Clinical and demographic factors modify the association between plasma phosphorylated tau-181 and cognition.

INTRODUCTION: Plasma phosphorylated tau181 (p-tau181) associations with global cognition and memory are clear, but the link between p-tau181 with other cognitive domains and subjective cognitive decline (SCD) across the clinical spectrum of Alzheimer's disease (AD) and how this association changes based on genetic and demographic factors is poorly understood. METHODS: Participants were drawn from the Alzheimer's Disease Neuroimaging Initiative and included 1185 adults aged >55 years with plasma p-tau181 and neuropsychological test data. Linear regression models related plasma p-tau181 to neuropsychological composite and SCD scores with follow-up models examining plasma p-tau181 interactions with cognitive diagnosis, APOE ε4 carrier status, age, and sex on cognitive outcomes. RESULTS: Higher plasma p-tau181 was associated with worse memory, executive functioning, and language abilities, and greater informant-reported SCD. Visuospatial abilities and self-report SCD were not associated with plasma p-tau181. Associations were generally stronger in MCI or dementia, APOE ε4 carriers, women, and younger participants. DISCUSSION: Higher levels of plasma p-tau181 are associated with worse neuropsychological test performance across multiple cognitive domains; however, these associations vary based on disease stage, genetic risk status, age, and sex.

Laterality in Parkinson's disease: A neuropsychological review.

Laterality of motor symptom onset in Parkinson's disease is both well-known and under-appreciated. Treatment of disorders that have asymmetric pathological features, such as stroke and epilepsy, demonstrate the importance of incorporating hemispheric lateralization and specialization into therapy and care planning. These practices could theoretically extend to Parkinson's disease, providing increased diagnostic accuracy and improved treatment outcomes. Additionally, while motor symptoms have generally received the majority of attention, non-motor features (e.g., autonomic dysfunction) also decrease quality of life and are influenced by asymmetrical neurodegeneration. Due to the laterality of cognitive and behavioral processes in the two brain hemispheres, analysis of hemibody side of onset can potentially give insight into expected symptom profile of the patient and allow for increased predictive accuracy of disease progression and outcome, thus opening the door to personalized and improved therapy in treating Parkinson's disease patients. This review discusses motor and non-motor symptoms (namely autonomic, sensory, emotional, and cognitive dysfunction) of Parkinson's disease in respect to hemispheric lateralization from a theoretical perspective in hopes of providing a framework for future research and personalized treatment.