NR Times explores the latest research developments in the world of neuro rehabilitation.
Four key pathways to Alzheimer’s disease mapped by researchers
Four distinct pathways that lead to Alzheimer’s disease have been identified by researchers, offering new insights into how the condition develops over time rather than from isolated risk factors.
The pathways were identified by analysing electronic health records, examining longitudinal health data from nearly 25,000 patients in the University of California Health Data Warehouse and validating the findings in the nationally diverse All of Us Research Program.
Unlike previous research that focused on individual risk factors, the UCLA analysis mapped sequential diagnostic patterns that revealed how conditions progress step-by-step toward Alzheimer’s disease.
The research identified four major trajectory clusters.
The first is a mental health pathway, characterized by psychiatric conditions leading to cognitive decline; the second is the encephalopathy pathway, with brain dysfunction conditions escalating over time; and the third is a mild cognitive impairment pathway characterized by gradual cognitive decline progression.
The fourth pathway is a vascular disease pathway whereby cardiovascular conditions contribute to dementia risk.
The researchers say that each pathway showed distinct demographic and clinical characteristics, suggesting that different populations may be vulnerable to different progression routes.
The study found that approximately 26 per cent of diagnostic progressions showed consistent directional ordering. For example, hypertension often preceded depressive episodes, which then increased Alzheimer’s risk.
When validated in an independent population, these multi-step trajectories predicted Alzheimer’s disease risk more accurately than single diagnoses alone.
This finding suggests that healthcare providers could use trajectory patterns for enhanced risk stratification, targeted interventions, and personalised prevention.
Intra-arterial tenecteplase for acute stroke after successful endovascular therapy
A new study has found that, in patients with acute large vessel occlusion presenting between 4.5 and 24 hours of symptom onset, intra-arterial tenecteplase after successful thrombectomy had a greater likelihood of excellent neurological outcome at 90 days without increasing the risk of symptomatic intracranial hemorrhage or mortality.
However, because none of the secondary efficacy analyses supported the primary finding, further trials are needed to confirm the results.
Large-scale stem cell bank enables global studies on genetic risk for Alzheimer’s
Besides environmental factors, genes have a strong influence on whether or not a person develops Alzheimer’s during their lifetime.
Through genome sequencing of DNA from large groups of healthy people and people with Alzheimer’s, some naturally occurring small changes in the DNA, known as genetic variants, were found to be more frequent in Alzheimer’s patients than in healthy people.
As more and more of these associated genetic “risk” variants are discovered, it is now possible to calculate a person’s individual polygenic risk score (PRS), meaning the likelihood of the person to develop Alzheimer’s, with high accuracy.
Despite this progress, it is still largely unknown how genetic risk variants, or combinations thereof, cause Alzheimer’s in individual patients and more specifically, how risk variants impact the health and function of brain cells.
To address this, researchers in the UK Dementia Research Institute at Cardiff University, UK, have now generated the first large-scale stem cell bank from over 100 individuals selected for extremes of Alzheimer’s PRS, which had previously been determined by genome sequencing.
The results of the work show that about two thirds of the donors had been diagnosed with Alzheimer’s and had a relatively high PRS while one third were cognitively healthy, age-matched individuals with a low PRS.
Blood cells from these individuals were genetically engineered to turn them into induced pluripotent stem cells (iPSCs), which are immature cells capable of generating all cell types of the body.
The new “iPSC Platform to Model Alzheimer’s disease Risk” (IPMAR) resource will be made available to researchers worldwide to facilitate studies on the impact of risk variants in iPSC-based cellular models of AD in the lab.
Stressful life events linked to an increased risk of Alzheimer’s disease
Stressful life events and grief over the loss of a partner in particular has been linked to alterations in biological processes associated with Alzheimer’s disease, while unemployment and financial loss have been associated with structural differences in the brain.
In Alzheimer’s disease, changes in the brain, such as alterations in the levels of certain proteins, can occur years before the first symptoms appear. For example, a lower ratio of amyloid beta 42/40 is observed; this ratio compares the concentrations of two forms of the protein.
Since amyloid beta 42 is more likely to aggregate in the brain, a decrease in this ratio in the cerebrospinal fluid usually reflects greater amyloid beta deposition in brain tissue, making it an important early indicator of Alzheimer’s disease.
Higher levels of phosphorylated tau, which causes neuronal damage, and neurogranin, which increases when connections between neurons are lost, are also found.
The death of a partner was associated with changes in these biomarkers: a lower amyloid beta 42/40 ratio (an effect that was more pronounced in men), and higher levels of phosphorylated tau and neurogranin (effects that were more pronounced in women).
All of these effects were more pronounced in people with lower levels of education.
Conversely, unemployment and economic losses were associated with a lower grey matter volume in key brain regions responsible for emotional and cognitive regulation.
Gender differences were also evident in these effects; unemployment affected men’s brains more, while economic losses had a greater structural impact on women’s brains.
A previous study by the same group already showed that exposure to stressful life events in middle age can increase vulnerability to Alzheimer’s disease.
However, the prevalence and impact of stressful life events varies according to certain social determinants, such as gender and education; women and people with lower levels of education experience more stressful life events, and it is also in these groups that the prevalence of Alzheimer’s is most prevalent.
The research showed that different stressful situations affect men and women differently.
“Men seem to be more negatively affected by the loss of a partner (which affects amyloid-related proteins) and unemployment (which reduces grey matter),” said Eider Arenaza-Urquijo, ISGlobal researcher and senior author of the study.
“This may be because men tend to have fewer close relationships, making the loss of a partner more isolating, so the loss of a partner is more isolating for them, and because unemployment carries a greater social stigma for men.”
