Research Highlights From Padmaja Genesh (June 2020)
Study Results Offer New Hope for Treatment of Patients with Dementia
In a paper published online in the , TauRx reported that the drug it is developing for treatment of Alzheimer’s disease (hydromethylthionine) also has significant pharmacological activity in behavioural variant fronto-temporal dementia (bvFTD).
The study reports the relationship between treatment dose, blood levels and pharmacological activity of the drug hydromethylthionine on the brain in 176 patients with bvFTD.
The results showed that, even at the lowest dose of hydromethylthionine tested (8 mg/day), the drug (taken as a tablet) produced statistically significant concentration-dependent effects on clinical decline and brain atrophy with results similar to those reported recently in Alzheimer’s disease (AD).
Hydromethylthionine blocks abnormal aggregation in the brain of the proteins linked to over 80% of bvFTD (tau protein and TDP-43 protein).
The analyses suggest that a dose of about 30 mg/day would be optimal for treating bvFTD and could reduce the rate of disease progression even more. TauRx now plans to test this dose in a placebo-controlled confirmatory trial.
Association of Hypercholesterolemia with Alzheimer’s Disease Pathology and Cerebral Amyloid Angiopathy
The association of high cholesterol (HC) levels in blood with Alzheimer’s Disease (AD) in human studies has not been consistently established.
The researchers aimed to investigate the relationship between HC and risk of AD neuropathology in a large national sample with autopsies.
This study used neuropathological and clinical data from 3,508 subjects from the National Alzheimer’s Coordinating Center (NACC) who underwent autopsies from 2005 to 2017. Demographic and clinical characteristics, as well as neuropathological outcomes were compared between subjects with and without HC. Associations between HC and AD neuropathology were examined by multivariate ordinal logistic regressions adjusting for potential confounders.
HC was not associated with any AD neuropathology in a model only adjusting for demographic variables. However, HC was significantly associated with higher neuritic and diffuse plaque burden, more neurodegeneration, and more severe cerebral amyloid angiopathy when analyzed in a multivariate model controlling for comorbidities.
Conclusion: This study suggested that HC was associated with increased severity of AD brain changes, which could only be partially accounted for by ApoE genotype. The associations were not mediated by cerebrovascular conditions.
Journal: Journal of Alzheimer's Disease, vol. 73, no. 4, pp. 1305-1311, 2020
Living in Racially Segregated Neighborhoods May Not Be Good for Cognitive Health
Black individuals who lived in racially segregated neighborhoods throughout young adulthood performed worse on certain cognitive tests as early as midlife. Black Americans who live in segregated neighborhoods throughout young adulthood may have signs of possible cognitive decline by the time they reach midlife, according to a new study that tracked where participants lived over a span of 25 years.
While the study indicates an association, not a causal effect, between living in racially segregated neighborhoods and worse performance on cognitive testing in middle age, its findings point to yet another possible reason why there is a well-documented disparity in the risk of dementia for older black Americans compared with their white counterparts.
“The way we think conceptually about this is that residential segregation is really a factor upstream for a lot of other factors. When neighborhoods are segregated by race, that causes downstream effects such as low income and environmental exposures,” said lead author Michelle Caunca, PhD, who is a third-year medical student in the MD/PhD program at University of Miami Miller School of Medicine.
“The study gives us insight into how social and other contextual factors can play into cognitive pathology down the road,” Dr. Caunca said.
Loss of Functional Dentition is Associated with Cognitive Impairment
Although tooth loss is known to increase the risk of cognitive impairment and dementia, few studies have investigated the association between functional teeth including rehabilitated lost teeth and cognitive function.
The researchers investigated the associations of the numbers of functional teeth and functional occlusal units with cognitive impairment and cognitive function in late life.
The current study was conducted as a part of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), a community-based elderly cohort study. The researchers analyzed 411 participants who have agreed with the additional dental exam. Geriatric psychiatrists and neuropsychologists administered the Consortium to Establish a Registry for Alzheimer’s disease Assessment Packet Clinical and Neuropsychological Assessment Battery to all participants, and dentists examined their dental status.
Higher number of functional teeth and higher number of functional occlusal units, especially in the pre-molar region were associated with lower odds of cognitive impairment.
Conclusion: Loss of functional teeth and functional occlusal units (especially in the premolar region) were associated with increased cognitive impairment.
Mouth Bacteria Can Infect Brain Cells, Research Finds, Supporting Alzheimer’s Link
A type of mouth bacteria involved in gum disease is able to infect human brain cells, new research shows. The infection results in cellular changes that are similar to what is seen in , supporting a link between the bacteria and the neurodegenerative disease.
Their findings also support the idea that treatments targeting could have therapeutic benefit in Alzheimer’s.
Cortexyme is currently developing an investigational Alzheimer’s therapeutic candidate called COR388, which is an inhibitor of gingipains. COR388 was to be safe and well-tolerated in a Phase 1 clinical trial () conducted in healthy volunteers.
Its efficacy, safety, and tolerability in people with Alzheimer’s is now in the Phase 2/3 clinical trial (GingipAIN Inhibitor for Treatment of Alzheimer’s Disease; ). The GAIN trial is currently recruiting participants at multiple locations in the United States and Europe. Additional information can be found .
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