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Claassen, J. A. H. R.

Publications and source records attributed to Claassen, J. A. H. R..

2 recordsLinked to original sources

Does early-stage Alzheimer's disease affect the dynamics of motor adaptation?

Alzheimers disease (AD) is characterized by an initial decline in declarative memory, while non-declarative memory processing remains relatively intact. Error-based motor adaptation is traditionally seen as a form of non-declarative memory, but recent findings suggest that it involves both fast, declarative and slow, non-declarative adaptive processes. If the declarative memory system shares resources with the fast process in motor adaptation, it can be hypothesized that the fast, but not the slow, process is disturbed in AD patients. To test this, we studied 20 early-stage AD patients and 21 age-matched controls of both sexes using a reach adaptation paradigm that relies on spontaneous recovery after sequential exposure to opposing force fields. Adaptation was measured using error clamps and expressed as an adaptation index (AI). Although patients with AD showed slightly lower adaptation to the force field than the controls, both groups demonstrated effects of spontaneous recovery. The time course of the AI was fitted by a hierarchical Bayesian two-state model in which each dynamic state is characterized by a retention and learning rate. Compared to controls, the retention rate of the fast process was the only parameter that was significantly different (lower) in the AD patients, confirming that the memory of the declarative, fast process is disturbed by AD. The slow adaptive process was virtually unaffected. Since the slow process learns only weakly from error, our results provide neurocomputational evidence for the clinical practice of errorless learning of everyday tasks in people with dementia.

neuroscience↗

Divergent associations of slow-wave sleep vs. REM sleep with plasma amyloid-beta

BackgroundRecent evidence shows that during slow-wave sleep (SWS), the brain is cleared from potentially toxic metabolites, such as the amyloid-beta protein. Poor sleep or elevated cortisol levels can worsen amyloid-beta clearance, potentially leading to the formation of amyloid plaques, a neuropathological hallmark of Alzheimers disease. Here, we explore how nocturnal neural and endocrine activity affects amyloid-beta fluctuations in the peripheral blood as a reflection of cerebral clearance. MethodsSimultaneous polysomnography and all-night blood sampling were acquired in 60 healthy volunteers aged 20-68 years old. Nocturnal plasma concentrations of two amyloid-beta species (amyloid-beta-40 and amyloid-beta-42), cortisol, and growth hormone were assessed every 20 minutes from 23:00-7:00. Amyloid-beta fluctuations were modeled with sleep stages, (non)-oscillatory power, and hormones as predictors while controlling for age and multiple comparisons. Time lags between the predictors and amyloid-beta ranged from 20 to 120min. FindingsThe amyloid-beta-40 and amyloid-beta-42 levels correlated positively with growth hormone concentrations, SWS proportion, slow-wave (0.3-4Hz) oscillatory and high-band (30-48Hz) non-oscillatory power, but negatively with cortisol concentrations and rapid eye movement sleep (REM) proportion measured 40-100min before (all t-values>|3|, p-values<0.003). Older participants showed higher amyloid-beta-40 levels. InterpretationSlow-wave oscillations are associated with higher plasma amyloid-beta levels, reflecting their contribution to cerebral amyloid-beta clearance across the blood-brain barrier. REM sleep is related to decreased amyloid-beta plasma levels; however, this link may reflect passive aftereffects of SWS and not REMs effects per se. Strong associations between cortisol, growth hormone, and amyloid-beta presumably reflect the sleep-regulating role of the corresponding releasing hormones. A positive association between age and amyloid-beta-40 may indicate that peripheral clearance becomes less efficient with age. Our study provides important insights into the specificity of different sleep features effects on brain clearance and suggests that cortisol nocturnal fluctuations may serve as a new marker of clearance efficiency.

neuroscience↗