The Dementia Continuum: Its Stages and How to Delay It

Have you ever had the experience of walking into the kitchen and forgetting why you did?  Or maybe you’ve forgotten an appointment because it slipped your mind.  These lapses in memory are normal, but sometimes become more concerning to us as we age.  Staying mentally sharp with age is often a focus for older adults.  It makes sense, especially when research shows that normal aging impacts memory and processing speed as early as our 20’s and progresses predictably throughout life.1 

These normal cognitive changes don’t always result in dementia or other brain diseases. However, at times they can indeed be early signals for neurodegenerative diseases, like Alzheimer’s disease (AD). AD is most prevalent in people 65 and older, not surprisingly around the same time that most start to wonder how to prevent it. But did you know that AD begins silently, with changes slowly building in the brain many years before symptoms even begin? Indeed, current evidence indicates that neurodegeneration develops along a “continuum” of time, with changes happening in the brain as much as 15-20 years before diagnosable symptoms arise.2,3 

While this might sound unsettling, it’s actually very good news. This means you have an opportunity right now to mitigate the risks associated with AD and other neurodegenerative diseases.  Actions taken early and consistently can be powerful ways to delay or prevent symptoms long-term. Read on to learn about the components that keep your brain balanced and the actions you can take now to promote a healthy mind later in life.

The Dementia “Continuum”

Your body, including your brain, is in a constant balancing act to maintain health for as long as possible. Many inputs that occur over the course of a lifetime, including genetics, diet, lifestyle, and social connections can impact it.2–5  These factors can step on either the gas or the brake on the path to disease, working together to keep the brain functioning and keep all the moving parts in check. Incredibly, your brain uses a myriad of compensatory mechanisms to maintain a working balance despite the stresses thrown at it throughout our lives.  However, if we neglect to care for our brain, it reaches a breaking point where those accumulated stresses can result in neurodegeneration, as in the case of AD.6  Taking protective actions before this breaking point is an important component of lifelong brain health.  The earlier you start, the greater impact your actions will have over time.

AD is a complex disease that impacts a complex organ, your brain.  You can see a graphic representation of the AD “continuum” in the diagram below, which is adapted from excellent scientific articles by Sperling et al. and Aisen et al.; in the diagram, you’ll see that AD progresses through three general stages2,3,6:

  1. Preclinical: no clinical symptoms exist, but progressive markers of disease accumulate, like amyloid-β (we’ll describe this later on)
  2. Mild Cognitive Impairment (MCI): some memory and cognitive loss without the loss of independence
  3. Dementia: progressive loss of function and independence (e.g., forgetting medication, difficulty with everyday tasks like dressing and bathing)

Within each stage a stepwise series of changes occur in the brain, represented by the curves in the figure. Each change is a step closer to a loss of balance in the brain and ultimately AD dementia.2,7  Let’s take a deeper look at each of these changes and how they impact your brain.

 Alzheimer's dementia continuum - NeuroReserve

Diagram adapted from Sperling et al. and Aisen et al. 


Amyloid-β accumulation:

Amyloid-β (amyloid-beta, or Aβ) is a protein that, under normal conditions, is important in the proper function of the brain.6,8  One of the first changes seen in AD is improper size and shape of the Aβ protein, causing it to aggregate (or clump) into plaques in brain tissue.  Aβ plaques are a hallmark of AD.2,6  In AD, the brain is unable to clear the altered Aβ,6 so it collects around brain cells (neurons), interfering with their function. It’s estimated that this accumulation begins at least 15 years prior to the start of cognitive symptoms.3,7

Synaptic dysfunction:

Synapses are information hubs in your brain, key to communication between cells of the nervous system.  They are the small spaces between two neurons that allow them to send and receive signals.  Aβ plaque accumulation impairs communication at synapses,9,10 which is where you see the second curve begin in the diagram.  As Aβ plaques accumulate, brain power takes a hit.  Signals can’t travel as quickly from one brain cell to the next.  Over time, these hits accumulate, resulting in progressive memory loss and cognitive dysfunction.6,9 This may take many years to result in symptoms, so it comes with the opportunity for prevention.9 

Tau-mediated neuronal injury (tangles):

Tau is another protein that is normally important in the structure and function of neurons.  It’s found inside neurons, with a role in stabilizing microtubules (the cell’s skeleton).  Aβ dysfunction triggers tau to become misshapen.  This misshapen tau begins to bind to itself instead of the cellular skeleton, forming tau fibers which get tangled within the neuron.9,10  These are called neurofibrillary tangles and, in combination with Aβ and synaptic dysfunction, are an important marker of AD progression (see the tau curve in the diagram).  Ultimately, neurofibrillary tangles proceed to accumulate until they prevent communication between neurons.6,9  Tau tangles appear to accumulate in specific regions of the brain involved with memory.9

Brain structure changes (atrophy):

Accumulating Aβ plaques and tau tangles can ultimately lead to the death of neurons.  As neurons in specific areas of the brain die, the volume of the brain is reduced.  The timing of this lays close to the onset of cognitive decline.  At this point, the brain can no longer maintain balance and becomes visibly smaller on an MRI scan.2,3


As the brain begins to lose volume and work less efficiently, the final stages along the continuum are not physical changes, but changes in the ability to think and function.2,3,7  In diagram, it’s clear that the rise of cognitive dysfunction signals the entrance to the state of mild cognitive impairment (MCI).2  The symptoms associated with this stage may be noticeable to both you and those close to you, but they are not significant enough to impact your ability to perform daily tasks.11  Symptoms may include becoming more forgetful, forgetting important appointments or events, feeling more overwhelmed by making plans or following instructions, and losing your train of thought in the middle of a conversation.3

Clinical Function:

Though not all with MCI will progress further, in AD it progresses to dementia that interferes with one’s ability to function independently.2,3 With continuous decline in memory and reasoning, important behavioral and social skills also begin to decline.  At this point along the continuum, symptoms may include inability to handle finances, forgetting to take medications, and struggles with everyday tasks like using a phone, bathing, or dressing.3

Take Action Now for a Healthy Mind Later

Understanding the continuum of neurodegeneration should empower and motivate us no matter what stage we may be in.  In your own life, you can implement several known dietary and lifestyle changes to help “push away” the continuum and extend your “brainspan.”

 Pushing-out and delaying the Alzheimer's dementia continuum - NeuroReserve


Several key factors have been studied regarding AD, including regular physical activity, sleep quality, and maintaining social connections.  Physical activity is a highly impactful way to help keep your brain working like a well-oiled machine.  In fact, a meta-analysis of 16 studies that included a total of more than 160,000 participants concluded that regular exercise may reduce the risk of AD by 45%.4  Improving sleep quality is another way to reduce your risk of AD.  Studies have shown that poor quality sleep can increase deposits of Aβ in the brain.12  Finally, loneliness has been associated with twice the risk of developing cognitive decline and AD, although the reason for this is still under investigation.5


The food you eat has a powerful impact on your brain.  It’s important to remember that although the brain is only 2-3% of our weight, it consumes a staggering 20-25% of our energy.  It is always “hungry.”  Eating for brain health now has the potential to significantly reduce your risk of developing AD.  More specifically, the Mediterranean and MIND diets have a large and growing body of evidence that connects these patterns of eating with lower risk of neurodegenerative disease like AD and Parkinson’s disease. In fact, just adding some of the foods recommended on the MIND diet can reduce your risk of AD by 35%, and strict adherence can reduce it by as much as 53%.13  Brain-healthy foods to eat regularly include leafy greens, fruits (especially berries), healthy fats (from olive oil, avocados, nuts, seeds), and fish.  For more information about these dietary patterns, see our previous article here.


We know much more today about how to intervene in the silent stages of neurodegenerative diseases than we did even a decade ago. Take advantage of the fact that investing in your brain health early will have the biggest returns. Act today to keep your brain healthy throughout life! 


Changing your diet is a lifelong learning process.  It’s normal to feel a little lost as you start a new way of eating, but there are fortunately some great resources to get started regarding your dietary choices and day-to-day cooking.  We have our own resource, Brain Table, which is a collection of delicious recipes designed for lifelong brain health, rich with brain-supportive ingredients.  You’ll also find additional resources and brain-healthy recipes at Brain Health Kitchen, which was started by Annie Fenn, M.D., one of our medical and dietetics advisors.     

And despite our best efforts, we can still experience gaps in proper brain nutrition.  Supplements can complement your dietary goals by filling in gaps as needed. Quality supplements targeting brain-supportive nutrients, like RELEVATE, can be useful to help your brain get everything it needs to stay healthy.

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  1. Park, D. C. et al. Models of visuospatial and verbal memory across the adult life span. Psychol. Aging 17, 299–320 (2002).
  2. Sperling, R. A. et al. Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimer’s Dement. 7, 280–292 (2011).
  3. Aisen, P. S. et al. On the path to 2025: Understanding the Alzheimer’s disease continuum. Alzheimer’s Research and Therapy vol. 9 (2017).
  4. Hamer, M. & Chida, Y. Physical activity and risk of neurodegenerative disease: A systematic review of prospective evidence. Psychological Medicine vol. 39 3–11 (2008).
  5. Wilson, R. S. et al. Loneliness and risk of Alzheimer disease. Arch. Gen. Psychiatry 64, 234–240 (2007).
  6. De Strooper, B. & Karran, E. The Cellular Phase of Alzheimer’s Disease. Cell vol. 164 603–615 (2016).
  7. Dubois, B. et al. Preclinical Alzheimer’s disease: Definition, natural history, and diagnostic criteria. Alzheimer’s Dement. 12, 292–323 (2016).
  8. Brothers, H. M., Gosztyla, M. L. & Robinson, S. R. The physiological roles of amyloid-β peptide hint at new ways to treat Alzheimer’s disease. Frontiers in Aging Neuroscience vol. 10 118 (2018).
  9. Bloom, G. S. Amyloid-β and Tau The Trigger and Bullet in Alzheimer Disease Pathogenesis. (2014) doi:10.1001/jamaneurol.2013.5847.
  10. Chen, Y., Fu, A. K. Y. & Ip, N. Y. Synaptic dysfunction in Alzheimer’s disease: Mechanisms and therapeutic strategies. Pharmacol. Ther. (2018) doi:10.1016/j.pharmthera.2018.11.006.
  11. Jongsiriyanyong, S. & Limpawattana, P. Mild Cognitive Impairment in Clinical Practice: A Review Article. doi:10.1177/1533317518791401.
  12. Ju, Y. E. S. et al. Sleep quality and preclinical Alzheimer disease. JAMA Neurol. 70, 587–593 (2013).
  13. Morris, M. C. et al. MIND diet associated with reduced incidence of Alzheimer’s disease. Alzheimer’s Dement. 11, 1007–1014 (2015).
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