Could the Historical Transition from Segmented to Monophasic Sleep Explain the Modern Insurgence of Alzheimer’s Disease and Related Dementias?

In their article recently published in the Journal of Alzheimer’s Disease, Finch and Burstein [1] examined the theory according to which Alzheimer’s disease and related dementias (ADRD) might be a phenomenon of modern times. For this purpose, they systematically assessed and carefully appraised a vast corpus of standard editions of Greek and Latin texts, including ancient medical and philosophical texts discussing the human life cycle, in particular in the elderly, from the 8th century BCE to the 3rd century CE. Ancient Greek and Roman texts have been found to scarcely mention severe cognitive decline, memory loss, and dementia, focusing more on the physical aging aspects (“the old as bent with age, weak, and vulnerable”, portrayed in the early 7th Century BCE Homeric Odyssey) [1]. The ailments of the elderly include “urinary, digestive, and physical disorders; dizziness and insomnia; and deafness and blindness”, but not memory loss [1]. Aristotle and his colleague Theophrastus describe cognitive aging, which, however, does not appear to be characterized by what we would label as dementia [1].

Derived from the Latin root “de-mens”, meaning “being out of one’s mind”, this word has been increasingly used since the 13th century, mentioned within the medical community since the 18th century, and considered as a distinct nosological entity since Alzheimer’s seminal case published in 1906 [2]. Differently from the contemporary viewpoint, in ancient times, dementia was not associated with aging, and, on the contrary, intellectual sharpness past the age of sixty years was the norm in these societies, with only minor memory lapses being recognized.

Finch and Burstein [1] were able to identify only four instances of significant cognitive decline potentially akin to ADRD, mostly linked to environmental factors, such as air pollution and lead exposure (drinking water from leaded pipes, sapa-sweetened wine, and using poisonous leaded cosmetics). Solon in 6th BCE Athens gave the earliest mention of age-related memory loss, while instances of dementia were reported and described by Pliny the Elder, the satirist Juvenal, the Greek physician Galen, personal physician to the Roman emperor Marcus Aurelius, and Censorinus, author of an encyclopedia of general knowledge.

Besides environmental exposures, other factors can also account for the likelihood of ADRD being less common in ancient times, such as higher levels of physical activity, different (healthier) dietary habits, and, more broadly, lifestyles, including the way of sleeping (both from a quantitative and qualitative standpoint). To strengthen their assessment and get more insights, Finch and Burstein [1] make a parallelism with an indigenous community dwelling in Bolivia, the Tsimane people, who have attracted scholarly interest for their low incidence of cardiovascular disease, dementia, and high levels of physical activity. High rates of infectious diseases and high loads of parasites have also been reported in this population, with only mild cognitive issues and rare dementia cases among Tsimane elders. High-resolution CT brain imaging revealed that the cerebral cortex’s age-related atrophy occurs 30% more slowly compared to two reference samples from modern economies. Individuals with dementia exhibited a higher frequency of APOE E4/E4 genotype, with the E4 allele present at the upper normative range of 32%. The overall occurrence of dementia among the Tsimane population aged 60 and above is 1.2% (crude prevalence), which is less than a fifth of the prevalence rates in the US (8%) and Europe (6.2%) [1, 3].

The methodology adopted by Finch and Burstein [1] and the parallelism with an indigenous population are interesting for two major reasons. First, humanities and science are usually siloed apart while the work by Finch and Burstein [1], showing that the high prevalence of advanced dementia seen today was not documented in ancient Greco-Roman times, is a valuable example of how historical investigations can provide insights into why ADRD prevalence is much higher in modern times. Moreover, this approach reminds us of the historical work carried out by Roger Ekirch [4–6], who appraised ancient textual corpora and found that sleep has a biology, but also a (social) history. Monophasic sleep, which is the pattern where all of the day’s sleep is consolidated into one long period, is the most common sleep pattern in modern societies, typically involving around 7–9 hours of continuous sleep at night. Being characterized by a single, uninterrupted sleep period, often aligned with the natural day-night cycle, this pattern is often seen as more convenient in modern society due to its alignment with standard work and life schedules [6, 7]. On the contrary, segmented sleep usually involves two major periods of sleep over a 24-hour cycle, rather than a single block, including the well-known siesta culture, which incorporates the practice of a daily short nap. Historically, of note segmented sleep patterns were more common in pre-industrial societies and are still observed in some cultures (including indigenous communities) [8–12] and certain age groups (like infants and the elderly) [13].

In a previous study [9] conducted within the umbrella of the “Tsimane Health and Life History Project” (THLHP), data were actigraphically collected about sleep variability in the Tsimane population, from 120 Tsimane adults (67 females), aged between 18–91 years, over an average of 4.9 nights per participant. The authors demonstrated unique sleep ecology in this non-electrified, small-scale subsistence population of forager-horticulturalists, finding that only 31% of the total variability in sleep duration could be attributed to differences between individuals, with the remaining 69% due to variations within individuals from night to night, without any significant differences in sleep duration among different days of the week for the Tsimane. The variability in sleep duration was primarily due to fluctuations in the time of falling asleep, particularly among men, with activities such as hunting, fishing, household chores, and watching television being linked to later bedtimes, later sleep onset, and reduced total sleep duration. These minimal variations in sleep duration based on the day of the week significantly differed from patterns observed in industrialized nations, like the USA, where weekend “sleeping-in” primarily drives nightly sleep variability. Tsimane sleep patterns remained synchronized with natural light cycles, suggesting an adaptive strategy to environmental and social demands without the influence of electric lighting or structured work schedules.

The transition from segmented to monophasic sleep brought about by industrialization and the advent of artificial lighting has impacted sleep health, being paralleled by sleep deprivation, and increased sleep disturbances, such as insomnia. This shift in sleep patterns is coupled with dramatic changes affecting various lifestyle factors, including dietary changes and increased consumption of processed foods, caffeinated beverages, and energy drinks, as well as decreased physical activity levels. These factors can compound the effects of altered sleep patterns on health, resulting in further neuroinflammation, generation of reactive oxidative species, and glymphatic system failure [14–16], thus favoring the development of neurodegenerative conditions, including dementia [17, 18].

In conclusion, the research conducted by Finch and Burstein [1] offers a compelling examination into the historical prevalence of ADRD, suggesting that these conditions may not have been as common in ancient times as they are today. Their systematic analysis of ancient Greek and Roman texts, alongside the comparison with the Tsimane community, a pre-industrial population residing in Bolivia, provides valuable insights into how lifestyle factors, including physical activity, diet, health status, and underlying comorbidities (high rates of infections versus low rates of cardiovascular disease), might influence the incidence of cognitive decline and dementia. This interdisciplinary approach, bridging humanities and scientific research, not only challenges the notion that ADRD is an inevitable (“normative”) consequence of aging but also highlights the potential impact of modern lifestyle choices on cognitive health.

By drawing parallels with historical sleep patterns and those of the Tsimane people, we added a layer of complexity to Finch and Burstein’s work [1], underscoring the importance of considering a wide range of factors, from environmental to cultural, in understanding and potentially mitigating the prevalence of ADRD in contemporary society.

Taken together, these observations remind us of the intricate interplay between our biological makeup and the environment we inhabit, suggesting that lessons from the past, coupled with observations from diverse contemporary populations, could dissect the complexities of ADRD pathogenesis, unravel their multifaceted and interconnected nature, and enable the understanding of the intricate web of interactions. This could inform more effective public health strategies to combat the rising tide of dementia and cognitive decline in modern times by targeting modifiable risk factors in a tailored fashion [19].