Dementia in the News

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SPECIAL REPORT: DEMENTIA

Research Identifies Promising Treatment for Alzheimer Disease, Other Cognitive Disorders

Erin O’Brien

Intranasal (IN) administration of an oxytocin derivative to the brain may be an effective treatment for Alzheimer disease and other cognitive disorders, according to a new study.

Leveraging previous research suggesting that introducing cell-penetrating peptides (CPPs) and a penetration-accelerating sequence (PAS) via structural modifications can benefit the nose-to-brain delivery pathway, the investigators created the oxytocin derivative PAS-CPPs-oxytocin. Their aim was to see if IN administration of this oxytocin derivative would help improve cognitive function in mice similarly to the more invasive intracerebroventricular (ICV) administration method.¹

“We have previously shown that oxytocin reverses amyloid-β peptide (25-35) (Aβ25-35)-induced impairment of synaptic plasticity in rodents,” said corresponding author Jun-Ichiro Oka, PhD, in a press release. “We wanted to see if PAS-CPPs-oxytocin could be delivered more efficiently to the mouse brain for clinical application, and if it improved cognitive functional behavior in mice.”²

The investigators conducted Y-maze and Morris water maze (MWM) tests and found that ICV administration of oxytocin showed memory-improving effects on the Aβ25–35-induced amnesia in both tests, while IN administration of the oxytocin derivative showed memory-improving effects in the Y-maze test. The investigators also found evidence that, following its IN administration, the fluorescein isothiocyanate-labeled oxytocin derivative was distributed throughout the brain.¹

“My team is the first to show that the oxytocin derivative can improve the Aβ25-35-induced memory impairment in mice,” Oka said in a press release. “This suggests that oxytocin may help reduce the cognitive decline we see in Alzheimer disease.”²

Oka, professor emeritus from Tokyo University of Science, further clarified that these findings are clinically useful because “the oxytocin derivative enters the brain more efficiently. Furthermore, since IN delivery is a noninvasive procedure, this modified version of the hormone could potentially be a clinically viable treatment for Alzheimer disease.”²

References

1. Takahashi J, Ueta Y, Yamada D, et al. Intracerebroventricular administration of oxytocin and intranasal administration of the oxytocin derivative improve β-amyloid peptide (25–35)-induced memory impairment in mice. Neuropsychopharmacol Rep. 2022;00:1-10.

2. Novel derivative of “love hormone” oxytocin improves cognition impairment in Alzheimer’s. News release. Tokyo University of Science. October 24, 2022. Accessed November 4, 2022. https://www.tus.ac.jp/en/mediarelations/archive/20221021_1000.html

Nonaffective Psychosis May Represent Modifiable Risk Factor for Dementia

Leah Kuntz

Individuals with nonaffective psychotic disorders are 2.5 times more likely than those without a nonaffective psychotic disorder to eventually develop dementia, representing a new avenue of modifiable risk, new research data show.¹

In the first high-quality systematic review looking at a range of psychotic disorders and their association with dementia risk, investigators gathered data from close to 13 million participants from 11 studies in 9 countries. The population of interest included adults 18 years or older with a clinical diagnosis of nonaffective psychosis based on ICD criteria. Results indicated that psychotic disorders may have a stronger link with dementia than other mental health disorders such as depression or anxiety. Studies of patients with typical and late-onset psychotic disorders, those with a higher percentage of women, and those with a younger minimum age at baseline showed the strongest associations. As such, the study authors wrote, “Our narrative synthesis provided some evidence that people with psychotic disorders tended to be younger at dementia diagnosis and that the association between psychotic disorders and dementia was stronger when the interval between the 2 diagnoses was shorter.”¹

Despite speculating that antipsychotics may have a role in the development of dementia, the investigators only found 2 studies exploring this link. Moreover, those studies showed mixed results. One found a protective effect; the other found an increased risk associated with second-generation antipsychotics but a protective effect for first-generation antipsychotics.

“Cognitive impairment and hallucinations can be symptoms of both dementia and psychotic disorders, so it is possible there could be a link between the 2 illnesses. This impairment could also limit people’s cognitive reserve, and increase their vulnerability to dementia symptoms,” said lead author Sara El Miniawi, MSc, of University College London in England.²

Regardless of the age at which an individual first develops a mental illness, those with psychotic disorders are at a higher risk of dementia later in life. Additionally, individuals with a psychotic disorder tend to be younger than average at dementia diagnosis, as young as their 60s.

Previous research indicated that 40% of dementia cases could be prevented or delayed by targeting risk factors across the life span. This study’s findings added to the list of modifiable risk factors for dementia.

“People with psychotic disorders are more likely to have other health conditions such as cardiovascular disease or obesity, which can increase the risk of dementia, while they are also more likely to have a poor diet, smoke, or use drugs, which may harm their health in ways that could increase their likelihood of developing dementia,” said Vasiliki Orgeta, PhD, an associate professor at the Division of Psychiatry, Faculty of Brain Sciences, at University College London.²

The investigators were not able to determine if effective treatment for psychotic disorders could mitigate the dementia risk, or if antipsychotic medication could be a factor, as there was limited and conflicting evidence.

References

1. El Miniawi S, Orgeta V, Stafford J. Non-affective psychotic disorders and risk of dementia: a systematic review and meta-analysis. Psychol Med. 2022;1-13.

2. Schizophrenia may increase dementia risk by 2.5 times. UCL News. October 6, 2022. Accessed November 2, 2022. https://www.ucl.ac.uk/news/2022/oct/schizophrenia-may-increase-dementia-risk-25-times