New study aims to unlock Alzheimer's secrets by tracking brain changes over time

Copied word for word from the study's registry entry, so the wording is the study team's rather than ours.

Inclusion Criteria: * Informed consent provided by the participant or, where applicable, Legally Authorized Representative (LAR) or other substitute decision-maker where permitted by applicable law, as described in Section 8.2. * Male or female, age ≥ 55 years at Screening. * Fluency of subject and study partner in English sufficient to complete all cognitive and self-report assessments without interpreter assistance. * Adequate visual and auditory acuity (with correction permitted) sufficient to complete neuropsychological testing. * Not pregnant or lactating. * Medications stable ≥ 4 weeks before screening. * GDS-15 \< 6 (i.e., 0-5 inclusive; no current significant depression). * Available study partner who has known the participant for ≥ 12 months, maintains \~10+ hours per week of in-person or telephone contact, and is willing to attend study visits and complete informant-rated assessments. * Willing to complete olfactory brushing, smell testing, and venous blood draw. * Willing to commit to baseline and follow-up visits across study duration. * In the opinion of the Investigator, able to comply with the protocol-specified visit schedule and procedures for the full study duration. Exclusion Criteria: * Current or active clinically significant neurological disorder (in the opinion of the Investigator) other than the disorders in the study arms, including but not limited to: * Parkinson's disease, dementia with Lewy bodies, frontotemporal dementia, progressive supranuclear palsy, corticobasal degeneration, Huntington's disease, prion disease, multi-infarct dementia, normal pressure hydrocephalus, brain tumor, seizure disorder, subdural hematoma, multiple sclerosis, significant head trauma with persistent deficits, or known structural brain abnormalities. * Active or unstable major psychiatric illness (DSM-5 schizophrenia spectrum, bipolar I, or severe major depressive disorder with active suicidality) within 6 months prior to Screening; history of schizophrenia at any time. * Psychotic features, agitation, or behavioral problems within the last 3 months that could interfere with protocol compliance. * Current substance use disorder (DSM-5 moderate or severe), or alcohol use disorder within 24 months prior to Screening. * Active malignancy under treatment, or malignancy with expected survival \< 30 months (excluding non-melanoma skin cancer and localized prostate cancer on active surveillance). * Participation in studies collecting neuropsychological measures more than once per year. * Presence of previous nasal surgery or other anatomical abnormalities that could interfere with the procedure on both sides of the nose, at the discretion of the clinician administering the Olfactory Brushing. * Active respiratory infection or recent history of respiratory infection within the past two weeks. * Known allergy or adverse reaction to topical anesthetics or decongestants used in the study (e.g., lidocaine, tetracaine, oxymetazoline). * Any other medical or psychiatric condition or lab abnormality that, in the opinion of the Investigator, might preclude participation or render the participant unsuitable for study enrollment. Cognitively Normal (CN) Additional Inclusion Criteria (CN) * No subjective cognitive complaint reported by participant AND no cognitive -complaint reported by study partner. * No current or prior clinical diagnosis of MCI, Alzheimer's disease, or any other dementia, and no current clinical diagnosis of a neurological or neuropsychiatric disease. * MMSE score ≥ 27 / 30 at Screening. * Global Clinical Dementia Rating (CDR) = 0 at Screening. * CDR Sum of Boxes (CDR-SB) = 0 at Screening. * Performance within 1.0 standard deviation of demographically adjusted norms on the Rey Auditory Verbal Learning Test (RAVLT) Delayed Recall. Additional Exclusion Criteria (CN) * Current or prior use of cholinesterase inhibitors (donepezil, rivastigmine, galantamine) or memantine for any indication. * Current or prior use of anti-amyloid monoclonal antibody disease-modifying therapy (aducanumab, lecanemab, donanemab, or any investigational anti-amyloid mAb). Mild Cognitive Impairment (MCI) Additional Inclusion Criteria (MCI) * Subjective cognitive complaint reported by participant OR partner-verified memory complaint reported by study partner. * MMSE score ≥ 24 and ≤ 30 at Screening. * Global CDR = 0.5 at Screening. * CDR-SB ≥ 0.5 and \< 3 at Screening; CDR Memory Box ≥ 0.5. * Performance ≥ 1.5 standard deviations below demographically adjusted norms on the RAVLT Delayed Recall (or equivalent episodic memory criterion per the Petersen / NIA-AA MCI framework). * Preserved general functional ability such that the participant does not meet criteria for dementia (i.e., does not meet AD criteria in Section 7.3). Alzheimer's Disease (AD) Additional Inclusion Criteria (AD) * Confirmed clinical diagnosis of probable Alzheimer's disease by a qualified specialist (cognitive neurologist, geriatric psychiatrist, or equivalent), consistent with NIA-AA 2011 (McKhann et al.) or NIA-AA 2018 Research Framework biological criteria. * MMSE score ≥ 16 and ≤ 26 at Screening. * Global CDR ≥ 1 at Screening. * CDR-SB ≥ 3 at Screening. * CDR Memory Box score ≥ 0.5 at Screening. * Partner-verified history of progressive cognitive decline of ≥ 6 months duration. * Functional impairment consistent with dementia, as documented on the CDR Functional Domains (Community Affairs, Home \& Hobbies, Personal Care); participant able to complete protocol.