work in older adults with subjective cognitive decline

Attentional Mechanisms of Cognitive Compensation in Subjective Cognitive Decline

This project will test whether blocking a key brain chemical with mecamylamine disrupts attention more in older adults who feel their thinking is slipping than in those who do not, using cognitive tests and EEG.

Quick facts

• Phase: EARLY_PHASE1
• Study type: Interventional
• Enrollment: 80 (estimated)
• Ages: 55 Years and up
• Sex: All
• Sponsor: Vanderbilt University Medical Center (other)
• Locations: 1 site (Nashville, Tennessee)
• Trial ID: NCT06002477 on ClinicalTrials.gov

What this trial studies

This double-blind, randomized early-phase study will give cognitively normal adults with and without subjective cognitive decline either mecamylamine (an anticholinergic) or placebo across two visits and measure attention using the Attention Network Test and EEG. About 80 participants aged 55 and older will be enrolled, screened to exclude mild cognitive impairment and significant depression (MoCA ≥26, GDS <3) and to rule out medical contraindications. The primary approach compares changes in orienting attention ERP amplitudes and behavioral performance under drug versus placebo, testing whether those with greater subjective concern show larger declines when cholinergic function is blocked. Results aim to clarify whether enhanced cholinergic-supported compensatory attention activity helps preserve normal cognition in people with subjective cognitive decline.

Who should consider this trial

Good fit: Ideal candidates are non-smoking adults aged 55 or older who are cognitively normal on screening (MoCA ≥26, GDS <3), report subjective cognitive decline, and have no medical contraindications to mecamylamine.

Not a fit: People with mild cognitive impairment (MoCA <26), notable depressive symptoms (GDS ≥3), active smokers, those on contraindicated medications, or with primary neurological disorders are unlikely to be eligible or to receive benefit.

Why it matters

Potential benefit: If successful, the results could reveal early brain mechanisms tied to subjective cognitive decline and help guide future early detection or targeted intervention strategies.

How similar studies have performed: Prior pharmacological challenge studies using anticholinergic agents have successfully probed attention and EEG markers, though applying this approach specifically to subjective cognitive decline is relatively novel.

Eligibility criteria

Inclusion Criteria:

1. age ≥ 55
2. Montreal Cognitive Assessment (MoCA) \> 25 AND Global Deterioration Scale (GDS) rating \< 3
3. Non-smokers

Exclusion Criteria:

1. medical contraindications to the drug challenge
2. primary neurological disorder (such as stroke, epilepsy, etc.)

Where this trial is running

Nashville, Tennessee

• Vanderbilt University Medical Center — Nashville, Tennessee, United States (RECRUITING)

Study contacts

• Study coordinator: Kimberly Albert, PhD

Conditions: Subjective Cognitive Decline