O3-05-03: Relation between Alzheimer's genetic risk factors and long-term memory decline in nondemented subjects with cognitive impairments

There was some recent progress in the understanding of genetic risk factors in chronic pancreatitis. Due to this progress some of the traditional views of the subject will change. Today, genetic risk factors are attributed a much more important role that in the past. The frequency and strength of mutations were higher than expected. Strong variants were the rare autosomal-dominant mutations N29I and R122H of PRSS1 (cationic trypsinogen) and homozygous N34S of SPINK1 (pancreatic secretory trypsin inhibitor). Other mutations (heterozygous N34S, CFTR) were of lower relevance but still mediate a higher risk than alcohol consumption. The course of genetically determined pancreatitis is rather mild. In the long term pancreas cancer was found in some patients but apart from non-smoking no adequate prophylactic strategy is available up to now.

Download Full-text

Cognitive Reserve, Incident Cancer, and Rate of Memory Decline in Later Life

Innovation in Aging ◽

10.1093/geroni/igaa057.477 ◽

2020 ◽

Vol 4 (Supplement_1) ◽

pp. 146-146

Author(s):

Monica Ospina Romero ◽

Willa Brenowitz ◽

Eleanor Hayes-Larson ◽

Sarah F Ackley ◽

Elizabeth R Mayeda ◽

...

Keyword(s):

Cognitive Decline ◽

Cancer Diagnosis ◽

Cognitive Reserve ◽

Word Recall ◽

Long Term Memory ◽

Memory Decline ◽

Term Memory ◽

Incident Cancer ◽

After Cancer

Abstract Cognitive reserve (cognitive skills and abilities acquired before onset of brain pathology) helps maintain cognitive function during aging. Cognitive decline after cancer treatment, known as “chemobrain,” is a prevalent outcome among older cancer survivors. It is unknown whether cognitive reserve buffers against acute neuropathological events such as cancer-related cognitive decline. We examined acute and long-term rate of memory decline associated with incident cancer diagnosis by education levels as proxy for cognitive reserve (low: <12 years; intermediate: 12 to <16 years; high: ≥16 years) in 14,449 adults aged 50+ in the US Health and Retirement Study from 1998-2016. Memory (z-scored) was assessed biennially as immediate and delayed word recall combined with proxy assessments. We used adjusted linear mixed models to determine long-term rates of memory decline before and after cancer diagnosis, and acute memory decline immediately after diagnosis (3,248 incident cases), and compared them with corresponding memory trajectories in cancer-free participants. Acute memory decline immediately after diagnosis was larger in those with low (-0.098 SD units, 95% CI: -0.150, -0.045) versus high (-0.038 SD units, 95% CI: -0.084, -0.008) education. Long-term memory decline after cancer was faster in those with low (-1.16 SD units/decade, 95% CI: -1.25, -1.07) versus high (-0.89 SD units/decade, 95% CI: -0.96, -0.82) education. Consistent with previous research showing an inverse cancer-dementia relationship, individuals with cancer had more favorable memory trajectories than cancer-free individuals with similar age and education. Among those with cancer, lower cognitive reserve was associated with greater acute and long-term memory decline after diagnosis.

Download Full-text

Similar Profile and Magnitude of Cognitive Impairments in Focal and Generalized Epilepsy: A Pilot Study

Frontiers in Neurology ◽

10.3389/fneur.2021.746381 ◽

2022 ◽

Vol 12 ◽

Author(s):

Helena Gauffin ◽

Anne-Marie Landtblom ◽

Patrick Vigren ◽

Andreas Frick ◽

Maria Engström ◽

...

Keyword(s):

Quality Of Life ◽

Cognitive Function ◽

Focal Epilepsy ◽

Cognitive Impairments ◽

Self Esteem ◽

Long Term Memory ◽

Term Memory ◽

Generalized Epilepsy

Introduction: Cognitive impairments in epilepsy are not well-understood. In addition, long-term emotional, interpersonal, and social consequences of the underlying disturbances are important to evaluate.Purpose: To compare cognitive function including language in young adults with focal or generalized epilepsy. In addition, quality of life and self-esteem were investigated.Patients and Methods: Young adults with no primary intellectual disability, 17 with focal epilepsy and 11 with generalized epilepsy participated and were compared to 28 healthy controls. Groups were matched on age (mean = 26 years), sex, and education. Participants were administered a battery of neuropsychological tasks and carried out self-ratings of quality of life, self-esteem, and psychological problems.Results: Similar impairments regarding cognitive function were noted in focal and generalized epilepsy. The cognitive domains tested were episodic long-term memory, executive functions, attention, working memory, visuospatial functions, and language. Both epilepsy groups had lower results compared to controls (effect sizes 0.24–1.07). The total number of convulsive seizures was predictive of episodic long-term memory function. Participants with focal epilepsy reported lower quality of life than participants with generalized epilepsy. Lowered self-esteem values were seen in both epilepsy groups and particularly in those with focal epilepsy. Along with measures of cognitive speed and depression, the total number of seizures explained more than 50% of variation in quality of life.Conclusion: Interestingly, similarities rather than differences characterized the widespread cognitive deficits that were seen in focal and generalized epilepsy, ranging from mild to moderate. These similarities were modified by quality of life and self-esteem. This study confirms the notion that epilepsy is a network disorder.

Download Full-text

Hippocampal interleukin-33 mediates neuroinflammation induced cognitive impairments

10.21203/rs.3.rs-20583/v1 ◽

2020 ◽

Author(s):

Flora Reverchon ◽

Vidian de Concini ◽

Vanessa Larrigaldie ◽

Sulayman Benmerzoug ◽

Dieudonnée Togbé ◽

...

Keyword(s):

Cell Sorting ◽

Cell Activation ◽

Inflammatory Responses ◽

Cognitive Impairments ◽

Cognitive Disorders ◽

Long Term Memory ◽

Fluorescence Activated Cell Sorting ◽

Term Memory ◽

Deficient Mice

Abstract BackgroundInterleukin (IL)-33 is expressed in healthy brain and plays a pivotal role in several neuropathologies, as protective or contributing to the development of cerebral diseases associated with cognitive impairments. However, the role of IL-33 in the brain is poorly understood, raising the question of its involvement in immunoregulatory mechanisms.MethodsWe induced a local IL-33 release by intra-hippocampal injection of recombinant mouse IL-33 (rmIL-33) into C57BL/6J (WT) and IL-1ab deficient mice. Chronic minocycline administration was done and cognitive functions were examined trough short- and long-term memory assays. Hippocampal inflammatory responses were investigated by RT-qPCR. The microglia activation was assessed using immunohistological staining and Fluorescence-activated cell sorting. ResultsWe showed that IL-33 administration in mice led to a long-term memory defect associated with an increase of inflammatory markers in hippocampus while, minocycline administration limited the inflammatory response. Quantitative assessment of glial cell activation in situ was performed and demonstrated an increase of proximal intersections per radius in each part of hippocampus. Moreover, rmIL-33 significantly promoted the outgrowth of microglial processes. Fluorescence-activated cell sorting performed on isolated microglia, revealed an overexpression of IL-1β, 48h post-rmIL-33 administration. This microglial reactivity was closely related to the onset of cognitive disturbance. Finally, we demonstrated that IL-1ab deficient mice were resistant to cognitive disorders after intra-hippocampal IL-33 injection. ConclusionThus, hippocampal IL-33 induced an inflammatory state, including IL-1β overexpression by microglia cells, being causative of the cognitive impairment. These results highlight the pathological role for IL-33 in the central nervous system, independently of a specific neuropathological model.

Download Full-text