The Karolinska NeuroCOVID study protocol: Neurocognitive impairment, biomarkers and advanced imaging in critical care survivors.

BACKGROUND: This is the study plan of the Karolinska NeuroCOVID study, a study of neurocognitive impairment after severe COVID-19, relating post-intensive care unit (ICU) cognitive and neurological deficits to biofluid markers and MRI. The COVID-19 pandemic has posed enormous health challenges to individuals and health-care systems worldwide. An emerging feature of severe COVID-19 is that of temporary and extended neurocognitive impairment, exhibiting a myriad of symptoms and signs. The causes of this symptomatology have not yet been fully elucidated. METHODS: In this study, we aim to investigate patients treated for severe COVID-19 in the ICU, as to describe and relate serum-, plasma- and cerebrospinal fluid-borne molecular and cellular biomarkers of immune activity, coagulopathy, cerebral damage, neuronal inflammation, and degeneration, to the temporal development of structural and functional changes within the brain as evident by serial MRI and extensive cognitive assessments at 3-12 months after ICU discharge. RESULTS: To date, we have performed 51 3-month follow-up MRIs in the ICU survivors. Of these, two patients (~4%) have had incidental findings on brain MRI findings requiring activation of the Incidental Findings Management Plan. Furthermore, the neuropsychological and neurological examinations have so far revealed varying and mixed patterns. Several patients expressed cognitive and/or mental concerns and fatigue, complaints closely related to brain fog. CONCLUSION: The study goal is to gain a better understanding of the pathological mechanisms and neurological consequences of this new disease, with a special emphasis on neurodegenerative and neuroinflammatory processes, in order to identify targets of intervention and rehabilitation.

Lifestyle Factors and Subjective Cognitive Impairment in Patients Seeking Help at a Memory Disorder Clinic: The Role of Negative Life Events.

BACKGROUND/AIMS: A large proportion of patients at memory disorders clinics are classified as having subjective cognitive impairment (SCI). Previous research has investigated whether particular lifestyle factors known to affect cognition can be useful in differentiating patients who do not show objective evidence of memory decline. There may also exist subgroups of patients with respect to lifestyle factors that could help clinicians to understand the patient group that presents to memory clinics. These may differ in diagnostic outcome. Very little is known about potential subgroups; however, but such information may help guide interventions and potentially eliminate unnecessary diagnostic procedures. The current study investigated patterns of lifestyle-related variables, including stress, sleep, sensory sensitivity, depression, and negative life events in patients presenting to a memory disorders clinic. The aim was to determine whether subgroups existed and whether it was possible to distinguish those with objectively impaired cognition. METHODS: One hundred and seventy-eight patients (mean age 58 years) from a University Hospital Memory Disorders Clinic. RESULTS: Cluster analysis identified three groups of lifestyle-related variables. Strong determinants of clusters were negative life events and age. Patients with a high number of negative life events also tended to have highest self-reported memory complaint, higher levels of stress, depression, and sensory sensitivity. However, they did not perform the worst on memory testing. In contrast, individuals who performed the worst on memory tests were older, tended to have the least memory complaints, and less negative lifestyle factors; this group also included the highest proportion of patients with mild cognitive impairment and had the lowest median amyloid A-beta 42 (Aß42). The group with the best cognitive performance were younger, included the highest proportion of patients with SCI and the highest median Aß42. On lifestyle variables, their ratings fell in between the other groups. CONCLUSIONS: Lifestyle subgroups of patients were determined by stress, emotional problems, and age. The groups were significantly associated with Aß42 and diagnostic outcome. This pattern may confound the differentiation between objective and subjective memory problems. Asking about lifestyle variables, in conjunction with neuropsychological testing, could potentially identify individuals who are not likely to have objective memory impairment and guide interventions.

Lifestyle Factors Are Important Contributors to Subjective Memory Complaints among Patients without Objective Memory Impairment or Positive Neurochemical Biomarkers for Alzheimer's Disease.

BACKGROUND/AIMS: Many patients presenting to a memory disorders clinic for subjective memory complaints do not show objective evidence of decline on neuropsychological data, have nonpathological biomarkers for Alzheimer's disease, and do not develop a neurodegenerative disorder. Lifestyle variables, including subjective sleep problems and stress, are factors known to affect cognition. Little is known about how these factors contribute to patients' subjective sense of memory decline. Understanding how lifestyle factors are associated with the subjective sense of failing memory that causes patients to seek a formal evaluation is important both for diagnostic workup purposes and for finding appropriate interventions and treatment for these persons, who are not likely in the early stages of a neurodegenerative disease. The current study investigated specific lifestyle variables, such as sleep and stress, to characterize those patients that are unlikely to deteriorate cognitively. METHODS: Two hundred nine patients (mean age 58 years) from a university hospital memory disorders clinic were included. RESULTS: Sleep problems and having much to do distinguished those with subjective, but not objective, memory complaints and non-pathological biomarkers for Alzheimer's disease. CONCLUSIONS: Lifestyle factors including sleep and stress are useful in characterizing subjective memory complaints from objective problems. Inclusion of these variables could potentially improve health care utilization efficiency and guide interventions.