A growing body of research suggests that disruptions in the circadian rhythm are not simply a consequence of neurodegenerative diseases like Alzheimer’s,  they may play a meaningful role in their development and progression. Recent work from Washington University School of Medicine has shown that key brain support cells, including microglia and astrocytes, lose their normal 24-hour patterns of activity in Alzheimer’s-affected brains [3, 4, 9]. These glial cells typically follow tightly regulated circadian schedules that help clear metabolic waste, regulate inflammation, and maintain neuronal stability [1, 4, 10]. When their internal timing breaks down, the systems essential for brain maintenance begin to fail.

This reinforces a central principle in biology:

The brain does not just rely on biological processes working correctly, it relies on them happening at the right time.

The Science of Circadian Timing

Circadian rhythms are cellular timing mechanisms found in nearly every tissue in the body. They regulate:

• Sleep and wakefulness

• Hormonal signalling

• Immune function

• Metabolic activity

• Neural repair and waste clearance

This timing system ensures that brain maintenance intensifies during sleep, when metabolic demand is low and the glymphatic system can more effectively clear beta-amyloid and tau proteins [6, 7].

However, when circadian rhythms are disrupted, through irregular sleep, late-night light exposure, shift work, chronic stress, or social jet lag, the timing of these repair processes becomes desynchronized. Inflammation increases, cellular stress rises, and toxic proteins may accumulate more rapidly [11, 14].

In this framework:

Sleep disruption is not just a symptom of neurodegenerative disease, it may be part of the mechanism driving it.

Circadian Disruption as a Feedback Loop

Circadian disruption appears early in Alzheimer’s disease,  well before significant cognitive symptoms develop [9, 13]. Individuals frequently experience:

• Fragmented or non-restorative sleep

• Daytime fatigue

• “Sundowning” (late-day confusion or agitation)

When circadian clocks falter:

• Microglia tend toward pro-inflammatory activity [3, 10]

• Astrocytes lose stability in neural support functions [4]

• Waste clearance becomes less efficient [6, 7]

This forms a self-reinforcing cycle:

Circadian disruption accelerates neurodegeneration → neurodegeneration further disrupts circadian timing [10, 11].

Maintaining Circadian Stability in Daily Life

The encouraging insight is that circadian rhythms are highly trainable, and can be stabilised using consistent daily cues known as zeitgebers.

Key actions include:

1. Wake and sleep at consistent times, including weekends.

2. Obtain morning daylight exposure within the first hour of waking.

3. Dim lights in the evening, especially blue-enriched light from screens.

4. Maintain regular meal timing, avoiding late-night eating.

5. Move daily, ideally outdoors to combine light and locomotion.

These are not simply “sleep hygiene tips.”

They are biological synchronisation signals that reinforce cellular timing across the brain and body [1, 2, 12].

The Operating System of Brain Health

Circadian rhythm functions as an organising system for cellular repair, metabolic efficiency, immune balance, and cognitive maintenance. When this system loses its structure, deterioration accumulates over time.

Preserving circadian integrity is therefore not only about improving sleep quality,  it is a central strategy for sustaining long-term brain health and resilience.

 References

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