Background: Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI; a preclinical stage of AD) are mostly associated with cognitive impairments. These cognitive challenges have been...Show moreBackground: Alzheimer’s disease (AD) and amnestic mild cognitive impairment (aMCI; a preclinical stage of AD) are mostly associated with cognitive impairments. These cognitive challenges have been linked to hippocampal decline. Prior work suggests additional motor impairments affecting fine and complex motor skills, motor coordination, and basic mobility. Recently impairments in motor learning have been proposed, concerning motor sequence learning (i.e., learning to perform a series of motor actions) and learning to learn (i.e., learning something about a learning process, which can be applied to another learning process). This master thesis investigates whether these two motor learning abilities are affected in AD and aMCI compared to healthy controls. In addition, we evaluate whether hippocampal volume, which is a known biomarker for AD, can predict motor sequence learning and learning to learn. Methods: A motor sequence learning task was performed by 28 AD patients, 33 aMCI patients, and 52 healthy controls. They were presented alternating blocks of randomly vs. sequentially ordered stimuli, to which they responded via button presses. The difference in reaction times of random vs. sequence blocks was used to measure motor learning. Two different sequences were presented, with one sequence measuring motor sequence learning in the first half of the task, and another sequence in the second half assessing learning to learn. Hippocampal volume was determined via a structural MRI scan. Results: Although patients with AD generally responded slower than individuals with aMCI and controls, no significant group differences were found in motor sequence learning and learning to learn. AD patients had smaller hippocampal volume than patients with aMCI and controls. Patients with aMCI displayed smaller volume than controls. However, hippocampal volume did not predict motor sequence learning measures. Conclusion: The findings indicate that motor sequence learning and learning to learn are intact in AD and aMCI. Hippocampal volume can be seen as a differentiating factor for the stages of AD progression of healthy individuals, aMCI, and AD. However, it did not predict motor learning measures. Rehabilitation programs should target on utilizing motor learning functions to improve activities of daily living in individuals with AD and aMCI.Show less
Vascular damage, like cerebral amyloid angiopathy (CAA), is a comorbidity in the majority of Alzheimer’s disease (AD) patients. Vascular reactivity has been introduced as a novel marker for...Show moreVascular damage, like cerebral amyloid angiopathy (CAA), is a comorbidity in the majority of Alzheimer’s disease (AD) patients. Vascular reactivity has been introduced as a novel marker for vascular damage in CAA. It is measured as the blood oxygen level dependent (BOLD) response in the visual cortex after visual stimulation. It may detect underlying vascular factors early in the disease, like in patients with subjective (SCI) or mild cognitive impairment (MCI). In these stages, SCI patients start to experience subjective cognitive complaints, whereas these can be objectified in MCI patients. The aim of this study is to measure and compare vascular reactivity in memory clinic patients and controls, and explore its association with cognition. We performed 3T MRI in 43 controls, 17 SCI, 20 MCI, and 12 AD patients and obtained 3D T1-weighted images, FLAIR, and visually stimulated BOLD fMRI scans. The main independent variable was patient group. Dependent variables were three vascular reactivity parameters time-to-peak, time-to-baseline, and amplitude of the BOLD response. Univariate linear models were performed to comparedifferences in vascular reactivity between memory clinic patients and controls, and separate patient groups and controls. Linear regression analyses were performed to explore the association between vascular reactivity and cognition. All analyses were corrected for age, gender, gray matter volume, white matter hyperintensities, and CAA. BOLD amplitudes were smaller in dementia and MCI (ps < .001), but not SCI patients (p = .77).Time-to-peak and time-to-baseline showed no differences between groups (ps > .07). Lower amplitude of the BOLD response was associated with poorer performance of global cognitive, memory, executive, and language functioning (ps < .04). Our findings demonstrate that dementia and MCI are associated with lower vascular reactivity, reflected as amplitude of the BOLD response. In our sample, lower vascular reactivity is also associated with poorer cognitive functioning. These results indicate that impaired vascular reactivity plays a key role early in dementia and is an independent contributor to cognitive decline. Potentially, vascular reactivity could be used as a marker for amyloid-beta and as an alternative way to quantify vascular damage. Ultimately, it could aid in the development of interventions focused on amyloid-beta removal and could serve as a marker for disease progression.Show less
