Locus-coeruleus Function in Normal Elderly and AD Risk

ID#: NCT04403165

Age: 60 - 75 years

Gender: All

Healthy Subjects: Accepts Healthy Volunteers

Study Phase: N/A

Recruitment Status: Recruiting

Start Date: August 06, 2020

End Date: August 01, 2022

Contact Information:
Dishari Azad
Ricardo Osorio
Summary: Growing evidence suggests that Alzheimer's disease (AD) pathological changes begin decades before clinical symptoms and tau abnormalities in the locus coeruleus (LC) can be observed since midlife. We have previously demonstrated functional vulnerability of the LC to aging and stress, as well as an association between higher CSF tau and impaired sleep phenomena influenced by the LC. We now aim to test whether LC dysfunction can be measured in preclinical AD stages by LC targeted imaging, and whether it objectively affects sleep architecture and attention. We will test this hypothesis in 30 cognitively normal older adults by performing a full clinical evaluation, one night of polysomnography, a lumbar puncture to obtain cerebrospinal fluid, [11C]MRB PET-MR, and attention testing. This study has the potential to identify a new mechanism by which tau pathology contributes to sleep and attention dysfunction and may provide a new therapeutic target for AD prevention.

- Male and female subjects with normal cognition and 60-75 years of age will be enrolled.

- Subjects will be within normal limits on neurological and psychiatric examinations. All subjects enrolled will have both a Clinical Dementia Rating (CDR)=0 and a MMSE>27.

- All subjects will have had a minimum of 12 years of education. Among underrepresented group (URG) subjects, >80% of the elderly individuals coming to the NYU-ADRC meet this criterion. (The education restriction reduces performance variance on cognitive test measures and improves the sensitivity for detecting pathology and disease progression using the robust norms available at the NYU ADRC. Given the majority of subjects will meet this criterion we do not consider this a major selection bias or generalization limitation for this study).

- An informed family member or life-partner (preferably bed-partner) will be interviewed to confirm the reliability of the subject interview.

Exclusion Criteria:

- History of brain tumor, MRI evidence of brain damage or brain disease including significant trauma, hydrocephalus, seizures, mental retardation or other serious neurological disorder (e.g. Parkinson's disease or other movement disorders). Subjects with a Fazekas scale >2 will be excluded.

- Significant history of alcoholism or drug abuse.

- History of psychiatric illness (e.g., schizophrenia, bipolar, PTSD, or life-long history of major depression).

- Geriatric Depression Scale (short form)>5.

- Insulin dependent diabetes.

- Evidence of clinically relevant cardiac, pulmonary, endocrine or hematological conditions.

- Physical impairment of such severity as to adversely affect the validity of psychological testing.

- Any prosthetic devices (e.g., pacemaker or surgical clips) that constitutes a hazard for MRI imaging.

- History of a first-degree family member with early onset (age <60 years) dementia.

- Irregular sleep-wake rhythms (based on the actigraphy recordings) or significant OSA (AHI3a%>/=15).

- Medications affecting cognition or sleep.