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Background: Depression and dementia are known to be associated. The identification of characteristics distinguishing depression prodromal to dementia from other depressive symptoms would be of value for early identification of dementia. The study of risk factors for depressive symptoms prodromal to dementia could improve preventive care and provide clues to the causes of dementia.

Method: Dementia-free 82-year-old participants were stratified into groups that did (n = 126) and did not (n = 378) subsequently develop dementia. Examinations took place from 2003 to 2005 and follow-up ended 1 January 2015. Their baseline characteristics and depressive symptoms, measured using the 15-item Geriatric Depression Scale (GDS-15), were compared. Multivariate regression analyses were performed for the two groups separately, with the total GDS-15 score as the dependent variable.

Results: The groups did not differ significantly in answers to any of the GDS-15 questions, or mean +/- SD score, which was 2.4 +/- 2.5 among those who developed dementia and 2.1 +/- 2.3 among those who did not. (p = 0.33). Stroke before the age of 82 years and the inability to use stairs had significant impacts on the GDS-15 scores in both groups. For those who did not develop dementia, age, dependence in activities of daily living, and cancer also had significant impacts. Cancer had opposite associations with depressive symptoms in the two groups.

Conclusions: No difference was found in depressive symptoms preceding and not preceding dementia using the GDS-15. The results suggest that risk factors for depressive symptoms may differ depending on whether they precede dementia.

Background: Evidence indicates that herpes simplex virus (HSV) participates in the pathogenesis of Alzheimer's disease (AD). Objective: We investigated AD and dementia risks according to the presence of herpesvirus antibodies in relation to antiherpesvirus treatment and potential APOE epsilon 4 carriership interaction. Methods: This studywas conducted with 1002 dementia-free 70-year-olds living in Sweden in 2001-2005 who were followed for 15 years. Serum samples were analyzed to detect anti-HSV and anti-HSV-1 immunoglobulin (Ig) G, anti-cytomegalovirus (CMV) IgG, anti-HSV IgM, and anti-HSV and anti-CMV IgG levels. Diagnoses and drug prescriptions were collected from medical records. Cox proportional-hazards regression models were applied. Results: CumulativeADand all-cause dementia incidences were 4% and 7%, respectively. Eighty-two percent of participants were anti-HSV IgG carriers, of whom 6% received anti-herpesvirus treatment. Anti-HSV IgG was associated with a more than doubled dementia risk (fully adjusted hazard ratio = 2.26, p = 0.031). No significant association was found with AD, but the hazard ratio was of the same magnitude as for dementia. Anti-HSV IgM and anti-CMV IgG prevalence, anti-herpesvirus treatment, and anti-HSV and -CMV IgG levels were not associated with AD or dementia, nor were interactions between anti-HSV IgG and APOE epsilon 4 or anti-CMV IgG. Similar results were obtained for HSV-1. Conclusions: HSV (but not CMV) infection may be indicative of doubled dementia risk. The low AD incidence in this cohort may have impaired the statistical power to detect associations with AD.

INTRODUCTION:

Vervets are non-human primates that share high genetic homology with humans and develop amyloid beta (A beta) pathology with aging. We expand current knowledge by examining A beta pathology, aging, cognition, and biomarker proteomics.

METHODS:

Amyloid immunoreactivity in the frontal cortex and temporal cortex/hippocampal regions from archived vervet brain samples ranging from young adulthood to old age was quantified. We also obtained cognitive scores, plasma samples, and cerebrospinal fluid (CSF) samples in additional animals. Plasma and CSF proteins were quantified with platforms utilizing human antibodies.

RESULTS:

We found age-related increases in A beta deposition in both brain regions. Bioinformatic analyses assessed associations between biomarkers and age, sex, cognition, and CSF A beta levels, revealing changes in proteins related to immune-related inflammation, metabolism, and cellular processes.

DISCUSSION:

Vervets are an effective model of aging and early-stage Alzheimer's disease, and we provide translational biomarker data that both align with previous results in humans and provide a basis for future investigations.

Background: Neuroinflammatory processes have been suggested to play a role in the pathophysiology of neurodegenerative diseases and post-hemorrhagic hydrocephalus, but have rarely been investigated in patients with idiopathic normal pressure hydrocephalus (iNPH). The aim of this study was to investigate whether levels of inflammatory proteins in CSF are different in iNPH compared to healthy controls and patients with selected neurodegenerative disorders, and whether any of these markers can aid in the differential diagnosis of iNPH.

Methods: Lumbar CSF was collected from 172 patients from a single center and represented iNPH (n = 74), Alzheimer's disease (AD) (n = 21), mild cognitive impairment (MCI) due to AD (n = 21), stable MCI (n = 22), frontotemporal dementia (n = 13), and healthy controls (HC) (n = 21). Levels of 92 inflammatory proteins were analyzed using a proximity extension assay. As a first step, differences between iNPH and HC were investigated, and proteins that differed between iNPH and HC were then compared with those from the other groups. The linear regressions were adjusted for age, sex, and plate number.

Results: Three proteins showed higher (MCP-1, p = 0.0013; CCL4, p = 0.0008; CCL11, p = 0.0022) and one lower (PD-L1, p = 0.0051) levels in patients with iNPH compared to HC. MCP-1 was then found to be higher in iNPH than in all other groups. CCL4 was higher in iNPH than in all other groups, except in MCI due to AD. PD-L1 was lower in iNPH compared to all other groups, except in stable MCI. Levels of CCL11 did not differ between iNPH and the differential diagnoses. In a model based on the four proteins mentioned above, the mean area under the receiver operating characteristic curve used to discriminate between iNPH and the other disorders was 0.91.

Conclusions: The inflammatory cytokines MCP-1 and CCL4 are present at higher-and PD-L1 at lower-levels in iNPH than in the other investigated diagnoses. These three selected cytokines may have diagnostic potential in the work-up of patients with iNPH.

Few studies have investigated the measurement error of the Mini-Mental State Examination (MMSE) in the same unit of measurement, also known as absolute reliability. This measurement can help determine whether an observed score change for an individual is likely to represent true change. The aim of this study was to investigate the absolute reliability of the MMSE among individuals with dementia that reside in nursing homes. Among 88 participants, 19 (21.6%) were men, 35 (39.8%) had Alzheimer’s disease, 35 (39.8%) had vascular dementia, and the mean age was 84.0 years (range 65–98). The participants were tested and retested with the MMSE within 1–6 days. Both tests were administered by the same assessor at the same time of day. The mean MMSE score was 13.7 (range 0–28). The absolute difference between MMSE scores varied from 0 to 6 points, and the differences did not correlate with the corresponding score means (p = 0.874). The smallest detectable change (SDC) between two measurements was 4.00. The SDC was independent of depression, impaired vision and hearing, delirium within the last week, dementia type and age. However, the SDC was 5.56 among men and 3.50 among women (p = 0.003). In conclusion, for individuals with dementia that reside in nursing homes, it seems like their MMSE score needs to change by four or more points between two measurements in order for their score change to be reliably higher than the measurement error.