0000000000116847
AUTHOR
Hilkka Soininen
Harmonized benchmark labels of the hippocampus on magnetic resonance: The EADC-ADNI project
Abstract Background A globally harmonized protocol (HarP) for manual hippocampal segmentation based on magnetic resonance has been recently developed by a task force from European Alzheimer's Disease Consortium (EADC) and Alzheimer's Disease Neuroimaging Initiative (ADNI). Our aim was to produce benchmark labels based on the HarP for manual segmentation. Methods Five experts of manual hippocampal segmentation underwent specific training on the HarP and segmented 40 right and left hippocampi from 10 ADNI subjects on both 1.5 T and 3 T scans. An independent expert visually checked segmentations for compliance with the HarP. Descriptive measures of agreement between tracers were intraclass cor…
Association between mid- to late life physical fitness and dementia: Evidence from the CAIDE study
Objectives. This study investigated the association between perceived physical fitness at midlife, changes in perceived fitness during the three decades from mid-to late life and dementia risk. Design. Prospective cohort study. Setting. Cardiovascular risk factors, ageing and incidence of dementia (CAIDE) study. Subjects. Subjects were selected from four independent, random samples of population-based cardiovascular surveys and were first examined in 1972, 1977, 1982 or 1987, when they were on average 50 years old. The CAIDE target population included 3559 individuals. A random sample of 2000 individuals still alive in 1997 was drawn for re-examinations (performed in 1998 and 2005-2008) tha…
Leisure-time physical activity from mid- to late life, body mass index, and risk of dementia
Abstract Background Physical activity may be beneficial for cognition, but the effect may vary depending on personal characteristics. Methods We investigated the associations between leisure-time physical activity (LTPA) from mid- to late life, the risk of dementia, and the role of body mass index, sex, and APOE in the CAIDE study during 28-year follow-up. Cognitive function of a random subsample was assessed at a mean age of 78.8 years (n = 1511), and dementia/Alzheimer's disease (AD) diagnoses were identified from national registers for the entire target population (n = 3559). Results Moderate (hazard ratio [HR], 1.46; 95% confidence interval [CI], 1.08–1.99) and low levels of midlife LTP…
Epilepsy in neuropathologically verified Alzheimer's disease
Purpose Subjects with Alzheimer’s disease (AD) have been shown to be at a higher risk for epilepsy. The vast majority of the previous studies have not included a full neuropathological examination. Methods The objective of this study was to assess the prevalence of epilepsy and clinicopathological characteristics in a well-defined study group of 64 subjects with AD. We evaluated the clinicopathological findings in 64 subjects (mean age at death 85 ± 8.6 years) from a longitudi-nal study cohort of patients with dementia. Results Eleven out of the 64 subjects (17%) had a history of epilepsy, which is comparable to previous studies. The subjects with AD and epilepsy were significantly younger …
Epilepsy in neuropathologically verified Alzheimer's disease.
Abstract Purpose Subjects with Alzheimer's disease (AD) have been shown to be at a higher risk for epilepsy. The vast majority of the previous studies have not included a full neuropathological examination. Methods The objective of this study was to assess the prevalence of epilepsy and clinicopathological characteristics in a well-defined study group of 64 subjects with AD. We evaluated the clinicopathological findings in 64 subjects (mean age at death 85 ± 8.6 years) from a longitudi-nal study cohort of patients with dementia. Results Eleven out of the 64 subjects (17%) had a history of epilepsy, which is comparable to previous studies. The subjects with AD and epilepsy were significantly…
Long-Term Response to Cholinesterase Inhibitor Treatment Is Related to Functional MRI Response in Alzheimer's Disease.
<b><i>Background:</i></b> Treatment of Alzheimer's disease (AD) with cholinesterase inhibitors (ChEI) enhances cholinergic activity and alleviates clinical symptoms. However, there is variation in the clinical response as well as system level changes revealed by functional MRI (fMRI) studies. <b><i>Methods:</i></b> We investigated 18 newly diagnosed mild AD patients with fMRI using a face recognition task after a single oral dose of rivastigmine, a single dose of placebo and 1-month treatment with rivastigmine. The clinical follow-up took place at 6 and 12 months. <b><i>Results:</i></b> MMSE score difference between bas…
P3‐315: MID‐LIFE WORK‐RELATED STRESS INCREASES DEMENTIA RISK IN LATE‐LIFE: THE CAIDE 30‐YEAR STUDY
Background: The associations between work-related stress and various health outcomes in mid-life are well documented, yet less is known about the effects on late-life cognitive process and dementia. The current study investigated the associations between work-related stress in mid-life and the development of cognitive impairment and Alzheimer’s disease in late-life. Methods: The data was derived from the Cardiovascular Risk Factors, Aging, and Incidence of Dementia (CAIDE) study; a prospective cohort study. Participants were randomly selected from four independent population-based samples that completed cardiovascular surveys. First baseline examinations occurred when participants were 50 y…
CERAD neuropsychological battery total score in multinational mild cognitive impairment and control populations: the AddNeuroMed study.
An important focus in Alzheimer's disease (AD) research is the development of methods for early diagnosis. Despite progress with some other biomarkers, sensitive and specific neuropsychological measures for identifying subjects in the prodromal phase of AD remain the most promising early diagnostic tool. We evaluated the value of the composite score for the Consortium to Establish a Registry for Alzheimer's disease Neuropsychological Battery (CERAD-NB) in Europeans with mild cognitive impairment (MCI) and in control populations. Baseline clinical data were analyzed from 223 healthy elderly and 224 subjects with MCI from the prospective AddNeuroMed study carried out in Finland, France, Greec…
P2‐310: MIDLIFE SELF‐RATED HEALTH AND FITNESS IN RELATION TO WHITE MATTER LESIONS AND GREY MATTER VOLUME 20 YEARS LATER
Midlife self-rated health and fitness in relation to white matter lesions and grey matter volume 20 years later
Rare coding variants in PLCG2, ABI3, and TREM2 implicate microglial-mediated innate immunity in Alzheimer's disease
International audience; We identified rare coding variants associated with Alzheimer's disease in a three-stage case-control study of 85,133 subjects. In stage 1, we genotyped 34,174 samples using a whole-exome microarray. In stage 2, we tested associated variants (P < 1 × 10-4) in 35,962 independent samples using de novo genotyping and imputed genotypes. In stage 3, we used an additional 14,997 samples to test the most significant stage 2 associations (P < 5 × 10-8) using imputed genotypes. We observed three new genome-wide significant nonsynonymous variants associated with Alzheimer's disease: a protective variant in PLCG2 (rs72824905: p.Pro522Arg, P = 5.38 × 10-10, odds ratio (OR) = 0.68…
Effect of cholinergic stimulation in early Alzheimer's disease - functional imaging during a recognition memory task.
Treatment of Alzheimer's disease (AD) with acetylcholinesterase inhibitors (AChEI) enhances cholinergic activity and alleviates clinical symptoms. In the present functional magnetic resonance imaging (fMRI) study, we investigated the effect of the AChEI rivastigmine on cognitive function and brain activation patterns during a face recognition memory task. Twenty patients with newly-diagnosed mild AD were administered a single oral dose of placebo, a single dose of rivastigmine (acute), and twice-daily treatment with rivastigmine for 4 weeks (chronic). After each treatment, the patients underwent a facial recognition task during fMRI. The prefrontal areas known to be involved in face recogni…
The EADC-ADNI Harmonized Protocol for manual hippocampal segmentation on magnetic resonance : Evidence of validity
BackgroundAn international Delphi panel has defined a harmonized protocol (HarP) for the manual segmentation of the hippocampus on MR. The aim of this study is to study the concurrent validity of the HarP toward local protocols, and its major sources of variance.MethodsFourteen tracers segmented 10 Alzheimer's Disease Neuroimaging Initiative (ADNI) cases scanned at 1.5 T and 3T following local protocols, qualified for segmentation based on the HarP through a standard web-platform and resegmented following the HarP. The five most accurate tracers followed the HarP to segment 15 ADNI cases acquired at three time points on both 1.5 T and 3T.ResultsThe agreement among tracers was relatively low…
Differential Associations of IL-4 With Hippocampal Subfields in Mild Cognitive Impairment and Alzheimer’s Disease
Background/Aims: A bi-directional communication between the immune system and the central nervous system has been recently suggested. Among many cytokines, the role of IL-4 - with anti-inflammatory properties- in counteracting age-related inflammatory changes in the brain is strongly supported among studies. With this study, we aimed at investigating the association between volumetric measures of hippocampal subregions -in healthy older controls (HC), subjects affected by mild cognitive impairment (MCI) and Alzheimer’s Disease (AD)- with circulating levels of IL-4. Methods: From AddNeuroMed Project 113 HC, 101 stable MCI (sMCI), 22 converter MCI (cMCI) and 119 AD were included. Hippocampal …
Down-Regulation of Ku Autoantigen, DNA-Dependent Protein Kinase, and Poly(ADP-ribose) Polymerase during Cellular Senescence
During aging and cellular senescence mutations accumulate in genomic and mitochondrial DNA. Ku autoantigens, DNA-dependent protein kinase, and poly (ADP-ribose) polymerase have an essential role in DNA damage recognition. Our purpose was to find out whether cellular senescence of fibroblasts affects the protein components that recognize DNA damage and induce the repair process. We compared presenescent and replicatively senescent human WI-38 fibroblasts with each other and with SV-40 immortalized and serum-deficient quiescent WI-38 cells. Our results showed that replicative senescence significantly decreased the nuclear level of both p70 and p86 components of Ku autoantigen. SV-40 immortali…