Principal Investigator: Kevin Duff
Keywords: Alzheimer's , Mild Cognitive Impairment Department: Neurology
IRB Number: 00106377
Specialty: Neurology, Neurology, Neurology, Neurology, Neurology
Sub Specialties: Neuroimaging, Dementia, Geriatric Neurology, Alzheimer's Disease, Cognitive Disorders
Recruitment Status: Not yet recruiting

Contact Information

Kayla Suhrie
kayla.suhrie@hsc.utah.edu
801-581-8968

Brief Summary

The main objective of this new application is to demonstrate that individuals with low short-term practice effects (STPE) on repeated cognitive testing across one week are more likely to be identified as “positive” on amyloid imaging and other biomarkers associated with Alzheimer’s disease. This project would also examine if short-term practice effects and amyloid deposition differ across the disease spectrum in late adulthood by comparing older individuals who are cognitively intact to those with Mild Cognitive Impairment (MCI) and Alzheimer’s disease (AD). These findings would add to the supporting evidence of practice effects as a marker of diagnosis, prognosis, and treatment response in normal aging, MCI, and dementing illnesses. By realizing the aims of this pragmatic project, we would be able to offer more efficient screening of potential participants for clinical trials, which would reduce participant burden and financial costs associated with these trials. STPE could also be used to enrich trials with those more likely to progress and to monitor treatment benefit as a proximal outcome measure. STPE also have considerable clinical benefits for diagnosis and prognosis of cognitive disorders in late life.

The specific aims to be achieved in this project are:

1. Examine the relationship between STPE and: amyloid deposition, APOE status, hippocampal volumes, and functional connectivity, above and beyond baseline cognition.
Lower STPE will be correlated with greater β-amyloid neuritic plaque density in the brain assessed with [18F]flutemetamol PET imaging, and this relationship will hold even after considering baseline cognition. Lower STPE will also be associated with APOE e4 status, smaller hippocampi, and reduced functional connectivity, above and beyond baseline cognition.
 

2. Examine STPE as an indicator of progression across late life cognitive functioning.Cognitively intact older adults will display larger STPE than those with MCI, who will have larger STPE than those with AD. It is expected that AD biomarkers will show this same trend across groups.

 

3. Evaluate the classification accuracy of STPE in identifying subjects who are “amyloid positive.”
Identify cutoffs for STPE that optimally identify subjects who are amyloid positive vs. amyloid negative, as well as assess test operating characteristics (e.g., sensitivity, specificity, positive and negative predictive values, relative risk).

By achieving these aims, we expect to provide researchers with an inexpensive, non-invasive, and widely available screening tool (i.e., STPE) for predicting current amyloid positivity in cognitively intact and impaired seniors. These advancements could have significant savings in time and resources in conducting future clinical trials in MCI and AD dementia.

Inclusion Criteria

70 participants will be recruited in each of three cognitive categories: Cognitively Intact, Mild Cognitive Impairment (MCI) due to AD, and Probable Alzheimer's disease (AD) dementia. 

Participants will be categorized based on the diagnostic classification battery developed in the Alzheimer's Disease Neuroimaging Initiative (ADNI) study. 

 

Measure

Cutoff for intact

Cutoff for MCI

Cutoff for AD

MMSE

24 – 30

24 – 30

20 – 26

WMS-R Logical Memory II (Paragraph A only)

≥9 if educ ≥16 years

≥5 if educ 8-15 years

≥3 if educ 0-7 years

≤8 if educ ≥16 years

≤4 if educ 8-15 years

≤2 if educ 0-7 years

≤8 if educ ≥16 years

≤4 if educ 8-15 years

≤2 if educ 0-7 years

CDR (Overall)

0

0.5

0.5 or 1

GDS (15-item version)

<6

<6

<6

 

Inclusion Criteria:

  • 65 years of age or older
  • Cognitively Intact, OR diagnosed with amnestic Mild Cognitive Impairment (MCI) due to AD, OR diagnosed with Probable Alzheimer's disease (AD) dementia
    • Cognitively Intact participants must not meet criteria for MCI or dementia
    • MCI participants will be diagnosed with according to the NIA-AA core clinical criteria of Albert et al. (Albert et al., 2011) (e.g., concern regarding change in cognition, impairment in one or more cognitive domains, preservation of independence of functional abilities, not demented. Memory must be one of the cognitive domains that is impaired.
    • Probable AD dementia participants will be diagnosed according to the NIA-AA criteria of McKhann et al. (McKhann et al., 2011) (e.g., insidious onset, clear cut worsening of cognition, amnestic or non-amnestic presentation, no evidence of other causative conditions).
  • All participants must have a collateral source (e.g. spouse, adult child, caregiver, close friend) available to briefly comment on the cognitive abilities and daily functioning of the participant. If the participant is diagnosed with probable AD dementia, a legally authorized representative (e.g. spouse, adult child) must be available to provide informed consent for the participant.

Exclusion Criteria

  • History of major stroke, head injury with loss of consciousness of >30 minutes, or other neurological/systemic illness that may affect cognition
  • Current or past major psychiatric illness (e.g., schizophrenia, bipolar affective disorder)
  • History of substance abuse
  • Current use of antipsychotics or anticonvulsant medications
  • Known allergic or hypersensitivity reactions to previously administered radiopharmaceuticals.
  • Requiring monitored sedation or anesthesia for PET or MRI scanning.
  • Claustrophobia to a degree that the individual cannot undergo PET or MRI imaging
  • History of metal injury which precludes the individual from undergoing MRI imaging
  • Evidence of stroke or mass lesion on a CT or MRI scan
  • History of radiation therapy to the brain
  • History of significant major medical illnesses, such as cancer or AIDS. 
  • Inadequate vision, hearing, and manual dexterity to participate in the cognitive assessments.
  • Currently pregnant
  • 15-item Geriatric Depression Scale score of >5
  • Clinical Dementia Rating score of >1
  • Mini Mental State Examination score of <20
  • Currently randomized in a clinical drug trial and potentially receiving experimental anti– amyloid agents