Beruflich Dokumente
Kultur Dokumente
Disclosures
Nothing to disclose
Prodromal / Preclinical AD
Memory complaints by patient or family Progressive onset Normal or mildly impaired complex ADLs Amnestic syndrome of the hippocampal type Persistence of memory impairment at a subsequent assessment Absence of fully developed syndrome of dementia Exclusion of other disorders that may cause MCI (e.g., neuroimaging & biomarkers)
Annual Visit
Schmitt, et al. Neurology, 2000, 55:370-376; Markesbery, et al. Arch. Neurol. 2006, 63:38-46.
22 - 56%
Competing Risks
Events that alter the probability of experiencing (or observing) the outcome (Satagopan et al, 2004). Traditional survival analysis assumes censored observations are non-informative and ignorable.
Death alters the probability of observing dementia.
Markov chains - model the outcome of interest and competing events as mutually exclusive absorbing states to identify risk factors.
Probability models describing the random movements of a person among various finite states.
Movement between states depends only on the (immediate) prior state (1st order chain)
Time between successive observations is assumed to be constant. At each observation, persons may remain where they are or move to a new state until they are absorbed. Calculate the probability of remaining in or moving to a state vs. remaining in or returning to a state.
Age
increases risk for aMCI & mMCI
APOE-4
risk increased for aMCI
Education
lower education increases risk
for mMCI
Gender
no increased risk
Family Hx
no increased risk
Test-based MCI
At next visit:
aMCITB: Memory tests show reduced learning and/or delayed recall (-1.5 ) mMCITB: Praxis, executive, and/or language tests are also 1.5 below average MCICC: Consensus clinical criteria for are met for MCI
40.7% show no back transitions from aMCITB 43.8% show no back transitions from mMCITB 4.4% transition from aMCITB to MCICC or dementia 7.1% transition from aMCITB to MCICC or dementia
Abner, et al., Int. J. Alz. Dis., 2012
Hypertension (1.5X) increases mortality risk mMCITB (4.9X) increases risk for dementia and mortality (2.7X)
aMCITB & mMCITB: Biggest risk is Age Low education predicts transition to mMCITB Family history and female gender are protective for mMCITB MCICC: risks include ApoE4, age, low education aMCITB more than doubles the risk for MCICC mMCITB more than quadruples the risk for MCICC
Have you noticed a change in your memory since the last visit?
YES response implies the participant enters a state called SMC
55.7% answered YES on average 8.3 yrs. after study
entry
Determine risk factors associated with transitions into impaired states Assess neuropathology examinations for the 243 participants who came to autopsy
SMCCog-
SMC+ SMCCogCog+
SMC+ Cog+
SMCCog-
SMC+ Cog-
SMCCog+
SMC+ Cog+
Implications of SMC
Over half of volunteers have Subjective Memory Complaints during follow-up SMC accounts for most MCI/dementia transitions (OR = 2.8) SMC is no guarantee MCI/dementia will occur Identified risks affect the time and probability for transitions to occur
Autopsy results indicate a subset of individuals (but not all) have AD type pathology
Can inform the design of future prevention trials
Research Team:
Richard J. Kryscio & Frederick A. Schmitt (PI s) Erin Abner, Ph.D., Peter Nelson, M.D., Ph.D, Gregory Jicha, M.D., Ph.D., David Fardo, Ph.D.