W3 Flashcards
what is the key goal of research design in aging, ND, and dementia?
provide both general-group and person-centered info about long-term aging pathways leading toward relatively healthier brain aging or sustained typical brain aging or towards CI and dementia
what is the key focus of research in aging and AD?
designing, collecting, analyzing and interpreting data
- reflect and display common patterns and diverse heterogeneities of individual and group cog and brain health aging
what is the key research interest of research?
identifying individual and group differences and changes in transitions, directions, RF, predictors (biomarkers) and responses (RR)
what are the interests associated with “change”?
description of change: what, when, how
explanation of change: why
differential change: degree of dynamic heterogeneity
modifiability of change: can we change the direction of change?
what is the fundamental feature of research design?
time -> change occurs over time
- explicit research attention to framing, studying, displaying or approx relevant aspects of group or individual differences may change over time
what do research designs require?
time-structured design and change-sensitive measures
what is the goal of research design?
detect and measure direction, rate, variability, responsivity
what are the two basic types of research design?
cross-sectional design
longitudinal design
what is CSL?
comparing diff groups on one occasion of measurement
what is LONG design?
following all individuals in one or more group across more than one time point or across clinical status transitions
(NA->MCI)
what are the strengths and weaknesses of CSL?
S: quick and inexpensive
W: detects group or age diff only, historical cohort effects
what are the strength and weaknesses of LONG?
S: age changes and transitions detectable
W: time consuming, expensive, historical cohort effects
what is the historical cohort effect?
aggregate of individuals who experiences same aging-related risk or protection exposures
- same historical time interval and as similar dosages of experience
- “Birth Cohort”
is historical and clinical cohort the same?
no
- clinical refers to groups of individuals classified according to objective clinical characteristics
what is the long-term effect of historical cohort effect?
persons may develop differently depending on cohort membership
what creates cohort differences?
major historical events or trends
on a graph how do you differentiate CSL from longitudinal?
CSL has no connecting points and LONG has connecting points
what is the limitation for CSL?
no direct info on intraindividual change and variability, or individual differences in change
what is the limitation for LONG?
direct indication of age changes but no necessarily the same profile across individuals, successive cohorts, diff generations
what is a limitation for both designs?
descriptive - no mechanisms or predictors
what is the complexity for inter-individuals differences?
no single normative path
what is the complexity for intra-individual variability?
within domain individuals can vary
what is the purpose of a theoretical model?
representation or framework for how things might work and how they might be explored
- roadmap
what are the methods for eval models?
usefulness in representing research results and providing direction for productive and theoretically important new studies and results
what do modern models do?
attempt to represent dynamic and interactive complexities of transitions in brain and cog aging
what are the 2 models of NA-MCI-AD transitions?
linear vs dynamic polygon
compare original dynamic polygon model vs recent models
og: broad integrative with important implications (dynamics and potential)
recent: suggest future steps, even broader view, dynamic interactions, broader health biomarkers
what are some applications for the polygon model?
early detection
intervention
what do the new models of AD pathways imply?
- time structured: dynamic, long-term
- interactive: expected, tested, within/across RF and biomarker domains
- modifiable and non-modifiable distinction
- multiple outcomes: CN, CI, CND
- intervention targets
what is the CCNA?
Canadian Consortium on Neurodegeneration in Aging
- 2020 Roadmap for ADRD research
what are the 2 types of large-scale epidemiological studies?
cross-sectional sequential design
long sequential design
what are the advantages of doing Long sequential designs?
- acceleration: “band” of aging covered can expand rapidly
- epidemiological progress: range of biomarkers, multiple modalities of predictors and mechanisms of actual change and outcomes can be tested
- early detection
- transition tracking
what is the disadvantage of doing Long sequential design?
v expensive and time consuming
what is considered to be observational research?
CSL
LONG
LONG-SEQ
BIG DATA
what is considered to be intervention research?
experience
training
therapeutic
what is a “gold standard” intervention?
RCT
- precise design features for supporting intervention efficacy
what is RCT?
specialized experiment for determining efficacy of observationally indicated and theoretically supported intervention for treating, curing or delaying adverse condition
what is the key feature of RCT?
random allocation to specific treatment or placebo
why do randomization?
eliminate bias or selection effects and help mask/blinding treatments
what are the requirements for RCT to occur?
-registered to world-wide clinical trials data base
- go on record with protocol paper
- document and follow procedural rules
what are the 2 new identifiable phases between NA and AD?
SCD
MCI
what is SCD?
subjective cognitive decline
- self-reported awareness
what is the challenges of SCD?
measurement
veridicality
predictive
what is SMD?
subset of SCD
what is MCI?
mild cog impairment
- awareness plus objective evidence and clinical judgement regarding multiple factors
is MCI a disease?
no it is a classification not a diagnosis
what are the issues with MCI emergence?
can later segment of PreAD be differentiated, classified, validated and clinically useful?
what is the goal of MCI research?
seeking earlier identifiable phases for reliable signals of impending ad
how to verify MCI?
evidence for reliability (repeat) and validity (success of predication)
how is MCI research useful?
organize understanding of early AD risk, operationalizing preclinical period, providing valid target group for intervention
who was important for MCI research?
ronald petersen
what was Petersen’s goal?
develop models for predicting dementia from cog impairment signs in otherwise NA
what did Petersen question?
the boundary zones between NA and AD
what was the review in 2000?
MCI emerging as preferred term to define cog impairment that may be prodrome to AD
what was Petersen’s role and goals?
- developer and early leader in MCI
- identify transitions between NA to MCI and then predict transitions from MCI to AD
what was Petersen’s approach?
5 + 1
- memory complaint
- objective memory impairment
- intact general cognition
- preserved activities of daily living
- not demented
** clinical judgement may be involved in final classification of an individual
what was the MCI status report?
- lots of research
- assessment progress in testing clinical prediction validity
- clinical differentiation -> more than one MCI for AD and ADRD
what is amnestic MCI?
memory-specific MCI most closely related to AD and outcome
what are the challenges for MCI?
- MCI status should predict AD better than NA and SCD groups
- improve classification precision -> reduce uncertainty
- dilemma in NA-MCI-AD transitions
what was the contingent conclusion?
MCI is heterogenous classification
-> growing evidence of diversity in MCI: clinical presentation, NDD-related subtypes, pathways to and from MCI
what are the 3 challenges associated with heterogeneity in MCI?
- how to optimally weight various clinical-cog criteria for more precise MCI classification
- how to eval and account for diversity
- how to consider and integrate objective info, sub reports, informant reports, skilled clinical judgement
what is MCI and what is MCI not?
MCI is not a clinical destination or aging end-state
- not a disease state or diagnosis
MCI is a transition phase with heterogeneity and multi-directionality
- more objective than SCD or pre-clinical
- less objective and certain than AD
- probabilistic but represented elevated risk for AD
what kind of research design is recommended for MCI?
LONG
what are some assessment and measurements for MCI?
- cognitive domains (memory, global impair, processing speed)
- biomarkers and RF
- multi doses and interactions
who discovered MCI “reversion”?
Katie Palmer and Backman
what was the MCI reversion project called?
Kungsholmen project
what was the Kungsholmen project?
13 yr LONG pop-based study of aging and dementia
plus 75 age sample
age-related risk for MCI and AD
what did Palmer discover?
prevalence of 15% of baseline non-demented participants
heterogenous development
MCI 3x more likely to progress to dementia than 85% healthy older adults
what are the characteristics of MCI reversion?
- reversion of SCD -> pre-MCI-classification with differential trajectories and unclear prospects
- SCD has fluid boundaries and variable change patterns
why can MCI reverse?
more heterogenous than AD
complex process that reflects individualized changes
not a final outcome
what was the goal of the reversion study?
discover characteristics of individuals with MCI who revert to NA status and what happens next
how many reverted, continued, converted?
16
64
20
what predicts reversion?
MMSE
clinical dementia rating scale
functional activities
APOE status
what happens post-reversion?
MCI-NA reverters greater risk for later cog decline
what was the first consensus about MCI?
phase of AD when experiencing gradually progressive cog decline that results from accumulation of AD pathology in brain
what was the second consensus about MCI?
amnestic and non-amn cognition should be tested objectively
- LONG cognitive change essential or subjectivelu through informants
- eval biomarkers and RD
what did Brainerd explore?
APOE and MCI
- relatively reliable predictor of MCI
what did Jack explore?
preclinical MCI with cascade theories of AD development
- cascade leading from MCI and AD and progressing to AD could be apparent in MCI and accelerated or delayed by AD RF
- moderator: stratification by APOE e4
- risk predictors: amyloid deposition, neuronal injury, neuroimaging evidence
what can large LONG studies do?
- examine genetic, ad biomarker, vascular risk MCI factors
- predict status, emergence, reversion and stability
- follow and test transitions and trajectories
what does APOE e4 do?
intensified the effect of other AD risk factors on MCI emergence
