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Extensive memory testing improves prediction of progression to MCI in late middle age.

ABSTRACT: Introduction:Predicting risk for Alzheimer's disease when most people are likely still biomarker negative would aid earlier identification. We hypothesized that combining multiple memory tests and scores in middle-aged adults would provide useful, and non-invasive, prediction of 6-year progression to MCI. Methods:We examined 849 men who were cognitively normal at baseline (mean age ± SD = 55.69 ± 2.45). Results:California Verbal Learning Test learning trials was the best individual predictor of amnestic MCI (OR = 4.75). A latent factor incorporating seven measures across three memory tests provided much stronger prediction (OR = 9.88). This compared favorably with biomarker-based prediction in a study of much older adults. Discussion:Neuropsychological tests are sensitive and early indicators of MCI risk at an age when few individuals are likely to have yet become biomarker positive. The single best measures may appear time- and cost-effective, but 30 additional minutes of testing and use of multiple scores within tests provide substantially improved prediction.

SUBMITTER: Gustavson DE

PROVIDER: S-EPMC7148418 | biostudies-literature | 2020

REPOSITORIES: biostudies-literature

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Extensive memory testing improves prediction of progression to MCI in late middle age.

Gustavson Daniel E DE Elman Jeremy A JA Sanderson-Cimino Mark M Franz Carol E CE Panizzon Matthew S MS Jak Amy J AJ Reynolds Chandra A CA Neale Michael C MC Lyons Michael J MJ Kremen William S WS

Alzheimer's & dementia (Amsterdam, Netherlands) 20200411 1

<h4>Introduction</h4>Predicting risk for Alzheimer's disease when most people are likely still biomarker negative would aid earlier identification. We hypothesized that combining multiple memory tests and scores in middle-aged adults would provide useful, and non-invasive, prediction of 6-year progression to MCI.<h4>Methods</h4>We examined 849 men who were cognitively normal at baseline (mean age ± SD = 55.69 ± 2.45).<h4>Results</h4>California Verbal Learning Test learning trials was the best in ...[more]

PMID: 32284960

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Project description:This study investigated differences in retrospective cognitive trajectories between amyloid and tau PET biomarker stratified groups in initially cognitively unimpaired participants sampled from the Wisconsin Registry for Alzheimer's Prevention. One hundred and sixty-seven initially unimpaired individuals (baseline age 59 ± 6 years; 115 females) were stratified by elevated amyloid-β and tau status based on 11C-Pittsburgh compound B (PiB) and 18F-MK-6240 PET imaging. Mixed effects models were used to determine if longitudinal cognitive trajectories based on a composite of cognitive tests including memory and executive function differed between biomarker groups. Secondary analyses investigated group differences for a variety of cross-sectional health and cognitive tests, and associations between 18F-MK-6240, 11C-PiB, and age. A significant group × age interaction was observed with post hoc comparisons indicating that the group with both elevated amyloid and tau pathophysiology were declining approximately three times faster in retrospective cognition compared to those with just one or no elevated biomarkers. This result was robust against various thresholds and medial temporal lobe regions defining elevated tau. Participants were relatively healthy and mostly did not differ between biomarker groups in health factors at the beginning or end of study, or most cognitive measures at study entry. Analyses investigating association between age, MK-6240 and PiB indicated weak associations between age and 18F-MK-6240 in tangle-associated regions, which were negligible after adjusting for 11C-PiB. Strong associations, particularly in entorhinal cortex, hippocampus and amygdala, were observed between 18F-MK-6240 and global 11C-PiB in regions associated with Braak neurofibrillary tangle stages I-VI. These results suggest that the combination of pathological amyloid and tau is detrimental to cognitive decline in preclinical Alzheimer's disease during late middle-age. Within the Alzheimer's disease continuum, middle-age health factors likely do not greatly influence preclinical cognitive decline. Future studies in a larger preclinical sample are needed to determine if and to what extent individual contributions of amyloid and tau affect cognitive decline. 18F-MK-6240 shows promise as a sensitive biomarker for detecting neurofibrillary tangles in preclinical Alzheimer's disease.

Project description:BackgroundExercise interventions to prevent dementia and delay cognitive decline have gained considerable attention in recent years. Human and animal studies have demonstrated that regular physical activity targets brain function by increasing cognitive reserve. There is also evidence of structural changes caused by exercise in preventing or delaying the genesis of neurodegeneration. Although initial studies indicate enhanced cognitive performance in patients with mild cognitive impairment (MCI) following an exercise intervention, little is known about the effect of an extensive, controlled and regular exercise regimen on the neuropathology of patients with MCI. This study aims to determine the effects of an extensive exercise programme on the progression of MCI.Methods/designThis randomised controlled clinical intervention study will take place across three European sites. Seventy-five previously sedentary patients with a clinical diagnosis of MCI will be recruited at each site. Participants will be randomised to one of three groups. One group will receive a standardised 1-year extensive aerobic exercise intervention (3 units of 45 min/week). The second group will complete stretching and toning (non-aerobic) exercise (3 units of 45 min/week) and the third group will act as the control group. Change in all outcomes will be measured at baseline (T0), after six months (T1) and after 12 months (T2). The primary outcome, cognitive performance, will be determined by a neuropsychological test battery (CogState battery, Trail Making Test and Verbal fluency). Secondary outcomes include Montreal Cognitive Assessment (MoCA), cardiovascular fitness, physical activity, structural changes of the brain, quality of life measures and measures of frailty. Furthermore, outcome variables will be related to genetic variations on genes related to neurogenesis and epigenetic changes in these genes caused by the exercise intervention programme.DiscussionThe results will add new insights into the prevailing notion that exercise may slow the rate of cognitive decline in MCI.Trial registrationClinicalTrials.gov NCT02913053.

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Extensive memory testing improves prediction of progression to MCI in late middle age.

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Extensive memory testing improves prediction of progression to MCI in late middle age.

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