BlogGeneralFactsheetsWhat is the impact of early life on brain and cognitive reserve?

What is the impact of early life on brain and cognitive reserve?

What is the impact of early life on brain and cognitive reserve?

Authors: Irina Benedek, Oana Vanta

Keywords: reserve capacity, brain reserve, cognitive reserve, early life, dementia

What is the impact of early life on brain and cognitive reserve?

A growing number of specialists realize that neurodegenerative disorders begin years before clinical signs appear. Generally, it is less recognized that the foundation for the risk of acquiring neurodegenerative pathologies may be set in the very early stages of life. As disorders like Alzheimer’s dementia are typically diagnosed in the later stages of life, it could also seem like a long shot since variables that generate the disease take place 70 to 80 years before its diagnosis [1]. 

On the other hand, the adult brain’s structural and functional organization is established mainly during pregnancy and early years after birth; therefore, it is feasible that inconsistencies in these processes increase the brain’s susceptibility to disease in later life [1]. 

The current factsheet focuses on the brain’s reserve capacity, which also claims that elements present in early life significantly impact the brain’s reserve capacity, which in turn affects how different neurological pathologies impact people later on [1].

What are the brain and cognitive reserve?

  • The concept of reserve capacity:

Many people experience cognitive deterioration as they age, and others acquire a type of dementia. Although neuropathological indicators of dementia diseases can frequently be identified in patients’ brains, there is typically no direct correlation between clinical symptoms and the level of neuropathology [1].

  • Postmortem examinations of cohort members in a certain study revealed that cognitively healthy centenarians apparently had a degree of neuropathology; nevertheless, they had varying amounts of amyloid-, neurofibrillary tangles, and neuritic plaques [1]. 
  • The idea of reserve capacity – originally described as the brain’s capability to successfully buffer changes brought on by natural aging and deal with pathological damage – can be used to explain why there is no correlation between neuropathology in the brain and clinical symptoms of cognitive decline [2]. 
  • Brain reserve (BR) and cognitive reserve (CR) are two distinctive forms of reserve capacity that are often identified as follows:
    • BR is frequently understood as the brain’s physical or structural components, such as its size, the number of neurons, and the connections it comprises [3].
    • CR is the ability to adapt cognitively to aging-related conditions. It has been described as the adaptability of cognitive processes that aid in determining differential susceptibility of day-to-day function to brain aging, pathology, or insult [3] (Figure 1).

      WhatsApp Image 2023 11 28 at 10.35.47

      Figure 1. Brain reserve vs. Cognitive reserve
  • Markers of Brain Reserve, Cognitive Decline, and Dementia

There is a significant importance of reserve as a potential defense against the emergence of neurodegenerative diseases: 

  • Since it represents the maximum attained brain size, the intracranial volume (ICV) appears to be a reliable indicator of brain reserve [1].
  • A smaller ICV has been linked to a greater incidence of dementia, moderate cognitive impairment, and an earlier age at which Alzheimer’s disease manifests [4]. 
  • When neuropathology was considered, recent studies revealed that intracranial volume was positively related to cognitive functioning. However, its measurement involves MRI scanning, which adds cost and time to the process [1]. 
  • Markers of Cognitive Reserve, Cognitive Decline, and Dementia

It has been proposed that certain factors may operate as proxy markers for CR (Figure 2).

WhatsApp Image 2023 11 28 at 10.35.46

Figure 2. Proxy markers for cognitive reserve

Each year of higher education lowered the incidence of dementia by 7%. [5]. Higher levels of physical exercise were also linked to a lower risk of dementia development [6]. Evidence for food variables preventing dementia was also revealed. Interestingly, the interaction of several CR components appears to be highly linked to dementia risk [1].

What role does the Developmental Origins of Health and Disease hypothesis play on the risk of developing dementia?

This concept suggests that variables playing in the first days of life, from conception to roughly the age of two, may program the fetus’s or child’s anatomy and physiology, impacting the probability that a disease will occur later in life.

  • The brain is susceptible to external effects such as stress or malnutrition at this crucial growth stage. 
  • The brain may be able to adjust to improper conditions; the adaptation process is often advantageous from the standpoint of evolution since it gives the organism a chance to adapt itself to the anticipated environment within a single generation. 
  • The brain needs environmental cues to effectively develop during these critical phases and increase neuroplasticity [1].

Due to these factors, the growing brain is highly susceptible to challenging early-life situations [1].

Concerning somatic diseases like cardiovascular disease, type 2 diabetes, and even mental health problems (e.g., depression), there is a wealth of evidence supporting the “Developmental Origins of Health and Disease concept” [1]. 

Negative factors might raise the risk for neurodegenerative diseases in later life. These factors include: 

  • maternal smoking 
  • drug use 
  • undernutrition 
  • overnutrition
  • stress
  • mental health issues
  • toxin exposure 
  • small size at delivery [1].WhatsApp Image 2023 11 28 at 10.35.47 1

Birthplace, a reflection of the early life environment, is associated with dementia, with a higher risk for those born under less favorable conditions. For instance, patients with dementia were more likely to be born in rural areas than in metropolitan regions, or in locations with a high rate of infant or stroke mortality [1]. 

Early-life socioeconomic deprivation has repeatedly been found to be linked to dementia risk and late-life cognitive impairment, particularly when additional risk factors such as a family history of dementia or APOE-E4 carrier status were present [1]. 

A further element that appears to increase the risk for dementia is having had adverse experiences as a youngster. Moreover, early parent loss raises the likelihood of developing dementia [1].

What are the conclusions?

  • A poor early start in life may result in a smaller brain and cognitive reserve capacity and a smaller potential to maintain reserve, limiting the ability to buffer the effects of age-related neuropathology and increasing the risk of developing dementia disorders in later life [1]. 
  • Various factors play a negative role in the first 1,000 days of life and lead to a poor early start.
  • Indicators of BR, CR, and BM have been linked to numerous prenatal factors, including maternal malnutrition, stress, and depression, drug and alcohol use, exposure to chemicals, air pollution, and heavy metals, as well as small size at birth.
  • Contrary to what was previously believed, there is evidence that adult brains may undergo neurogenesis (the growth of new neurons) and synaptogenesis (the development of synapses). This implies that BR might rise with age, but it is still debatable. It is believed that the same elements that affect BM are also at play here, including social contacts, exercise, and food.
  • Robust pre-clinical data support the role of physical exercise as a critical regulator of synaptogenesis and neurogenesis, which is supported by some evidence in humans [8]. This looks like another way that early life circumstances may affect BR, given the data that early environments can encode physical activity levels in later life [1].

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  1. de Rooij SR. Are Brain and Cognitive Reserve Shaped by Early Life Circumstances? Front Neurosci. 2022;16:825811. doi: 10.3389/fnins.2022.825811.
  2. Beker N, Ganz A, Hulsman M, Klausch T et al. Association of cognitive function trajectories in centenarians with postmortem neuropathology, physical health, and other risk factors for cognitive decline. JAMA Netw. Open 2021.  4:e2031654. 10.1001/jamanetworkopen.2020.
  3. Stern Y, Arenaza-Urquijo EM, Bartrés-Faz D, Belleville S et al. Whitepaper: defining and investigating cognitive reserve, brain reserve, and brain maintenance. Alzheimers Dement 2020. 16 1305–1311. 10.1016/j.jalz.2018.07.219
  4. Wolf H, Julin P, Gertz HJ, Winblad B, Wahlund LO. Intracranial volume in mild cognitive impairment, Alzheimer’s disease and vascular dementia: evidence for brain reserve? Int. J. Geriatr. Psychiatry 2004. 19 995–1007. 10.1002/gps.1205
  5. Xu W, Tan L, Wang HF, Tan MS, et al. Education and risk of dementia: dose-response meta-analysis of prospective cohort studies. Mol. Neurobiol. 2016. 53 3113–3123. DOI: 10.1007/s12035-015-9211-5
  6. Beydoun MA, Beydoun HA, Gamaldo AA, Teel A, et al. Epidemiologic studies of modifiable factors associated with cognition and dementia: systematic review and meta-analysis. BMC Public Health 2014. 14:643. DOI: 10.1186/1471-2458-14-643
  7. Gluckman PD, Hanson M. (2006). The Developmental Origins of Health and Disease. New York, NY: Springer.
  8. Ambrogini P, Lattanzi D, Ciuffoli S, Betti M. Physical exercise and environment exploration affect synaptogenesis in adult-generated neurons in the rat dentate gyrus: possible role of BDNF. Brain Res. 2013. 1534 1–12. 10.1016/j.brainres.2013.08.023

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