Deficient semantic knowledge of the life course—Examining the cultural life script in Alzheimer’s disease

AbstractBrain development and deterioration across the lifespan are integral to the etiology of late-life neurodegenerative disease. Factors that influence the health of the adult brain remain to be elucidated and include risk factors, protective factors, and factors related to cognitive and brain reserve. To address this knowledge gap we designed a life-course study on brain health, which received funding through the EU ERC Programme under the name Origins of Alzheimer’s Disease Across the Life course (ORACLE) Study. The ORACLE Study is embedded within Generation R, a prospective population-based cohort study of children and their parents, and links this with the Rotterdam Study, a population-based study in middle-aged and elderly persons. The studies are based in Rotterdam, the Netherlands. Generation R focuses on child health from fetal life until adolescence with repeated in-person examinations, but has also included data collection on the children’s parents. The ORACLE Study aims to extend the parental data collection in nearly 2000 parents with extensive measures on brain health, including neuroimaging, cognitive testing and motor testing. Additionally, questionnaires on migraine, depressive symptoms, sleep, and neurological family history were completed. These data allow for the investigation of longitudinal influences on adult brain health as well as intergenerational designs involving children and parents. As a secondary focus, the sampling is enriched by mothers (n = 356) that suffered from hypertensive disorders during pregnancy in order to study brain health in this high-risk population. This article provides an overview of the rationale and the design of the ORACLE Study.

Download Full-text

Gender and socioeconomic differences in modifiable risk factors for Alzheimer’s disease and other types of dementia throughout the life course

Sex and Gender Differences in Alzheimer's Disease ◽

10.1016/b978-0-12-819344-0.00004-1 ◽

2021 ◽

pp. 333-360

Author(s):

Stefania Ilinca ◽

Elina Suzuki

Keyword(s):

Risk Factors ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Life Course ◽

Modifiable Risk Factors ◽

Socioeconomic Differences ◽

The Life Course

Download Full-text

Using the life course perspective to study the entry into the illness trajectory: The perspective of caregivers of people with Alzheimer's disease

Social Science & Medicine ◽

10.1016/j.socscimed.2009.12.038 ◽

2010 ◽

Vol 70 (10) ◽

pp. 1501-1508 ◽

Cited By ~ 31

Author(s):

Normand Carpentier ◽

Paul Bernard ◽

Amanda Grenier ◽

Nancy Guberman

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Life Course ◽

Life Course Perspective ◽

Illness Trajectory ◽

The Life Course

Download Full-text

Life Course Adiposity and Alzheimer’s Disease: A Mendelian Randomization Study

Journal of Alzheimer s Disease ◽

10.3233/jad-210345 ◽

2021 ◽

pp. 1-10

Author(s):

Xian Li ◽

Yan Tian ◽

Yu-Xiang Yang ◽

Ya-Hui Ma ◽

Xue-Ning Shen ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Life Course ◽

Mendelian Randomization ◽

Association Studies ◽

Meta Analysis ◽

Genome Wide Association Studies ◽

Fat Percentage ◽

Regression Methods ◽

Weighted Median

Background: Several studies showed that life course adiposity was associated with Alzheimer’s disease (AD). However, the underlying causality remains unclear. Objective: We aimed to examine the causal relationship between life course adiposity and AD using Mendelian randomization (MR) analysis. Methods: Instrumental variants were obtained from large genome-wide association studies (GWAS) for life course adiposity, including birth weight (BW), childhood body mass index (BMI), adult BMI, waist circumference (WC), waist-to-hip ratio (WHR), and body fat percentage (BFP). A meta-analysis of GWAS for AD including 71,880 cases and 383,378 controls was used in this study. MR analyses were performed using inverse variance weighted (IVW), weighted median, and MR-Egger regression methods. We calculated odds ratios (ORs) per genetically predicted standard deviation (1-SD) unit increase in each trait for AD. Results: Genetically predicted 1-SD increase in adult BMI was significantly associated with higher risk of AD (IVW: OR = 1.03, 95% confidence interval [CI] = 1.01–1.05, p = 2.7×10–3) after Bonferroni correction. The weighted median method indicated a significant association between BW and AD (OR = 0.94, 95% CI = 0.90–0.98, p = 1.8×10–3). We also found suggestive associations of AD with WC (IVW: OR = 1.03, 95% CI = 1.00–1.07, p = 0.048) and WHR (weighted median: OR = 1.04, 95% CI = 1.00–1.07, p = 0.029). No association was detected of AD with childhood BMI and BFP. Conclusion: Our study demonstrated that lower BW and higher adult BMI had causal effects on increased AD risk.

Download Full-text

Anhedonia in Semantic Dementia—Exploring Right Hemispheric Contributions to the Loss of Pleasure

Brain Sciences ◽

10.3390/brainsci11080998 ◽

2021 ◽

Vol 11 (8) ◽

pp. 998

Author(s):

Siobhán R. Shaw ◽

Hashim El-Omar ◽

Siddharth Ramanan ◽

Olivier Piguet ◽

Rebekah M. Ahmed ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Temporal Lobe ◽

Rating Scale ◽

Right Hemisphere ◽

Semantic Knowledge ◽

Semantic Dementia ◽

Anterior Cingulate ◽

Functional Impairments ◽

Lobe Atrophy

Semantic dementia (SD) is a younger-onset neurodegenerative disease characterised by progressive deterioration of the semantic knowledge base in the context of predominantly left-lateralised anterior temporal lobe (ATL) atrophy. Mounting evidence indicates the emergence of florid socioemotional changes in SD as atrophy encroaches into right temporal regions. How lateralisation of temporal lobe pathology impacts the hedonic experience in SD remains largely unknown yet has important implications for understanding socioemotional and functional impairments in this syndrome. Here, we explored how lateralisation of temporal lobe atrophy impacts anhedonia severity on the Snaith–Hamilton Pleasure Scale in 28 SD patients presenting with variable right- (SD-R) and left-predominant (SD-L) profiles of temporal lobe atrophy compared to that of 30 participants with Alzheimer’s disease and 30 healthy older Control participants. Relative to Controls, SD-R but not SD-L or Alzheimer’s patients showed clinically significant anhedonia, representing a clear departure from premorbid levels. Overall, anhedonia was more strongly associated with functional impairment on the Frontotemporal Dementia Functional Rating Scale and motivational changes on the Cambridge Behavioural Inventory in SD than in Alzheimer’s disease patients. Voxel-based morphometry analyses revealed that anhedonia severity correlated with reduced grey matter intensity in a restricted set of regions centred on right orbitofrontal and temporopolar cortices, bilateral posterior temporal cortices, as well as the anterior cingulate gyrus and parahippocampal gyrus, bilaterally. Finally, regression and mediation analysis indicated a unique role for right temporal lobe structures in modulating anhedonia in SD. Our findings suggest that degeneration of predominantly right-hemisphere structures deleteriously impacts the capacity to experience pleasure in SD. These findings offer important insights into hemispheric lateralisation of motivational disturbances in dementia and suggest that anhedonia may emerge at different timescales in the SD disease trajectory depending on the integrity of the right hemisphere.

Download Full-text

Conceptual apraxia and semantic memory deficit in Alzheimer's disease: Two sides of the same coin?

Journal of the International Neuropsychological Society ◽

10.1017/s1355617700666079 ◽

2000 ◽

Vol 6 (6) ◽

pp. 693-703 ◽

Cited By ~ 33

Author(s):

CATHERINE DUMONT ◽

BERNADETTE SKA ◽

YVES JOANETTE

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Model ◽

Semantic Knowledge ◽

Matching Task ◽

Semantic Matching ◽

Language Deficit ◽

Sequential Organization ◽

Action Knowledge ◽

Actual Use

This study was designed to examine the patterns of apraxic disturbances and the relationships between action knowledge and other measures of semantic knowledge about objects in 10 well-characterized Alzheimer's disease (AD) patients. Five tasks were used to assess components of action knowledge (action–tool relationships, pantomime recognition, and sequential organization of action) and praxis execution (actual use, pantomiming) according to the cognitive model of praxis. Three tasks (verbal comprehension, naming, and a visual semantic matching task) were used to assess verbal–visual semantics. Considering patterns of apraxia first, conceptual apraxia was found in 9 out of the 10 AD patients, suggesting that it is a common feature even in the early stages of AD. Second, we found partly parallel deficits in tests of action-semantic and verbal–visual semantic knowledge in 9 AD patients. Impaired action knowledge was found only in patients with a semantic language deficit. These findings provide no evidence that “action semantics” may be separated from other semantic information. Our results support the view of a unitary semantic system, given that the representations of action-semantic and other semantic knowledge of objects are often simultaneously disrupted in AD. (JINS, 2000, 6, 693–703.)

Download Full-text

Semantic Processing in Healthy Aging and Alzheimer’s Disease: A Systematic Review of the N400 Differences

Brain Sciences ◽

10.3390/brainsci10110770 ◽

2020 ◽

Vol 10 (11) ◽

pp. 770

Author(s):

Marilyne Joyal ◽

Charles Groleau ◽

Clara Bouchard ◽

Maximiliano A. Wilson ◽

Shirley Fecteau

Keyword(s):

Systematic Review ◽

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Semantic Processing ◽

Healthy Aging ◽

Semantic Knowledge ◽

Event Related Potential ◽

N400 Effect ◽

Pathological Aging ◽

Healthy Elderly

Semantic deficits are common in individuals with Alzheimer’s disease (AD). These deficits notably impact the ability to understand words. In healthy aging, semantic knowledge increases but semantic processing (i.e., the ability to use this knowledge) may be impaired. This systematic review aimed to investigate semantic processing in healthy aging and AD through behavioral responses and the N400 brain event-related potential. The results of the quantitative and qualitative analyses suggested an overall decrease in accuracy and increase in response times in healthy elderly as compared to young adults, as well as in individuals with AD as compared to age-matched controls. The influence of semantic association, as measured by N400 effect amplitudes, appears smaller in healthy aging and even more so in AD patients. Thus, semantic processing differences may occur in both healthy and pathological aging. The establishment of norms of healthy aging for these outcomes that vary between normal and pathological aging could eventually help early detection of AD.

Download Full-text