Dr Louis Bherer, Ph. D., Neuropsychologue

Professeur titulaire, Département de Médecine, Université de Montréal, Directeur adjoint scientifique à la direction de la prévention, chercheur et Directeur du Centre ÉPIC, Institut de cardiologie de Montréal.

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7 January 2026
Preventing Alzheimer’s disease by walking?

Overview

  • As we age, the brain gradually accumulates protein aggregates (amyloid plaques and tau fibrillary tangles) that can lead to neuronal death and a decline in cognitive function.
  • A study of 72-year-olds reports that regular physical activity slows the development of tau tangles and slows the progression of cognitive decline over the following ten years.
  • These benefits are observed at relatively modest levels of physical activity, around 5,000-7,000 steps per day.

During aging, brain neurons undergo several changes that significantly increase the risk of cognitive decline and, in the most severe cases, can lead to the development of neurodegenerative diseases such as Alzheimer’s. Two main abnormalities affecting nerve cells appear closely linked to brain dysfunction and are considered markers of the development of these pathologies: 1) amyloid plaques, which are insoluble aggregates located outside neurons, and 2) neurofibrillary tangles containing a modified (hyperphosphorylated) form of the tau protein, which aggregate inside neurons (Figure 1). These structures are highly toxic and, over time, cause disruption of nerve signals, neuronal cell death, and a significant reduction in brain tissue mass. Compared to a healthy brain, the brain of a person with Alzheimer’s disease occupies a smaller volume due to significant loss of brain tissue in the periphery (cortex) and in the hippocampus (the memory centre), accompanied by an enlargement of the ventricles to compensate for this loss of brain mass. Although the levels of both types of deposits (amyloid and tau) are generally correlated with the progression of neurodegeneration, it appears that the amount of abnormal tau protein is most closely linked to the severity of the symptoms of these diseases.

Figure 1. Schematic representation of a healthy brain and a brain affected by Alzheimer’s disease. Compared to the healthy brain (A), the brain affected by Alzheimer’s disease (B) shows atrophy of the cerebral cortex, a reduction in the volume of the hippocampus (the memory centre), and dilation of the ventricles as the disease progresses. This decrease in brain volume is a consequence of the destruction of neurons (neurodegeneration) caused by the accumulation of two main types of protein clumps: amyloid-beta (Aβ) plaques, located outside neurons, and neurofibrillary tangles of tau protein, located inside cells. These two abnormalities, typical of Alzheimer’s disease, can be detected using certain techniques, such as positron emission tomography (PET scan), and thus allow for the assessment of disease progression. Figure adapted from Neurotorium.org.

Cascade of events

As is the case for all chronic diseases (cardiovascular diseases, type 2 diabetes, chronic obstructive pulmonary disease (COPD), etc.), the clinical diagnosis of cognitive decline or Alzheimer’s-type neurodegeneration is the culmination of a long process, during which amyloid plaques and tau fibrillary tangles have gradually accumulated, without causing apparent symptoms, until reaching a certain stage where these abnormalities begin to affect normal brain function (Figure 2).

Figure 2. Proposed model of the evolution of different Alzheimer’s disease biomarkers during disease progression.In this model, changes in β-amyloid (red) precede the increase in abnormal tau protein aggregates (blue). The rise in both types of insoluble protein aggregates is thought to be responsible for cerebral atrophy, visible by magnetic resonance imaging (yellow), followed by a slight decline in cognitive function (purple) a few years later. This cognitive decline can subsequently evolve into more severe clinical impairment and progression to dementia (green). Adapted from Counts et al. (2016).

The onset of this sequence of events occurs much earlier than one might think: for example, a recent study revealed that amyloid plaque and tau protein levels began to be abnormally elevated as early as 18 and 11 years of age, respectively, before the clinical signs of dementia, followed by alterations in brain structure (8 years) and the onset of cognitive decline (6 years) before diagnosis (Figure 3). This long latency between the initial appearance of these different abnormalities and the development of cognitive problems at later ages is very interesting, as it suggests that it might be possible to prevent, or at least significantly delay, cognitive decline by halting the progression of the cascade of events that leads to neurodegeneration.

Figure 3. Evolution of different biomarkers in the 20 years preceding the diagnosis of Alzheimer’s disease. The trajectory of the markers is illustrated from the moment an abnormality begins to be detectable (-1.0) to its maximum (1.0), i.e., at the time of clinical diagnosis of the disease. It is proposed that this sequence of events reflects a cascade progression of Alzheimer’s disease, which begins several years before diagnosis with the accumulation of amyloid plaques (red, -18 years), followed by the formation of tau protein tangles (blue, -11 years), neuronal death (green, -8 years), and the gradual loss of cognitive functions (purple, -6 years). Adapted from Jia et al. (2024).

The importance of lifestyle habits

These methods do exist; as we recently mentioned, research in recent years suggests that approximately half of the cognitive impairments and dementias affecting the elderly population are linked to a number of lifestyle factors and could therefore be prevented.

Among these factors, a large number of studies suggest that regular physical activity is one of the most important lifestyle factors likely to delay, or even prevent, the onset of dementia, particularly when practiced from middle age (45 years and older). This reduced risk in more physically active individuals could be explained by several mechanisms, including the positive effect of exercise on cardiovascular and metabolic health, the formation of a cognitive reserve (which compensates for the loss of neurons affected by the damage characteristic of dementia), and a decrease in levels of abnormal tau proteins, responsible for the formation of fibrillar tangles toxic to neurons (see Figure 1).

Walking to slow neurodegeneration

Indeed, the results of a recent study suggest that this reduction in tau protein deposits could play a particularly important role in the protective effects of exercise on cognitive function. In this study, researchers recruited 296 cognitively healthy individuals (average age 72) and objectively measured their physical activity levels using a pedometer. Simultaneously, the levels of amyloid plaques and tau protein fibrillary tangles in the participants’ brains were measured at the beginning of the study using positron emission tomography (PET scans), and their cognitive abilities were assessed using standardized tests (see the legend for Figure 4). These various parameters were measured at regular intervals during a follow-up period of approximately 10 years, in order to evaluate the influence of physical activity levels on their evolution during normal aging.

The composition of the participant cohort closely reflects that of the general population, meaning it included a significant proportion (approximately one-third) of individuals with a high initial amyloid plaque burden. This distinction is important because these individuals are at higher risk of developing cognitive decline and are therefore the most likely to benefit from interventions that can slow its progression.

 Researchers observed that activity level does not influence the accumulation of amyloid plaques during aging, regardless of their initial level (Fig. 4A), confirming some previous observations (see here, for example). However, in participants at high risk of cognitive problems due to a high amyloid load, exercise has a marked effect on the evolution of other markers of neurodegeneration and on the preservation of cognitive function (Fig. 4B-D). In these individuals, for example, there is a significant reduction in the accumulation of tau protein aggregates compared to less active individuals (Fig. 1B), a less pronounced decline in cognitive performance (Fig. 1C), and a reduction in the severity of cognitive decline (Fig. 1D). According to the statistical models carried out by the authors, there is a direct link between these phenomena, that is to say that it is the reduction of the accumulation of tau by regular physical activity that would be responsible for the improvement of cognitive functions and the slowing of the severity of cognitive decline.

Figure 4. Associations between physical activity level and changes in various markers of cognitive decline. Results are presented for participants with a high (red) or low (blue) amyloid plaque load in the cerebral cortex at baseline. For each group, high physical activity (approximately 8,000 steps or more per day) is represented by solid lines, while low activity (3,000 steps or less) is represented by dashed lines.
A. The mean amyloid plaque load in the cortex of all participants in the cohort increases linearly over time but is not affected by physical activity level. B. Conversely, higher physical activity slows the increase in tau tangles observed in participants with a high amyloid load, an effect correlated with better preservation of cognitive function (C) and a decrease in the severity of cognitive decline (D). Note that cognition was measured using the PACC5, which establishes a score combining several aspects of cognitive functions (memory, attentional control, verbal fluency, etc.). A higher PACC5 score indicates better cognitive performance. The CDR-SOB (Clinical Dementia Rating Sum of Boxes) score, on the other hand, is a combined assessment of six different aspects related to cognitive health (memory, orientation, judgment and problem-solving, household activities, personal relationships, and self-care). Note that a score increase of 1–2 points, as observed in at-risk and inactive individuals in this study, reflects progression toward the early stages of Alzheimer’s disease. Adapted from Yau et al. (2025).

It is also worth noting that the amount of exercise needed to enjoy these benefits on cognitive functions seems relatively modest, both in terms of reducing tau entanglements and slowing cognitive decline, since the results suggest a maximal effect at around 5000-7000 steps per day, a level accessible to the majority of older people (Figure 5).

Figure 5. Effects of different exercise levels on tau tangle accumulation and cognition. Note that moderate physical activity (approximately 5000 steps per day) is sufficient to mitigate tau accumulation and cognitive deficits affecting individuals with high amyloid load. From Yau et al. (2025).

Overall, these results suggest that individuals at risk of developing cognitive problems during normal aging can significantly mitigate this risk by adopting a moderately active lifestyle, such as walking 5,000 to 7,000 steps daily, roughly equivalent to two 20-25 minute walks. In these individuals, exercise appears to slow the accumulation of toxic tau protein aggregates in neurons, thereby slowing the neurodegenerative process and preserving cognitive function.

How can a person determine if they are at high risk of cognitive decline due to elevated amyloid load? As mentioned earlier, it is estimated that approximately one-third of the population exhibits this profile, whether due to a genetic predisposition (for example, the presence of a specific form of the ApoE gene that disrupts lipid transport in neurons) or certain cardiovascular risk factors (high cholesterol, hypertension, type 2 diabetes) that can promote the accumulation of amyloid plaques and subsequently lead to the buildup of tau tangles, neuronal death, and a gradual loss of cognitive function. A person with a family history of Alzheimer’s disease (or other forms of dementia) or cardiometabolic problems would therefore be potentially at higher risk of developing higher levels of amyloid plaques with age and could thus greatly benefit from an active lifestyle to slow the development of cognitive problems. That being said, nobody really knows their amyloid load and their level of risk of cognitive decline; therefore, the simplest thing is to assume that we are at risk and to remain as physically active as possible throughout aging to maximize the chances of remaining healthy, both mentally and physically.

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