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The objectives of this study were to explore the relationship between olfactory impairment, cognitive measures, and brain structure volumes in healthy elderly individuals, compared to patients with amnestic mild cognitive impairment (aMCI) or early Alzheimer's disease (AD). The primary aim was to elucidate possible differences in cognitive scores and brain structure volumes between aMCI/AD patients with relatively intact odor identification (OI) ability and those with reduced ability.
Depression and depressive symptoms are highly prevalent in old persons but are potentially reversible. Full recovery is the main goal in the treatment of depressive episodes. Compared to clinical trials, observational studies of patients with depression in late life (DLL) show poorer prognoses in terms of response and remission. However, observational studies on the course of DLL are scarce. The aims of this study were to examine the course of DLL in terms of response, remission and symptom-specific changes as measured by the Montgomery and Asberg Depression Rating Scale (MADRS), and to explore which clinical variables were associated with the response and remission.
There has been increasing interest in the use of non-pharmacological interventions, such as physical exercise, to improve the well-being of nursing home residents with dementia. For reasons regarding disease symptoms, persons with dementia might find it difficult to participate in exercise programs. Therefore, it is important to find ways to successfully promote regular exercise for patients in residential care. Several quantitative studies have established the positive effects of exercise on biopsychosocial factors, such as self-efficacy in older people; however, little is known regarding the qualitative aspects of participating in an exercise program among older people with dementia. From the perspective of residents, we explored the experiences of participating in a high-intensity functional exercise program among nursing home residents with dementia.
Objective: Late-life depression (LLD) is associated with development of different types of dementia. Identification of LLD patients, who will develop cognitive decline, i.e., the early stage of dementia would help to implement interventions earlier. The purpose of this study was to assess whether structural brain magnetic resonance imaging (MRI) in LLD patients can predict mild cognitive impairment (MCI) or dementia 1 year prior to the diagnosis. Methods: LLD patients underwent brain MRI at baseline and repeated clinical assessment after 1-year. Structural brain measurements were obtained using Freesurfer software (v. 5.1) from the T1W brain MRI images. MRI-based Random Forest classifier was used to discriminate between LLD who developed MCI or dementia after 1-year follow-up and cognitively stable LLD. Additionally, a previously established Random Forest model trained on 185 patients with Alzheimer's disease (AD) vs. 225 cognitively normal elderly from the Alzheimer's disease Neuroimaging Initiative was tested on the LLD data set (ADNI model). Results: MCI and dementia diagnoses were predicted in LLD patients with 76%/68%/84% accuracy/sensitivity/specificity. Adding the baseline Mini-Mental State Examination (MMSE) scores to the models improved accuracy/sensitivity/specificity to 81%/75%/86%. The best model predicted MCI status alone using MRI and baseline MMSE scores with accuracy/sensitivity/specificity of 89%/85%/90%. The most important region for all the models was right ventral diencephalon, including hypothalamus. Its volume correlated negatively with the number of depressive episodes. ADNI model trained on AD vs. Controls using SV could predict MCI-DEM patients with 67% accuracy. Conclusion: LDD patients developing MCI and dementia can be discriminated from LLD patients remaining cognitively stable with good accuracy based on baseline structural MRI alone. Baseline MMSE score improves prediction accuracy. Ventral diencephalon, including the hypothalamus might play an important role in preservation of cognitive functions in LLD.
Little is known about factors associated with alcohol consumption and use of drugs with addiction potential in older adults. The aim of this study was to explore the association between socio-demographic variables, physical and mental health and the later (11 years) use of frequent drinking, prescribed drugs with addiction potential and the possible combination of frequent drinking and being prescribed drugs with addiction potential in older adults (≥ 65 years).
Alzheimer's disease (AD) is a debilitating age-related neurodegenerative disorder. Accurate identification of individuals at risk is complicated as AD shares cognitive and brain features with aging. We applied linked independent component analysis (LICA) on three complementary measures of gray matter structure: cortical thickness, area and gray matter density of 137 AD, 78 mild (MCI) and 38 subjective cognitive impairment patients, and 355 healthy adults aged 18-78 years to identify dissociable multivariate morphological patterns sensitive to age and diagnosis. Using the lasso classifier, we performed group classification and prediction of cognition and age at different age ranges to assess the sensitivity and diagnostic accuracy of the LICA patterns in relation to AD, as well as early and late healthy aging. Three components showed high sensitivity to the diagnosis and cognitive status of AD, with different relationships with age: one reflected an anterior-posterior gradient in thickness and gray matter density and was uniquely related to diagnosis, whereas the other two, reflecting widespread cortical thickness and medial temporal lobe volume, respectively, also correlated significantly with age. Repeating the LICA decomposition and between-subject analysis on ADNI data, including 186 AD, 395 MCI and 220 age-matched healthy controls, revealed largely consistent brain patterns and clinical associations across samples. Classification results showed that multivariate LICA-derived brain characteristics could be used to predict AD and age with high accuracy (area under ROC curve up to 0.93 for classification of AD from controls). Comparison between classifiers based on feature ranking and feature selection suggests both common and unique feature sets implicated in AD and aging, and provides evidence of distinct age-related differences in early compared to late aging.
Little is known about the consumption habits of older adults in Norway with respect to alcohol and the use of drugs with addiction potential, such as benzodiazepines, z-hypnotics and opioids, among regular drinkers. We studied the prevalence of self-reported consumption of alcohol on a regular basis in community-living older men and women (≥ 65 years). Furthermore, we investigated the prevalence of dispensed prescribed drugs with addiction potential in older men and women who were regular drinkers.
Large-scale brain networks are disrupted in the early stages of Alzheimer's disease (AD). Electroencephalography microstate analysis, a promising method for studying brain networks, parses EEG signals into topographies representing discrete, sequential network activations. Prior studies indicate that patients with AD show a pattern of global microstate disorganization. We investigated whether any specific microstate changes could be found in patients with AD and mild cognitive impairment (MCI) compared to healthy controls (HC).
Treatment of hypertension post-stroke preserves cognition through prevention of recurrent stroke, but it is not clear whether it prevents cognitive decline through other mechanisms. We aimed to describe changes in blood pressure from baseline to 1 year post-stroke and to evaluate the association between achieved blood pressure targets and cognitive function, mild cognitive impairment (MCI), and dementia.
The cerebrospinal fluid (CSF) biomarkers amyloid β (Aβ), phospho tau (P-tau) and total tau (T-tau) are used increasingly to support a clinical diagnosis of Alzheimer's disease. The diagnostic power of these biomarkers has been reported to vary among different studies' results. The results are poorer when heterogeneous groups of patients have been included compared to studies where patients with Alzheimer's dementia (AD) and healthy controls have been studied. The aim of this study was to examine if age, APOE genotype and sex were associated with the levels of CSF biomarkers among patients referred to a memory clinic.
Recent efforts using diffusion tensor imaging (DTI) have documented white matter (WM) alterations in Alzheimer's disease (AD). The full potential of whole-brain DTI, however, has not been fully exploited as studies have focused on individual microstructural indices independently. In patients with AD (n = 79), mild (MCI, n = 55) and subjective (SCI, n = 30) cognitive impairment, we applied linked independent component analysis (LICA) to model inter-subject variability across five complementary DTI measures (fractional anisotropy (FA), axial/radial/mean diffusivity, diffusion tensor mode), two crossing fiber measures estimated using a multi-compartment crossing-fiber model reflecting the volume fraction of the dominant (f1) and non-dominant (f2) diffusion orientation, and finally, connectivity density obtained from full-brain probabilistic tractography. The LICA component explaining the largest data variance was highly sensitive to disease severity (AD < MCI < SCI) and revealed widespread coordinated decreases in FA and f1 with increases in all diffusivity measures in AD. Additionally, it reflected regional coordinated decreases and increases in f2, mode and connectivity density, implicating bidirectional alterations of crossing fibers in the fornix, uncinate fasciculi, corpus callosum and major sensorimotor pathways. LICA yielded improved diagnostic classification performance compared to univariate region-of-interest features. Our results document coordinated WM microstructural and connectivity alterations in line with disease severity across the AD continuum.
The Liverpool Care Pathway (LCP) is an interdisciplinary protocol, aiming to ensure that dying patients receive dignified and individualized treatment and care at the end-of-life. LCP was originally developed in 1997 in the United Kingdom from a model of cancer care successfully established in hospices. It has since been introduced in many countries, including Norway. The method was withdrawn in the UK in 2013. This review investigates whether LCP has been adapted and validated for use in nursing homes and for dying people with dementia.
MRI assessment of the brain has demonstrated four different patterns of atrophy in patients with Alzheimer's disease dementia (AD): typical AD, limbic-predominant AD, hippocampal-sparing AD, and a subtype with minimal atrophy, previously referred to as no-atrophy AD. The aim of the present study was to identify and describe the differences between these four AD subtypes in a longitudinal memory-clinic study.
The prevalence of major depression (MD) according to population studies is the same for old (65 years and older) and younger adults. In contrast, an elevated proportion of old MD patients are hospitalized compared to younger adults with MD, indicating a need to expand the characteristics of old inpatients with MD. To illustrate this point, the association between inflammation and MD in old psychiatric inpatients is sparsely investigated even though an association between inflammation and treatment resistance among younger adults with MD has been reported. In this study, we aimed to explore the plasma concentrations of 27 immune markers in old inpatients with MD, and our purpose was to expand the understanding of inflammatory mechanisms in these patients.
Delirium is common in hip fracture patients and many risk factors have been identified. Controversy exists regarding the possible impact of intraoperative control of blood pressure upon acute (delirium) and long term (dementia) cognitive decline. We explored possible associations between perioperative hemodynamic changes, use of vasopressor drugs, risk of delirium and risk of new-onset dementia.
Few randomized clinical trials have explored the health effects of bilberries in humans. The aim was to test the effect of bilberry and red grape-juice consumption on visual memory, motor speed and dexterity as well as inflammatory and tissue damage biomarkers of plasma in aged men with subjective memory impairment.
A large fraction of genetic risk factors for Alzheimer's Disease (AD) is still not identified, limiting the understanding of AD pathology and study of therapeutic targets. We conducted a genome-wide association study (GWAS) of AD cases and controls of European descent from the multi-center DemGene network across Norway and two independent European cohorts. In a two-stage process, we first performed a meta-analysis using GWAS results from 2,893 AD cases and 6,858 cognitively normal controls from Norway and 25,580 cases and 48,466 controls from the International Genomics of Alzheimer's Project (IGAP), denoted the discovery sample. Second, we selected the top hits (p < 1 × 10-6) from the discovery analysis for replication in an Icelandic cohort consisting of 5,341 cases and 110,008 controls. We identified a novel genomic region with genome-wide significant association with AD on chromosome 4 (combined analysis OR = 1.07, p = 2.48 x 10-8). This finding implicated HS3ST1, a gene expressed throughout the brain particularly in the cerebellar cortex. In addition, we identified IGHV1-68 in the discovery sample, previously not associated with AD. We also associated USP6NL/ECHDC3 and BZRAP1-AS1 to AD, confirming findings from a follow-up transethnic study. These new gene loci provide further evidence for AD as a polygenic disorder, and suggest new mechanistic pathways that warrant further investigation.
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