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Biomedical subjects

Steffi Riedel-Heller

Publications and source records attributed to Steffi Riedel-Heller.

7 recordsLinked to original sources
PubMed2026

APOE-stratified genome-wide association analyses provide insights into the genetic etiology of Alzheimers's disease.

Among the more than 90 identified genetic risk loci for late-onset Alzheimer's disease (AD) and related dementias, the apolipoprotein E (APOE) gene ɛ2/ɛ3/ɛ4 polymorphisms remain the longstanding benchmark for genetic disease risk with a consistently large effect across studies1-10. Despite this massive signal, the exact mechanisms by which ɛ4 increases and ɛ2 decreases dementia risk remain poorly understood. Notably, recent trials of anti-amyloid therapies suggest less efficacy and higher risks of severe side effects in ε4 carriers11-13, hampering the treatment of those with the highest unmet need. To improve our understanding of the genetic architecture of AD in the context of its main genetic driver, we performed genome-wide association studies (GWASs) stratified by ε4 and ε2 carrier status. HP1BP3, SLC50A1, PTPRC, NPAS3, DDHD1, CHST9, SMYD2, PRAMEF1 and GFRA1 emerged as new genomic signals for AD risk, appearing only when stratified by APOE carrier status. DDHD1 appeared especially promising, showing protective effects in ε4 carriers, being identified as an expression quantitative trait locus and being involved in rare neuronal diseases. Such APOE-stratified insights may help understand and overcome side effects, inform clinical trial enrollment strategies, and create the scientific basis for targeted, mechanism-driven therapies in neurodegenerative diseases.

Journal Article↗
PubMed2024

X-chromosome-wide association study for Alzheimer's disease.

Due to methodological reasons, the X-chromosome has not been featured in the major genome-wide association studies on Alzheimer's Disease (AD). To address this and better characterize the genetic landscape of AD, we performed an in-depth X-Chromosome-Wide Association Study (XWAS) in 115,841 AD cases or AD proxy cases, including 52,214 clinically-diagnosed AD cases, and 613,671 controls. We considered three approaches to account for the different X-chromosome inactivation (XCI) states in females, i.e. random XCI, skewed XCI, and escape XCI. We did not detect any genome-wide significant signals (P ≤ 5 × 10-8) but identified seven X-chromosome-wide significant loci (P ≤ 1.6 × 10-6). The index variants were common for the Xp22.32, FRMPD4, DMD and Xq25 loci, and rare for the WNK3, PJA1, and DACH2 loci. Overall, this well-powered XWAS found no genetic risk factors for AD on the non-pseudoautosomal region of the X-chromosome, but it identified suggestive signals warranting further investigations.

Humans↗
PubMed2006

Is mortality increased in mildly cognitively impaired individuals? A systematic literature review.

Numerous studies have focused on the effect of mild cognitive impairment in elderly people. However, the impact of mild cognitive impairment on mortality has rarely been considered so far. This paper reviews recent work on mild cognitive impairment and its mortality risk. Relevant articles were identified by a systematic search of the literature published since 1990 using the databases PubMed, Web of Science and PSYNDEXplus, bibliographies of articles identified and of earlier reviews. Those studies were considered which predominantly included persons aged 65 and over and which relied on population-based samples. Thus only eight studies could be identified. In general, the relative risk (RR) for subjects with mild cognitive impairment according to different concepts in comparison to non-affected persons varies from 1.0 to 1.9. However, only few studies are available, and a comparison of the literature is problematic, due to variations in criteria and methodology.

Aged↗
PubMed2005

Morphometry of the amygdala in patients with questionable dementia and mild dementia.

The volume of the amygdala is reduced in advanced Alzheimer's disease (AD). However, there is controversy whether amygdala atrophy is present in mild AD and in the transitional phase between health and the onset of dementia. The aim of this prospective longitudinal study was to investigate whether amygdala atrophy is present in subjects with questionable dementia and mild dementia and whether amygdala volume is associated with the future rate of cognitive change, that is the annual change in the Mini Mental State Examination (MMSE). At baseline, volumes of the amygdala were measured in 97 participants aged 70-87 years (40 controls, 33 patients with questionable dementia, 24 patients with mild AD) using magnetic resonance imaging. Eighty-six participants were clinically re-examined after 2.3 years on average. At baseline, significant differences in mean amygdala volume were found between controls and participants with mild AD. There was no significant correlation between the longitudinal annual change in MMSE and the baseline amygdala volume in any of the three groups.

Aged↗
PubMed2005

Mortality in dementia.

The objective of this work is to provide a review of the mortality risk in dementia and potential influencing factors. In order to do so, studies on mortality in dementia based on population-based samples of the last 15 years published in PubMed, Web of Science and PSYNDEXplus were considered. Without exception, all types of dementia are associated with a considerably increased mortality risk. Moreover, the risk of death rises with advancing severity of the disorder. Often, a more favorable course of the disease can be found in Alzheimer's disease. Further questions, such as the influence of age and sex, cannot be answered conclusively. Very little information can be found on aspects concerning comorbidity, APOE polymorphism or depressive symptomatology.

Age Factors↗
PubMedDate not supplied

Theta-power differences in patients with mild cognitive impairment under rest condition and during haptic tasks.

The aim of this study was to investigate spectral EEG theta-power during perceptive-cognitive demands in age-homogeneous groups of subjects with mild cognitive impairment (MCI), mild dementia (MDE), and a healthy control (CO) group. The present study includes 51 subjects (23 males, 28 females). We used the scales of the CDR (clinical dementia rating) to assign the subjects to the different groups. EEG data were collected during 10 minutes rest condition with eyes closed and during haptic perception test. The quality of the haptic reproductions differed significantly between CO and MCI, as well as between CO and MDE. The statistical comparison between EEG theta-power under rest condition and theta-power during haptic tasks revealed a significant decrease in theta-power during haptic tasks in all three groups over parieto-occipital regions. During haptic tasks, the theta-power was significantly different between CO and MDE over occipital regions and over parieto-temporal regions. A significant difference between CO and MCI was only revealed over right occipital regions (O2). Spectral theta-power during haptic tasks is a suitable measure to distinguish healthy subjects (CO) from patients with MCI respectively MDE. The results show that haptic tasks are sensitive to early perceptive-cognitive and functional deficits in patients with MCI.

Aged↗