Medical Bulletin 19/ June/ 2024

A new analysis published in The Lancet journal's eClinicalMedicine suggested that timing blood pressure medication to align with a person's "chronotype"—whether they are a night owl or an early bird—may reduce the risk of heart attack.

Blood pressure drugs have been central to chronotherapy due to blood pressure's circadian rhythm, which peaks in the morning and dips at night. This healthy dip often vanishes in individuals with diabetes, kidney disease, and sleep apnea.

Some physicians have recommended taking medications at bedtime to restore the dip, but studies have produced mixed results, making this advice less common recently. However, emerging research suggests that timing medications to align with the body's natural rhythms could reduce side effects and enhance the effectiveness of various treatments, including vaccines, cancer therapies, and medications for depression, glaucoma, pain, and seizures.

In the study, the University of Dundee conducted the TIME study, a larger randomized, controlled trial in 2022. Researchers tracked over 21,000 participants taking hypertension drugs either in the morning or at night over several years and found no significant difference in cardiovascular outcomes.

To further investigate, researchers analysed the data based on participants' chronotypes, distinguishing between "night owls" (late-to-bed, late-to-rise) and "morning larks" (early-to-bed, early-to-rise). This additional analysis aimed to determine if aligning medication timing with personal sleep patterns could impact treatment efficacy.

The results showed that among the 5,358 participants in the TIME study, "night owls" who took their blood pressure medication at bedtime had a 34% lower risk of hospitalization for a heart attack. Conversely, their risk increased by 62% when taking the medication in the morning. For "morning larks," the pattern was reversed: taking the medication in the morning was associated with an 11% lower risk of heart attack, while taking it at night led to an 11% higher risk.

These findings highlighted the importance of considering individual chronotypes when prescribing blood pressure medication.

Reference: Filippo Pigazzani, Kenneth A. Dyar, Steve V. Morant, Céline Vetter, Amy Rogers, Robert W.V. Flynn, et al.; Effect of timed dosing of usual antihypertensives according to patient chronotype on cardiovascular outcomes: the Chronotype sub-study cohort of the Treatment in Morning versus Evening (TIME) study; EClinicalMedicine; DOI:https://doi.org/10.1016/j.eclinm.2024.102633

When stressed out, many of us turn to junk food for solace.

But a new University of Colorado Boulder research has found that a high-fat diet disrupts resident gut bacteria, alters behaviour and, through a complex pathway connecting the gut to the brain, influences brain chemicals in ways that fuel anxiety.

Stress eating, often characterized by consuming high-fat and sugary foods, can exacerbate anxiety. These comfort foods trigger short-term pleasure but can disrupt the body's natural balance, leading to fluctuations in blood sugar levels and hormone imbalances. Over time, this can negatively impact brain chemistry, increasing the likelihood of anxiety.

“Everyone knows that these are not healthy foods, but we tend to think about them strictly in terms of a little weight gain. If you understand that they also impact your brain in a way that can promote anxiety, that makes the stakes even higher,” said lead author Christopher Lowry.

In the study, researchers divided adolescent rats into two groups. One group received a standard diet containing approximately 11% fat for nine weeks, while the other group was fed a high-fat diet comprising 45% fat, primarily from saturated animal fats.

Throughout the study, researchers collected faecal samples to assess the animals' gut microbiome. After nine weeks, the rats underwent behavioural tests to evaluate the impact of their diets on anxiety and stress levels.

The results showed that compared to the control group, the rats on the high-fat diet unsurprisingly gained weight. However, they also exhibited significantly less diversity in their gut bacteria, a factor associated with poorer health.

Additionally, the high-fat diet group showed increased expression of three genes involved in the production and signalling of the neurotransmitter serotonin, particularly in a brainstem region linked to stress and anxiety. This reduced bacterial diversity and altered gene expression in the high-fat diet group underscore the potential impact of diet on mental health.

While serotonin is often billed as a “feel-good brain chemical, certain subsets of serotonin neurons can, when activated, prompt anxiety-like responses in animals. Notably, heightened expression of tryptophan hydroxylase has been associated with mood disorders and suicide risk in humans. To think that just a high-fat diet could alter expression of these genes in the brain is extraordinary. The high-fat group essentially had the molecular signature of a high anxiety state in their brain,” said Lowry.

Reference: de Noronha, S.I.S.R., de Moraes, L.A.G., Hassell, J.E. et al. High-fat diet, microbiome-gut-brain axis signaling, and anxiety-like behavior in male rats. Biol Res 57, 23 (2024). https://doi.org/10.1186/s40659-024-00505-1

A new study by researchers from Mass General Brigham, published in JAMA Neurology, suggested that whether a person inherits risk of Alzheimer’s disease from their mother or father influences risk of biological changes in the brain that lead to disease.

Alzheimer's disease is a progressive neurodegenerative disorder that primarily affects memory and cognitive function. It is characterised by the buildup of amyloid plaques and tau tangles in the brain.

Research has indicated that individuals with a maternal history of Alzheimer’s disease have an increased risk of developing the condition. This heightened risk is believed to be linked to genetic factors and mitochondrial DNA inherited from the mother. Mitochondria, which are crucial for cellular energy production, are exclusively inherited from the mother, and any mitochondrial dysfunction can contribute to the development and progression of Alzheimer’s disease.

In the study, researchers examined the family history of older adults participating in the Anti-Amyloid Treatment in Asymptomatic Alzheimer’s (A4) study, a randomized clinical trial aimed at preventing Alzheimer’s disease. Participants were asked about the onset of memory loss symptoms in their parents, whether their parents were ever formally diagnosed, or if there was autopsy confirmation of Alzheimer’s disease. Researchers then compared these responses and measured amyloid levels in the participants.

They found maternal history of memory impairment at all ages and paternal history of early-onset memory impairment was associated with higher amyloid levels in the asymptomatic study participants.

Researchers further observed that having only a paternal history of late-onset memory impairment was not associated with higher amyloid levels.

“If your father had early onset symptoms, that is associated with elevated levels in the offspring. However, it doesn’t matter when your mother started developing symptoms — if she did at all, it’s associated with elevated amyloid. It’s really interesting from a genetic perspective to see one sex contributing something the other sex isn’t. This work indicates that maternal inheritance of Alzheimer’s disease may be an important factor in identifying asymptomatic individuals for ongoing and future prevention trials,” said the authors.

Reference: Seto M, Hohman TJ, Mormino EC, et al. Parental History of Memory Impairment and β-Amyloid in Cognitively Unimpaired Older Adults. JAMA Neurol. Published online June 17, 2024. doi:10.1001/jamaneurol.2024.1763