scholarly journals Monthly At-Home Computerized Cognitive Testing to Detect Diminished Practice Effects in Preclinical Alzheimer's Disease

2022 ◽  
Vol 13 ◽  
Author(s):  
Roos J. Jutten ◽  
Dorene M. Rentz ◽  
Jessie F. Fu ◽  
Danielle V. Mayblyum ◽  
Rebecca E. Amariglio ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Pet Imaging ◽  
Cognitive Testing ◽  
Practice Effects ◽  
Aging Brain ◽  
Amyloid Burden ◽  
Preclinical Ad ◽  
At Home

Introduction: We investigated whether monthly assessments of a computerized cognitive composite (C3) could aid in the detection of differences in practice effects (PE) in clinically unimpaired (CU) older adults, and whether diminished PE were associated with Alzheimer's disease (AD) biomarkers and annual cognitive decline.Materials and Methods:N = 114 CU participants (age 77.6 ± 5.0, 61% female, MMSE 29 ± 1.2) from the Harvard Aging Brain Study completed the self-administered C3 monthly, at-home, on an iPad for one year. At baseline, participants underwent in-clinic Preclinical Alzheimer's Cognitive Composite-5 (PACC5) testing, and a subsample (n = 72, age = 77.8 ± 4.9, 59% female, MMSE 29 ± 1.3) had 1-year follow-up in-clinic PACC5 testing available. Participants had undergone PIB-PET imaging (0.99 ± 1.6 years before at-home baseline) and Flortaucipir PET imaging (n = 105, 0.62 ± 1.1 years before at-home baseline). Linear mixed models were used to investigate change over months on the C3 adjusting for age, sex, and years of education, and to extract individual covariate-adjusted slopes over the first 3 months. We investigated the association of 3-month C3 slopes with global amyloid burden and tau deposition in eight predefined regions of interest, and conducted Receiver Operating Characteristic analyses to examine how accurately 3-month C3 slopes could identify individuals that showed >0.10 SD annual decline on the PACC-5.Results: Overall, individuals improved on all C3 measures over 12 months (β = 0.23, 95% CI [0.21–0.25], p < 0.001), but improvement over the first 3 months was greatest (β = 0.68, 95% CI [0.59–0.77], p < 0.001), suggesting stronger PE over initial repeated exposures. However, lower PE over 3 months were associated with more global amyloid burden (r = −0.20, 95% CI [−0.38 – −0.01], p = 0.049) and tau deposition in the entorhinal cortex (r = −0.38, 95% CI [−0.54 – −0.19], p < 0.001) and inferior-temporal lobe (r = −0.23, 95% CI [−0.41 – −0.02], p = 0.03). 3-month C3 slopes exhibited good discriminative ability to identify PACC-5 decliners (AUC 0.91, 95% CI [0.84–0.98]), which was better than baseline C3 (p < 0.001) and baseline PACC-5 scores (p = 0.02).Conclusion: While PE are commonly observed among CU adults, diminished PE over monthly cognitive testing are associated with greater AD biomarker burden and cognitive decline. Our findings imply that unsupervised computerized testing using monthly retest paradigms can provide rapid detection of diminished PE indicative of future cognitive decline in preclinical AD.

O2-06-04: DOES β-AMYLOID BURDEN PREDICT COGNITIVE DECLINE STATUS IN ADULTS AT RISK FOR ALZHEIMER'S DISEASE?

2006 ◽  
Vol 14 (7S_Part_11) ◽  
pp. P632-P634
Author(s):  
Heather L. Shouel ◽  
Rebecca L. Koscik ◽  
Lindsay R. Clark ◽  
Sara Elizabeth Berman ◽  
Brad T. Christian ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Cognitive Decline ◽  
Amyloid Burden ◽  
Β Amyloid

scholarly journals SHORT-TERM PRACTICE EFFECTS AND AMYLOID DEPOSITION: PROVIDING INFORMATION ABOVE AND BEYOND BASELINE COGNITION

2017 ◽  
pp. 1-6
Author(s):  
K. Duff ◽  
D.B. Hammers ◽  
B.C.A. Dalley ◽  
K.R. Suhrie ◽  
T.J. Atkinson ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Clinical Trials ◽  
Test Scores ◽  
Amyloid Deposition ◽  
Cognitive Testing ◽  
Practice Effects ◽  
Cognitive Test ◽  
Cognitive Tests ◽  
Short Term

Background: Practice effects, which are improvements in cognitive test scores due to repeated exposure to testing materials, may provide information about Alzheimer’s disease pathology, which could be useful for clinical trials enrichment. Objectives: The current study sought to add to the limited literature on short-term practice effects on cognitive tests and their relationship to amyloid deposition on neuroimaging. Participants: Twenty-seven, non-demented older adults (9 cognitively intact, 18 with mild cognitive impairment) received amyloid imaging with 18F-Flutemetamol, and two cognitive testing sessions across one week to determine practice effects. Results: A composite measure of 18F-Flutemetamol uptake correlated significantly with all seven cognitive tests scores on the baseline battery (r’s = -0.61 – 0.59, all p’s<0.05), with higher uptake indicating poorer cognition. Practice effects significantly added to the relationship (above and beyond the baseline associations) with 18F-Flutemetamol uptake on 4 of the 7 cognitive test scores (partial r’s = -0.45 – 0.44, p’s<0.05), with higher uptake indicating poorer practice effects. The odds ratio of being “amyloid positive” was 13.5 times higher in individuals with low practice effects compared to high practice effects. Conclusions: Short-term practice effects over one week may be predictive of progressive dementia and serve as an affordable screening tool to enrich samples for preventative clinical trials in Alzheimer’s disease.

scholarly journals Genetic Effects on Longitudinal Cognitive Decline During the Early Stages of Alzheimer's Disease

2021 ◽  
Author(s):  
Atul Kumar ◽  
Maryam Shoai ◽  
Sebastian Palmqvist ◽  
Erik Stomrud ◽  
John Hardy ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Genome Wide Association Study ◽  
Early Stage ◽  
Cognitive Change ◽  
Preclinical Ad ◽  
Genome Wide ◽  
A Genome ◽  
Polygenic Scores

Abstract Background Cognitive decline in early-stage Alzheimer’s disease (AD) may depend on genetic variability. Methods In the Swedish BioFINDER study, we used polygenic scores (PGS) (for AD, intelligence and educational attainment), and genetic variants (in a genome-wide association study [GWAS]) to predict longitudinal cognitive change (measured by MMSE) over a mean of 4.2 years. We included 555 β-amyloid (Aβ) negative cognitively unimpaired (CU) individuals, 206 Aβ-positive CU (preclinical AD), 110 Aβ-negative mild cognitive impairment (MCI) patients, and 146 Aβ-positive MCI patients (prodromal AD). Results Polygenic scores for AD (in Aβ-positive individuals) and intelligence (independent of Aβ-status) were associated with cognitive decline. Eight genes were associated with cognitive decline in GWAS (3 independent of Aβ-status). Conclusions AD risk genes may influence cognitive decline in early AD, while genes related to intelligence may modulate cognitive decline irrespective of disease. Therapies targeting the implicated biological pathways may modulate the clinical course of AD.

scholarly journals Evidence for Reduced Autobiographical Memory Episodic Specificity in Cognitively Normal Middle-Aged and Older Individuals at Increased Risk for Alzheimer’s Disease Dementia

2018 ◽  
Vol 24 (10) ◽  
pp. 1073-1083 ◽  
Author(s):  
Matthew D. Grilli ◽  
Aubrey A. Wank ◽  
John J. Bercel ◽  
Lee Ryan
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Older Individuals ◽  
Autobiographical Memories ◽  
Middle Aged ◽  
Cognitively Normal ◽  
Preclinical Ad ◽  
Increased Risk ◽  
And Gender

AbstractObjectives: Alzheimer’s disease (AD) typically eludes clinical detection for years, if not decades. The identification of subtle cognitive decline associated with preclinical AD would not only advance understanding of the disease, but also provide clinical targets to assess preventative and early intervention treatments. Disrupted retrieval of detailed episodic autobiographical memories may be a sensitive indicator of subtle cognitive decline, because this type of memory taxes a core neural network affected by preclinical AD neuropathology. Methods: To begin to address this idea, we assessed the episodic specificity of autobiographical memories retrieved by cognitively normal middle-aged and older individuals who are carriers of the apolipoprotein E ε4 allele – a population at increased risk for subtle cognitive decline related to neuropathological risk factors for AD. We compared the ε4 carriers to non-carriers of ε4 similar in age, education, and gender. Results: The ε4 carriers did not perform worse than the non-carriers on a comprehensive battery of neuropsychological tests. In contrast, as a group, the ε4 carriers generated autobiographical memories that were reduced in “internal” or episodic details relative to non-carriers. Conclusions: These findings support the notion that reduced autobiographical episodic detail generation may be a marker of subtle cognitive decline associated with AD. (JINS, 2018, 24, 1073–1183)

Interaction Between BDNF Val66Met and APOE4 on Biomarkers of Alzheimer’s Disease and Cognitive Decline

2020 ◽  
Vol 78 (2) ◽  
pp. 721-734
Author(s):  
Cynthia M. Stonnington ◽  
Stefanie N. Velgos ◽  
Yinghua Chen ◽  
Sameena Syed ◽  
Matt Huentelman ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Brain Activity ◽  
Amyloid Β ◽  
Hippocampal Volume ◽  
Rate Of Change ◽  
Plaque Burden ◽  
Amyloid Burden ◽  
Hippocampus Volume

Background: Whether brain-derived neurotrophic factor (BDNF) Met carriage impacts the risk or progression of Alzheimer’s disease (AD) is unknown. Objective: To evaluate the interaction of BDNF Met and APOE4 carriage on cerebral metabolic rate for glucose (CMRgl), amyloid burden, hippocampus volume, and cognitive decline among cognitively unimpaired (CU) adults enrolled in the Arizona APOE cohort study. Methods: 114 CU adults (mean age 56.85 years, 38% male) with longitudinal FDG PET, magnetic resonance imaging, and cognitive measures were BDNF and APOE genotyped. A subgroup of 58 individuals also had Pittsburgh B (PiB) PET imaging. We examined baseline CMRgl, PiB PET amyloid burden, CMRgl, and hippocampus volume change over time, and rate of change in cognition over an average of 15 years. Results: Among APOE4 carriers, BDNF Met carriers had significantly increased amyloid deposition and accelerated CMRgl decline in regions typically affected by AD, but without accompanying acceleration of cognitive decline or hippocampal volume changes and with higher baseline frontal CMRgl and slower frontal decline relative to the Val/Val group. The BDNF effects were not found among APOE4 non-carriers. Conclusion: Our preliminary studies suggest that there is a weak interaction between BDNF Met and APOE4 on amyloid-β plaque burden and longitudinal PET measurements of AD-related CMRgl decline in cognitively unimpaired late-middle-aged and older adults, but with no apparent effect upon rate of cognitive decline. We suggest that cognitive effects of BDNF variants may be mitigated by compensatory increases in frontal brain activity—findings that would need to be confirmed in larger studies.

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