Spaced Retrieval Compensates for the Associative Memory Impairment in Older Adults

Background: Computerized cognitive assessments may improve Alzheimer’s disease (AD) secondary prevention trial efficiency and accuracy. However, they require validation against standard outcomes and relevant biomarkers. Objective: To assess the feasibility and validity of the tablet-based Computerized Cognitive Composite (C3). Design: Cross-sectional analysis of cognitive screening data from the A4 study (Anti-Amyloid in Asymptomatic AD). Setting: Multi-center international study. Participants: Clinically normal (CN) older adults (65-85; n=4486). Measurements: Participants underwent florbetapir-Positron Emission Tomography for Aβ+/- classification. They completed the C3 and standard paper and pencil measures included in the Preclinical Alzheimer’s Cognitive Composite (PACC). The C3 combines memory measures sensitive to change over time (Cogstate Brief Battery-One Card Learning) and measures shown to be declining early in AD including pattern separation (Behavioral Pattern Separation Test- Object- Lure Discrimination Index) and associative memory (Face Name Associative Memory Exam- Face-Name Matching). C3 acceptability and completion rates were assessed using qualitative and quantitative methods. C3 performance was explored in relation to Aβ+/- groups (n=1323/3163) and PACC. Results: C3 was feasible for CN older adults to complete. Rates of incomplete or invalid administrations were extremely low, even in the bottom quartile of cognitive performers (PACC). C3 was moderately correlated with PACC (r=0.39). Aβ+ performed worse on C3 compared with Aβ- [unadjusted Cohen’s d=-0.22 (95%CI: -0.31,-0.13) p<0.001] and at a magnitude comparable to the PACC [d=-0.32 (95%CI: -0.41,-0.23) p<0.001]. Better C3 performance was observed in younger, more educated, and female participants. Conclusions: These findings provide support for both the feasibility and validity of C3 and computerized cognitive outcomes more generally in AD secondary prevention trials.

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TRAJECTORIES OF SUBJECTIVE MEMORY IMPAIRMENT AND OBJECTIVE COGNITIVE DECLINE IN U.S. OLDER ADULTS

Innovation in Aging ◽

10.1093/geroni/igz038.743 ◽

2019 ◽

Vol 3 (Supplement_1) ◽

pp. S205-S205

Author(s):

Hanzhang Xu ◽

Matthew E Dupre ◽

Bei Wu

Keyword(s):

Older Adults ◽

Cognitive Decline ◽

Memory Impairment ◽

Subjective Memory ◽

Subjective Memory Impairment ◽

Logistic Regressions ◽

Dual Trajectories ◽

Nationally Representative ◽

Low Educated ◽

Retirement Study

Abstract We examined the dual trajectories of subjective memory impairment (SMI) and objective cognitive decline and their associated factors in U.S. older adults. We used data from the Health and Retirement Study which includes a nationally representative sample of 19,408 Americans age 65 and older from 1998 to 2016. Trajectories of SMI and objective cognitive decline were simultaneously characterized using a group-based trajectory model and multinomial logistic regressions were used to assess factors associated with the dual-trajectory typologies. Four dual-trajectories were identified: “minimal SMI and stable-low cognitive decline” (33.1% of respondents); “minimal SMI with accelerated cognitive decline” (28.2%); “significant SMI with moderate cognitive decline” (21.0%); and “moderate SMI with steady cognitive decline” (17.6%). Being male, minority, low educated, living alone, and having comorbidities were associated with trajectories featuring greater SMI or more rapid deterioration in cognition. The results suggest complex co-occurring changes in subjective memory and objective cognition in older adults.

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Latent patterns of task‐related functional connectivity relate to hyperactivation and associative memory impairment in SCD + and MCI

Alzheimer s & Dementia ◽

10.1002/alz.038002 ◽

2020 ◽

Vol 16 (S5) ◽

Author(s):

Nick Corriveau‐Lecavalier ◽

Natasha Rajah ◽

Samira Mellah ◽

Sylvie Belleville ◽

Keyword(s):

Functional Connectivity ◽

Associative Memory ◽

Memory Impairment

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The importance of the ventromedial prefrontal cortex for associative memory in older adults: A latent structural equation analysis

NeuroImage ◽

10.1016/j.neuroimage.2019.116475 ◽

2020 ◽

Vol 209 ◽

pp. 116475

Author(s):

Yvonne Brehmer ◽

Jonna Nilsson ◽

Rasmus Berggren ◽

Florian Schmiedek ◽

Martin Lövdén

Keyword(s):

Older Adults ◽

Prefrontal Cortex ◽

Associative Memory ◽

Structural Equation ◽

Ventromedial Prefrontal Cortex ◽

Structural Equation Analysis ◽

Equation Analysis

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LTP and memory impairment caused by extracellular Aβ and Tau oligomers is APP-dependent

eLife ◽

10.7554/elife.26991 ◽

2017 ◽

Vol 6 ◽

Cited By ~ 48

Author(s):

Daniela Puzzo ◽

Roberto Piacentini ◽

Mauro Fá ◽

Walter Gulisano ◽

Domenica D Li Puma ◽

...

Keyword(s):

Associative Memory ◽

Memory Impairment ◽

Long Term Potentiation ◽

Neuronal Uptake ◽

Common Mechanism ◽

Tau Oligomers ◽

Term Potentiation ◽

Induced Defects ◽

Oligomeric Forms

The concurrent application of subtoxic doses of soluble oligomeric forms of human amyloid-beta (oAβ) and Tau (oTau) proteins impairs memory and its electrophysiological surrogate long-term potentiation (LTP), effects that may be mediated by intra-neuronal oligomers uptake. Intrigued by these findings, we investigated whether oAβ and oTau share a common mechanism when they impair memory and LTP in mice. We found that as already shown for oAβ, also oTau can bind to amyloid precursor protein (APP). Moreover, efficient intra-neuronal uptake of oAβ and oTau requires expression of APP. Finally, the toxic effect of both extracellular oAβ and oTau on memory and LTP is dependent upon APP since APP-KO mice were resistant to oAβ- and oTau-induced defects in spatial/associative memory and LTP. Thus, APP might serve as a common therapeutic target against Alzheimer's Disease (AD) and a host of other neurodegenerative diseases characterized by abnormal levels of Aβ and/or Tau.

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