Deficits in learning are greater than memory dysfunction in preclinical Alzheimer’s disease

AbstractTo characterize the course of Alzheimer’s disease (AD) over a longer time interval, we aimed to construct a disease course model for the entire span of the disease using two separate cohorts ranging from preclinical AD to AD dementia. We modelled the progression course of 436 patients with AD continuum and investigated the effects of apolipoprotein E ε4 (APOE ε4) and sex on disease progression. To develop a model of progression from preclinical AD to AD dementia, we estimated Alzheimer’s Disease Assessment Scale-Cognitive Subscale 13 (ADAS-cog 13) scores. When calculated as the median of ADAS-cog 13 scores for each cohort, the estimated time from preclinical AD to MCI due to AD was 7.8 years and preclinical AD to AD dementia was 15.2 years. ADAS-cog 13 scores deteriorated most rapidly in women APOE ε4 carriers and most slowly in men APOE ε4 non-carriers (p < 0.001). Our results suggest that disease progression modelling from preclinical AD to AD dementia may help clinicians to estimate where patients are in the disease course and provide information on variation in the disease course by sex and APOE ε4 status.

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Cognitive Performance and Cerebrospinal Fluid Markers in Preclinical Alzheimer’s Disease: Results from the Gothenburg H70 Birth Cohort Studies

Journal of Alzheimer s Disease ◽

10.3233/jad-200751 ◽

2021 ◽

Vol 79 (1) ◽

pp. 225-235

Author(s):

Maya Arvidsson Rådestig ◽

Johan Skoog ◽

Henrik Zetterberg ◽

Jürgen Kern ◽

Anna Zettergren ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Cohort Studies ◽

Cognitive Performance ◽

Birth Cohort ◽

Population Based ◽

Tau Pathology ◽

Preclinical Alzheimer’S Disease ◽

Preclinical Ad

Background: We have previously shown that older adults with preclinical Alzheimer’s disease (AD) pathology in cerebrospinal fluid (CSF) had slightly worse performance in Mini-Mental State Examination (MMSE) than participants without preclinical AD pathology. Objective: We therefore aimed to compare performance on neurocognitive tests in a population-based sample of 70-year-olds with and without CSF AD pathology. Methods: The sample was derived from the population-based Gothenburg H70 Birth Cohort Studies in Sweden. Participants (n = 316, 70 years old) underwent comprehensive cognitive examinations, and CSF Aβ-42, Aβ-40, T-tau, and P-tau concentrations were measured. Participants were classified according to the ATN system, and according to their Clinical Dementia Rating (CDR) score. Cognitive performance was examined in the CSF amyloid, tau, and neurodegeneration (ATN) categories. Results: Among participants with CDR 0 (n = 259), those with amyloid (A+) and/or tau pathology (T+, N+) showed similar performance on most cognitive tests compared to participants with A-T-N-. Participants with A-T-N+ performed worse in memory (Supra span (p = 0.003), object Delayed (p = 0.042) and Immediate recall (p = 0.033)). Among participants with CDR 0.5 (n = 57), those with amyloid pathology (A+) scored worse in category fluency (p = 0.003). Conclusion: Cognitively normal participants with amyloid and/or tau pathology performed similarly to those without any biomarker evidence of preclinical AD in most cognitive domains, with the exception of slightly poorer memory performance in A-T-N+. Our study suggests that preclinical AD biomarkers are altered before cognitive decline.

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Using the A/T/N Framework to Examine Driving in Preclinical Alzheimer’s Disease

Geriatrics ◽

10.3390/geriatrics3020023 ◽

2018 ◽

Vol 3 (2) ◽

pp. 23 ◽

Cited By ~ 1

Author(s):

Catherine Roe ◽

Ganesh Babulal ◽

Sarah Stout ◽

David Carr ◽

Monique Williams ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Preclinical Alzheimer’S Disease

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Baseline Results: The Association Between Cardiovascular Risk and Preclinical Alzheimer’s Disease Pathology (ASCEND) Study

Journal of Alzheimer s Disease ◽

10.3233/jad-191103 ◽

2020 ◽

Vol 75 (1) ◽

pp. 109-117 ◽

Cited By ~ 1

Author(s):

Veena V. Kumar ◽

Hanfeng Huang ◽

Liping Zhao ◽

Danielle D. Verble ◽

Alexandra Nutaitis ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cardiovascular Risk ◽

Preclinical Alzheimer’S Disease

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Multimodal screening for neurodegeneration in preclinical Alzheimer’s disease using EEG, APOE4 genotype, neuropsychological and MRI data

Alzheimer s & Dementia ◽

10.1002/alz.044027 ◽

2020 ◽

Vol 16 (S5) ◽

Author(s):

Sinead Gaubert ◽

Federico Raimondo ◽

Marion Houot ◽

Marie‐Constance Corsi ◽

Lionel Naccache ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Preclinical Alzheimer’S Disease

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Preclinical Alzheimer's disease: A systematic review of the cohorts underlying the concept

Alzheimer s & Dementia ◽

10.1016/j.jalz.2016.12.003 ◽

2017 ◽

Vol 13 (4) ◽

pp. 454-467 ◽

Cited By ~ 42

Author(s):

Stéphane Epelbaum ◽

Rémy Genthon ◽

Enrica Cavedo ◽

Marie Odile Habert ◽

Foudil Lamari ◽

...

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Preclinical Alzheimer’S Disease

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Differential Cued-Stroop Performance in Cognitively Asymptomatic Older Adults with Biomarker-Identified Risk for Alzheimer’s Disease: A Pilot Study

Current Alzheimer Research ◽

10.2174/1567205015666180404170359 ◽

2018 ◽

Vol 15 (9) ◽

pp. 820-827 ◽

Cited By ~ 5

Author(s):

Ryan Van Patten ◽

Anne M. Fagan ◽

David A.S. Kaufman

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Cerebrospinal Fluid ◽

Stroop Task ◽

Coefficient Of Variation ◽

Reaction Times ◽

Preclinical Alzheimer’S Disease ◽

Cerebrospinal Fluid Biomarkers ◽

Accuracy Rates

Background: There exists a need for more sensitive measures capable of detecting subtle cognitive decline due to Alzheimer's disease. Objective: To advance the literature in Alzheimer’s disease by demonstrating that performance on a cued-Stroop task is impacted by preclinical Alzheimer's disease neuropathology. Method: Twenty-nine cognitively asymptomatic older adults completed a computerized, cued-Stroop task in which accuracy rates and intraindividual variability in reaction times were the outcomes of interest. Cerebrospinal fluid biomarkers of Aβ42 and tau were measured and participants were then grouped according to a published p-tau/Aβ42 cutoff reflecting risk for Alzheimer’s disease (preclinical Alzheimer's disease = 14; control = 15). Results: ANOVAs indicated that accuracy rates did not differ between the groups but 4-second delay incongruent color-naming Stroop coefficient of variation reaction times were higher in the preclinical Alzheimer’s disease group compared to the control group, reflecting increased within-person variability. Moreover, partial correlations showed no relationships between cerebrospinal fluid biomarkers and accuracy rates. However, increases in coefficient of variation reaction times correlated with decreased Aβ42 and increases in p-tau and the p-tau/Aβ42 ratio. Conclusion: Results supported the ability of the computerized, cued-Stroop task to detect subtle Alzheimer’s disease neuropathology using a small cohort of cognitively asymptomatic older adults. The ongoing measurement of cued-Stroop coefficient of variation reaction times has both scientific and clinical utility in preclinical Alzheimer’s disease.

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