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Objectives: We describe the intracranial pressure dynamics andcerebral vasomotor reactivity in a coronavirus disease 2019 patient with acute encephalitis treated with cerebrospinal fluid drainage and therapeutic plasma exchange.

Data Sources: Coronavirus disease ICU, Uppsala University Hospital,Sweden.

Study Selection: Case report.

Data Extraction: Radiology, intracranial pressure, intracranial compliance (correlation between intracranial pressure amplitude and mean intracranial pressure), cerebral vasomotor reactivity (pressure reactivity index), arterial blood pressure, cerebrospinal fluid chemistry, and treatment.

Data Synthesis: None.

Conclusions: This is the first reported case of intracranial pressure monitoring in a patient with acute encephalitis following corona virus disease 2019. Intracranial pressure data exhibited a high incidence of plateau waves with intracranial pressure insults above 40 mm Hg that required cerebrospinal fluid drainage. Intracranial compliance was low, and pressure reactivity was intact. It is probable that the combination of low intracranial compliance and intact pressure autoregulation explain the high degree of plateau intracranial pressure waves and intracranial pressure variability.

Introduction: The purpose of our study was to compare visual rating and volumetry of brain atrophy in an elderly population over a 5‐year period and compare findings with cognitive test results.

Materials and Methods: Two hundred and one subjects were examined with magnetic resonance imaging (MRI) of the brain. Visual rating and volumetry were performed in all subjects at ages 75 and 80. Cognitive function at both time points was assessed with the Mini‐Mental State Examination (MMSE) and Trail Making Tests A and B (TMT‐A and TMT‐B). Changes in visual rating and volumetry were compared with changes in cognitive test.

Results: A correlation was found between visual rating of medial temporal lobe atrophy (MTA) and hippocampal volumetry at both time points (rs = −.42 and rs = −.49, p < .001, respectively). The correlation between visual rating of posterior atrophy (PA); frontal atrophy (F‐GCA) and volumetry of these brain regions was significant only at age 80 (rs = −.16, p = .02 for PA and rpb = .19, p = .006 for F‐GCA). Visual rating showed only a minimal progression of regional atrophy at age 80, whereas volumetry showed 2%–5% decrease in volume depending on brain region. Performance in the MMSE, TMT‐A, and TMT‐B was virtually unchanged between ages 75 and 80.

Conclusion: We found a mild age‐associated decrease in regional brain volumes in this healthy cohort with well‐preserved cognitive functions. Visual assessment may not be sufficient for detecting mild progression of brain atrophy due to normal aging, whereas volumetry is more sensitive to capture these subtle changes.

During aging, brain changes are not homogeneous throughout the entire brain, but are related to changes in the morphology of neurons, as well as to changes in the tissue density, and are specific to each region of the brain. Dementia is a broad category of brain disorders with a set of symptoms including memory, visual-spatial and language problems. Most types of dementia are slowly progressing, and by the time the person shows signs of the disorder, processes in the brain are already advanced. Dementia reduces not only the person’s ability to perform everyday activities, it also increases mortality rates significantly. Because of the increasing incidence of dementia, possible prevention and treatment of dementia as early as possible are essential.

The aim of the PhD project is to compare a quantitative and qualitative image analysis of regional cerebral atrophy with cognitive function in the elderly persons.

In paper I, 58 persons participated (84–88 years old) from the ULSAM (Uppsala Longitudinal Study of Adult Men) cohort. They underwent CT of the brain, cognitive testing and LP. This study showed that AD biomarkers seem to be less informative in subjects with an advanced age.

In papers II–IV, the cohort included subjects from the PIVUS (Prospective Investigation of the Vasculature in Uppsala Seniors) study.

Paper II showed that at age 75, gender and education are confounders for MTA rating. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later.

Paper III showed that automated rating of MTA could be used in clinical practice to support the radiological evaluation. Automated rating of PA and F-GCA should be tested in future studies.

In paper IV, we found a mild age-associated decrease in regional brain volumes in this healthy cohort with well-preserved cognitive and executive functions.

In conclusion, the included studies in this thesis compare regional atrophy grades in the brain on CT and MRI and clinical data and provide knowledge that may be used in future investigations that aim to detect dementia in its early stages.

OBJECTIVES: To find cut-off values for different medial temporal lobe atrophy (MTA) measures (right, left, average, and highest), accounting for gender and education, investigate the association with cognitive performance, and to compare with decline of cognitive function over 5 years in a large population-based cohort.

METHODS: Three hundred and ninety 75-year-old individuals were examined with magnetic resonance imaging of the brain and cognitive testing. The Scheltens's scale was used to assess visually MTA scores (0-4) in all subjects. Cognitive tests were repeated in 278 of them after 5 years. Normal MTA cut-off values were calculated based on the 10th percentile.

RESULTS: Most 75-year-old individuals had MTA score ≤2. Men had significantly higher MTA scores than women. Scores for left and average MTA were significantly higher in highly educated individuals. Abnormal MTA was associated with worse results in cognitive test and individuals with abnormal right MTA had faster cognitive decline.

CONCLUSION: At age 75, gender and education are confounders for MTA grading. A score of ≥2 is abnormal for low-educated women and a score of ≥2.5 is abnormal for men and high-educated women. Subjects with abnormal right MTA, but normal MMSE scores had developed worse MMSE scores 5 years later.

KEY POINTS: • Gender and education are confounders for MTA grading. • We suggest cut-off values for 75-year-olds, taking gender and education into account. • Males have higher MTA scores than women. • Higher MTA scores are associated with worse cognitive performance.

BACKGROUND: The Alzheimer's disease (AD) brain displays atrophy with amyloid-β (Aβ) and tau deposition, whereas decreased Aβ42 and increased tau are measured in cerebrospinal fluid (CSF). The aim of this study was to relate cognitive performance to the degree of brain atrophy, CSF biomarker levels and neuropathology in a cohort of aged men.

METHODS: Fifty-eight 86-92-year-old men from the Uppsala Longitudinal Study of Adult Men (ULSAM) cohort underwent cognitive testing, brain computed tomography and lumbar puncture. Atrophy was graded with established scales. Concentrations of CSF Aβ42, t-tau and p-tau were measured by ELISA. Thirteen brains were examined post mortem.

RESULTS: Forty-six of the individuals were considered non-demented, whereas twelve were diagnosed with dementia, either at baseline (n = 4) or during follow-up (n = 8). When comparing subjects with and without dementia, there were no differences in the degree of atrophy, although the mini mental state examination (MMSE) scoring correlated weakly with the degree of medial temporal atrophy (MTA) (p = 0.04). Moreover, the CSF biomarker levels did not differ significantly between healthy (n = 27) and demented (n = 8) subjects (median values 715 vs 472 pg/ml for Aβ42, 414 vs 427 pg/ml for t-tau and 63 vs 60 pg/ml for p-tau). Similarly, there were no differences in the biomarker levels between individuals with mild (n = 24) and severe (n = 11) MTA (median values 643 vs 715 pg/ml for Aβ42, 441 vs 401 pg/ml for t-tau and 64 vs 53 pg/ml for p-tau). Finally, the neuropathological changes did not correlate with any of the other measures.

CONCLUSION: In this cohort of aged men only a weak correlation could be seen between cognitive performance and MTA, whereas the various neuroradiological, biochemical and neuropathological measures did not correlate with each other. Thus, AD biomarkers seem to be less informative in subjects of an advanced age.

PURPOSE: Functional imaging is becoming increasingly important for the detection of neurodegenerative disorders. Perfusion MRI with arterial spin labeling (ASL) has been reported to provide promising diagnostic possibilities but is not yet widely used in routine clinical work. The aim of this study was to compare, in a clinical setting, the visual assessment of subtracted ASL CBF maps with and without additional smoothing, to FDG-PET data.

METHODS: Ten patients with a clinical diagnosis of dementia and 11 age-matched cognitively healthy controls were examined with pseudo-continuous ASL (pCASL) and 18F-Fluorodeoxyglucose positron emission tomography (FDG-PET). Three diagnostic physicians visually assessed the pCASL maps after subtraction only, and after postprocessing using Gaussian smoothing and GLM-based beta estimate functions. The assessment scores were compared to FDG PET values. Furthermore, the ability to discriminate patients from healthy elderly controls was assessed.

RESULTS: Smoothing improved the correlation between visually assessed regional ASL perfusion scores and the FDG PET SUV-r values from the corresponding regions. However, subtracted pCASL maps discriminated patients from healthy controls better than smoothed maps. Smoothing increased the number of false-positive patient identifications. Application of beta estimate functions had only a marginal effect.

CONCLUSION: Spatial smoothing of ASL images increased false positive results in the discrimination of hypoperfusion conditions from healthy elderly. It also decreased interreader agreement. However, regional characterization and subjective perception of image quality was improved.