Publications by authors named "Willemijn J. Jansen"
Background: To aid development of prevention strategies, we investigated whether a composite measure of late‐midlife lifestyle health was associated with (1) change in brain tau burden, vascular burden and neurodegeneration and (2) cognitive trajectories when accounting for these brain changes.
Method: We included 324 individuals from the Wisconsin Registry for Alzheimer’s Prevention. Late‐midlife lifestyle was assessed using the Lifestyle for Brain Health (LIBRA) score, encompassing 12 risk‐and protective factors for cognitive decline and dementia.
Background: Amyloid‐b deposition and tau tangle formation are the key pathologies of Alzheimer’s disease (AD). The presence of these pathologies in cerebrospinal fluid (CSF) biomarkers is used for a biological diagnosis of AD. It remains unclear how the prevalence of AT biomarker profiles depends on apolipoprotein E (APOE) genotype.
View Article and Find Full Text PDFBackground: Type 2 diabetes and glucose metabolism have previously been linked to cognitive decline and higher risk of developing Alzheimer’s disease (AD) dementia. Yet, the relation of glucose metabolism with amyloid and tau pathology remains unclear. This knowledge will help understanding the importance of glucose regulation in relation to AD.
View Article and Find Full Text PDFBackground: The emergence of disease‐modifying drug therapies is expected to revolutionize the field of Alzheimer's disease (AD). Recent results from anti‐amyloid clinical trials highlight the importance of early identification and accurate risk‐stratification of individuals in early stages of the disease. In this context, the Amyloid Imaging to Prevent Alzheimer’s Disease (AMYPAD) Prognostic and Natural History Study (PNHS) was established, leveraging existing cohorts to alleviate the burden of recruiting de novo participants.
View Article and Find Full Text PDFBackground: As global populations age, both Alzheimer’s Disease (AD) and diabetes mellitus (DM) incidence are projected to increase tremendously over the coming 20‐30 years. Studies have found that having DM is associated with increased risk of developing AD dementia. It remains unclear however whether DM impacts underlying AD pathology.
View Article and Find Full Text PDFAlzheimer's disease (AD) is a multifactorial disease with both genetic and environmental factors contributing to its etiology. Previous evidence has implicated disturbed insulin signaling as a key mechanism that plays a role in both neurodegenerative diseases such as AD and comorbid somatic diseases such as diabetes mellitus type 2 (DM2). In this study, we analysed available genome-wide association studies (GWASs) of AD and somatic insulin-related diseases and conditions (SID), i.
View Article and Find Full Text PDFArticle Synopsis
- This study examined the link between plasma biomarkers indicating endothelial dysfunction and cognitive performance in a sample of 9,414 older adults from the Netherlands, aged 57 to 93 years.
- Researchers created a composite score from three specific biomarkers and assessed various cognitive functions like executive function and memory.
- Results indicated a small, consistent association between higher endothelial dysfunction scores and poorer cognitive performance, but no evidence suggested that these markers influenced cognitive decline over time.
Article Synopsis
- The study investigated the relationship between glucose metabolism and the development of tau pathology, a hallmark of Alzheimer's disease, in middle-aged adults without dementia.
- Researchers analyzed data from 288 participants, examining their fasting plasma glucose and insulin levels and later PET scans for amyloid-β and tau loads.
- Results showed that elevated plasma glucose correlated with increased tau load after 14 years, particularly in individuals who were not carriers of the APOE ε4 allele, while insulin levels and HOMA-IR did not show significant associations with either amyloid-β or tau.
Article Synopsis
- The study investigates the relationship between insulin resistance (IR)-related conditions, like type 2 diabetes and obesity, and neuropsychiatric disorders, highlighting the complexity of their co-occurrence as a public health issue.
- Researchers used genome-wide association studies (GWASs) with a large sample size to analyze genetic correlations between these conditions, identifying various genomic regions with significant local correlations.
- The findings suggest that these correlated regions are linked to important biological pathways, indicating potential targets for treatments and a need for an integrated approach to understanding and managing these interconnected health problems.
Article Synopsis
- * Results showed that impaired glucose metabolism and DM status correlated with higher tau biomarkers, but not with amyloid-β, suggesting a specific association with tau in certain population settings.
- * These findings highlight the importance of understanding the relationship between DM and AD biomarkers, which could improve diagnostics and treatment for both conditions.
Article Synopsis
- Alzheimer's disease and vascular issues commonly affect the elderly, but how they impact cognitive decline is still unclear.
- The study examined 227 patients from memory clinics for the combined effect of amyloid abnormalities and vascular burdens on cognitive decline, using various cognitive assessments and MRI data.
- Results indicated that those with both amyloid abnormalities and vascular issues showed greater cognitive decline, but amyloid abnormalities were the main predictor of decline, suggesting vascular burden has a lesser role.
Article Synopsis
- Perivascular spaces (PVS) and blood-brain barrier (BBB) disruption are significant factors in cerebral small vessel disease (cSVD) and neurodegenerative diseases, impacting cognitive function and waste clearance in the brain.
- Magnetic resonance imaging (MRI) is a noninvasive method that allows researchers to study PVS functionality and BBB integrity, using techniques like dynamic contrast-enhanced (DCE) MRI and arterial spin labeling (ASL).
- Recent clinical studies using these MRI techniques have provided insights into the relationships between PVS, BBB dysfunction, cSVD, and neurodegenerative disorders, especially Alzheimer’s disease, revealing both similarities and differences between these conditions.
Article Synopsis
- This study explored the relationship between locus coeruleus (LC) degeneration and small blood vessel disease in the brain using data from two large neuropathology studies.
- Researchers found that LC hypopigmentation was linked to higher odds of cerebral amyloid angiopathy (CAA) and arteriolosclerosis, indicating a connection between LC pathology and vascular issues, independent of Alzheimer's disease pathology.
- The findings suggest that degeneration of the LC may influence the pathways connecting vascular health to Alzheimer's disease, highlighting the need for further research on the LC-norepinephrine system in relation to brain health.
Article Synopsis
- Clinical research indicates a significant overlap between neuropsychiatric disorders and insulin resistance-related conditions like obesity and type 2 diabetes, affecting cognitive function.
- The review analyzed 18 studies from the UK Biobank, confirming that insulin resistance is associated with poorer cognitive performance, particularly in verbal and numerical reasoning and processing speed.
- Possible mechanisms for these associations include changes in immune response, brain health and connectivity, and the presence of other health issues.
Article Synopsis
- Type 2 diabetes mellitus (T2DM) is linked to various psychiatric and neurological disorders, and this study aimed to explore these associations in a large cohort of Danish citizens, while considering the order of diagnosis between T2DM and brain disorders.
- The research analyzed data from nearly 1.9 million individuals born between 1955 and 1984, revealing significant associations between T2DM and a range of disorders, especially eating disorders and schizophrenia in the psychiatric category, along with inflammatory brain diseases and epilepsy in the neurological category.
- Most associations were found to exist regardless of whether T2DM was diagnosed before or after the brain disorders, indicating a possible shared underlying cause between T2DM and these conditions, particularly
Article Synopsis
- Somatic insulinopathies, including metabolic syndrome, obesity, and type 2 diabetes, are more prevalent in neuropsychiatric disorders like Alzheimer's disease, autism spectrum disorder, and obsessive-compulsive disorder.
- The study examined the genetic correlations between these disorders and insulin-related diseases using data from large genome-wide association studies, revealing significant negative correlations, particularly between OCD and metabolic syndrome, obesity, and type 2 diabetes.
- Further analysis indicated potential genetic clusters among various neuropsychiatric disorders, highlighting divergent relationships with insulin-related traits, suggesting a complex interplay between genetics and insulin signaling in these conditions.
Article Synopsis
- The study investigates the prevalence of amyloid aggregation, a key feature of Alzheimer's disease, in individuals with varying cognitive statuses, including those with normal cognition and who have clinical AD dementia.
- It analyzes how factors like age, sex, educational background, and the method of detecting amyloid (CSF or PET scans) influence the prevalence estimates.
- Data were collected from 85 study cohorts between 2013 and 2020, using a systematic approach to categorize amyloid measurements as normal or abnormal.
Article Synopsis
- There is limited evidence regarding the traits of individuals with subjective cognitive decline (SCD) who also have amyloid positivity, which is related to Alzheimer's disease.
- A study of 1640 participants showed that factors like age, clinical setting, and the presence of the APOE ε4 gene are linked to higher amyloid positivity, whereas education level also plays a role.
- Specific SCD characteristics such as confirmed complaints and lack of depressive symptoms were associated with amyloid positivity, suggesting these traits can aid in identifying individuals who may have amyloid-related cognitive decline.
Article Synopsis
- Advanced Alzheimer's disease (AD) shows increased levels of noradrenaline metabolites, indicating a potential link between these levels and AD pathology.
- The study examined 77 memory clinic patients, analyzing brain structure and fluid biomarkers to assess the relationship between noradrenaline turnover and brain morphology, focusing on the role of the locus coeruleus (LC).
- Results revealed that higher levels of the noradrenergic metabolite MHPG correlate with reduced cortical thickness and hippocampal volume, suggesting that these changes may occur early in the AD process, possibly aiding in early detection of the disease.
Article Synopsis
- * Our findings showed that Aβ levels affected several cognitive tests related to memory, attention, and executive function, especially as age increased, while tau had no significant influence.
- * We created Aβ-negative norms for memory tests, which successfully identified more individuals at risk for dementia compared to traditional norms, suggesting these new norms can enhance early dementia detection.
Article Synopsis
- - The study examined the prevalence of the APOE ε4 genetic risk factor for Alzheimer's disease (AD) in a group of 3451 individuals with confirmed amyloid β (Aβ) pathology, which had not been consistently used in earlier research.
- - Results showed that APOE ε4 prevalence was 66% in AD-type dementia, 64% in mild cognitive impairment, and 51% in cognitively normal individuals, with a notable decrease in prevalence as age increased among those who were cognitively normal or had mild cognitive impairment.
- - The findings indicated that the prevalence of APOE ε4 was higher than previously reported, underscoring significant differences in disease presentation based on age and geographic location, particularly being highest
Article Synopsis
- The study explores the link between amyloid-β aggregation, an early indicator of Alzheimer's disease, and cognitive functioning in individuals without dementia to improve our understanding of Alzheimer's progression and prevention strategies.
- It included a large sample of 7,041 participants, split between those with normal cognition and those with mild cognitive impairment, assessing cognitive performance and amyloid levels using various diagnostic tools.
- Findings revealed that amyloid positivity was significantly associated with lower memory scores, particularly in individuals over the age of 70, indicating a potential cognitive decline related to amyloid aggregation in older adults.
Article Synopsis
- A study of 413 individuals without initial cognitive impairment tracked their cognitive decline over an average of 10.4 years, ultimately correlating this decline with various dementia-related brain pathologies observed after death.
- The research found that while cognitive decline was gradual and then accelerated significantly in the last three years of life, specific brain abnormalities like neurofibrillary tangles and gross infarcts were linked to this decline.
- Importantly, the effects of these dementia-related pathologies on cognitive decline did not change significantly with age, indicating that the underlying causes of cognitive decline in older adults remain consistent regardless of age.
Article Synopsis
- The WFSBP has updated its 12-year-old consensus paper on biomarkers for neurodegenerative dementias, reflecting key advancements in understanding Alzheimer's disease and its diagnostic criteria.
- Improved procedures for handling and analyzing biological samples, along with global quality control projects, aim to standardize measurements across different research centers.
- Significant progress in neuroimaging and lab technologies promises better accuracy in diagnosing dementia, while new clinical trials assess the cost-effectiveness of biomarker-based diagnoses.