As the number of elderly people increases worldwide, the effects of impairments related to age, such as dementia, become more relevant. Dementia results in cognitive dysfunction, which can impair judgement, impair decision making, affect communication, and impede or prevent independent life.¹ Although dementia can be diagnosed in many different stages, the main hallmark is cognitive decline seen with memory and higher executive function.¹ The cause of this decline can be a result of multiple factors dependent on site and progression of lesions and neuron loss.¹ Dementia may present in many different forms, each portraying their own unique symptoms. The different forms include Alzheimer’s disease (AD), frontotemporal dementia, progressive aphasias, Lewy-body dementia, and posterior cortical atrophy, among others.¹ This article will focus on AD with the primary symptom being impairment of recent memory. Figure 1 depicts the brain regions that are typically involved with mild to severe stages of AD.

As individuals age their brain shrinks in size but does not lose a significant number of neurons. In the case of Alzheimer’s disease, neurons stop functioning, lose connections, and start to die. This loss of brain mass when compared to a healthy brain is depicted in Figure 2. The beginning stages of AD is associated with the loss of neurons involved in memory in the entorhinal cortex and hippocampus. As the disease progresses, language, reasoning, and social behavior is affected. Many patients lose the ability to live independently, and the final stage of Alzheimer’s typically results in fatality. AD is characterized by the presence of amyloid plaques and intraneuronal neurofibrillary tangles, both of which are insoluble and densely packed filaments. These filaments do contain soluble structures of amyloid-β peptides and tau for tangles.⁶ Amyloid-β peptides are proteolytic fragments of transmembrane precursor enzymes and tau is a brain-specific, axon, and microtubule protein. Alterations in this peptide and protein are used for detection of Alzheimer’s disease. Chemical changes associated with AD cause tau to detach from microtubes and form tangles inside the neurons, blocking synaptic communication. The spreading of tau tangles and amyloid plaques cause cognitive decline, the hallmark of AD. Another cause of Alzheimer’s disease is through chronic inflammation caused by the buildup of glial cells, non-neuronal cells, in the central nervous system and peripheral nervous system.⁶ These amyloid plaques produced by amyloid-β peptides are normally destroyed by microglia, but the failure of these cells causes increased buildup. Microglia continue to send the signals for inflammation, but fail to destroy the plaques, further damaging the neurons that they surround. These buildups could also cause problems with blood vessels that lead to β-amyloid deposits in brain arteries, atherosclerosis, and strokes.⁸ Reduced blood flow and oxygen to the brain can be caused by the blockage of arteries leading to the breakdown of the blood brain barrier, leading to further life-threatening problems. Without this flow of oxygen, brain regions begin to die causing brain atrophy.

Alzheimer’s disease not only affects memory, but it can also affect one’s mood, quality of life, daily activities, and one’s need for care.¹⁰ There are many drugs being tested for the treatment of this disease, although none of them have been able to reverse the disease. The four drugs that are currently on the market for the treatment of Alzheimer’s disease are Donepezil, Galantamine, Rivastigmine, and Memantine.¹⁰ The first three drugs are acetylcholinesterase inhibitors for the treatment of mild to severe Alzheimer’s disease while the fourth drug is an NMDA receptor antagonist for the treatment of moderate to severe Alzheimer’s disease.¹⁰ Acetylcholinesterase is an enzyme that breaks down acetylcholine as nerve junctions. The inhibition of this enzyme leads to a higher concentration of acetylcholine in the brain and better communication between the nerve cells. NMDA receptors are important for synaptic plasticity and survival of neurons, but excessive activity, as seen with AD, causes excitotoxicity and promotes cell death. The use of receptor antagonists helps to reduce the excessive activity leading to survival of the neurons, even if neural plasticity is diminished.¹³ Like every drug on the market there are side effects, but without the reversal of the disease some people have opted to manage the disease in other ways. Neuroplasticity has gained traction in the research community as a possible treatment for dementia without the use of traditional drugs.
Neuroplasticity is the ability of the brain to “rewire” itself by establishing new neural connections. This rewiring could be the consequence of injury, developmental or environmental changes, or changes caused by sensory input.⁸ In the case of injury, the brain can reroute tasks that were normally associated with one area to a completely unrelated area in the brain. Neuroplasticity is also seen with establishing new skills to improve one’s memory. As people begin to age, a decline is seen in their memory, attention, and learning skills.⁸ Although, the ability for the brain to remain plastic and reroute connections does not degrade with age. Neuron growth can be stimulated through specific exercises on sensory input, movement, and cognitive patterns.
Neuroplasticity is a promising as treatment for both the patient and their family members. A study published in 2010 by Kolanowski, et al. looked at delirium superimposed on dementia (DSD) and certain activities used to facilitate plasticity.¹⁶ For individuals with dementia, delirium occurs in over half of the hospitalized adults, compounding their physical and cognitive burdens that were already present. The article defined delirium as a “state of confusion characterized by an acute onset, alteration of consciousness, change in cognition, fluctuating course, and reduced attention.”¹⁶ As individuals age their cognition declines which is correlated with diminished neurogenesis, the growth of nervous tissue, and plasticity in the hippocampus, the center of emotion and memory. Delirium could be caused by many different problems, be it a decrease in blood flow to various parts of the brain, a brain lesion, or derangements of neurotransmitters.¹⁶ It may not be obvious how dementia is related to delirium, but dementia is the strongest risk factor of delirium with the primary deficit being attention. In regard to neuroplasticity, the brain can change through activity-based neuroplasticity through the response of experience or activity.

There are two ways that the brain can be modified. These include plasticity of existing neurons or neurogenesis. The use of activity-based neuroplasticity is continued through adulthood when neurogenesis begins to cease. Activities to help develop the brain include learning and problem-solving challenges, exercise, and sensory stimulation. Engaging in these activities are beneficial for individuals with dementia to help engage their brain to produce positive behavioral and cognitive change. Specifically, long-term regular exercise shows benefit to reducing dementia progression.¹⁹The sustained exercise that is being defined is aerobic exercise that increases the heart rate and need for oxygen lasting at least 20-30 minutes per session. This type of exercise is known as cardiovascular fitness and can be completed through walking, running, home activities, gym, or health club routines.¹⁹ Analysis of 29 randomized controlled trials indicated that aerobic exercise significantly improved cortical connectivity, in the regions associated with memory.¹⁹²² Significant improvements were also evident when patients were given cognitive tasks. Sustained exercise in patients with Alzheimer’s disease also saw a reduction in the risk of morality.¹⁹ Exercise is an easy task that can be completed by individual’s suffering from AD with the benefits helping their mind and creation of a healthier body.
Exercise has shown promising improvements to the cognitive effects of dementia, but some patients are unable to engage in these activities due to health problems. Alzheimer’s disease is one of the most damaging forms of dementia and is very common in an aging population where physical exercise may not be feasible due to barriers like back pain, sore knees, heart conditions, or lung disorders. The current care for Alzheimer’s disease is cholinergic and glutamatergic drugs which contain many adverse side effects.²⁴ Instead of the use of exercise, neuroplastic treatment through repetitive non-invasive brain stimulation can help slow down cognitive decline and enhance neuronal activity.
Repetitive transcranial magnetic stimulation (rTMS) is a noninvasive brain stimulation method to promote neuroplastic changes in patients with Alzheimer’s disease.²⁴ rTMS is a painless procedure that generates a magnetic pulse through a stimulated coil that is placed on a patients head.²⁶ A transient electric field is produced underneath the surface that causes depolarization of the neurons in the cerebral cortex.²⁶ Patients who have mood disorders and depression can be influenced by rTMS to repair these processes. Specifically, long term potentiation (LTP) is the best target for this treatment since it is linked to cognitive function and is the most widely proposed mechanism for memory storage.²⁶²⁴ LTP involves the strengthening of neuronal synapses leading to long-lasting transmission in neuronal signals. In the early stages of Alzheimer’s disease, cortical plasticity is impaired, affecting one’s verbal memory. The use of rTMS on LTP cortical plasticity could help to reduce the progression of the disease.²⁴ The best course of treatment may involve long term use of these methods to target the prefrontal cortex for the improvement of cognitive function.²⁴ With research continuing in this area, the full effects of this treatment are still unknown, but the results are promising. Through this research, it is also evident that Alzheimer’s disease does not have to be targeted specifically to improve cognitive function. If patients are diagnosed with other neurological conditions, targeting these conditions could have a positive impact on the cognitive problems they may be experiencing.
A study that went in depth on the use of rTMS treatment along with cognitive training (CT) found improvement of AD symptoms that was associated with disease progression and level of education. Adding rTMS with cognitive training is used to enhance neuroplasticity by combining exogenous and endogenous stimulation.²⁶ In this study, only the left dorsolateral prefrontal cortex, involved in executive function and control of cognitive processes, was stimulated and a face-name memory test was conducted.²⁶³⁴ They conducted the research through two groups, one where patients received rTMS with CT and one where patients only received CT.²⁶ In the patients who received the rTMS, it was administered before cognitive training to “prime” their brain to increase the efficiency of face-name associative memory.²⁶ The results of the face-name memory tests are shown in Figure 3 after 4 weeks of treatment was completed.

The results from the study showed CT sessions alone were effective in improving face-name associative memory along with an enhancement in improvement with rTMS.²⁶ Nonetheless, this improvement was associated with the severity of the disease and education, thus limiting the effect that the treatment could have on patients.²⁶ Based on these results, if AD is diagnosed early, then CT treatment with rTMS is a viable option to replace the use of medication. To achieve the best results during treatment, the study advised to propose treatment with this method as early as possible before neuronal loss is seen.²⁶ This method can cause neuroplastic long term potentiation changes in the brain, reducing the life changing effects of AD, but there are limits to this method. It is heavily dependent on the stage of AD and the amount of education the patient has. Having a higher education allows individuals to link new knowledge with stored knowledge which can demonstrate a faster treatment of symptoms and act against AD progression. This does not mean treatment cannot be conducted on people with less education, the results may not be as evident.

The rise of neuroplasticity as treatment for dementia is showing promising results by increasing cognitive ability. Through long term exercise or stimulation of neuronal pathways with rTMS to initiate neuroplasticity in the brain, patients can find relief from the life changing conditions of their disease. Even though dementia is not yet reversible, patients whose memory and cognitive ability is declining can still lead more fulfilling lives than they would have been able to otherwise. Continued research is still being conducted on the benefits of neuroplasticity for treatment, but current results are promising towards the field of neurodegenerative diseases.