What is Alzheimer’s disease?
Alzheimer’s disease is a progressive brain disorder that damages memory, thinking, and capacity for daily function. It develops slowly and worsens over time.
Key features of Alzheimer’s disease include:
- gradual loss of cognitive function
- reduced ability to manage tasks and self-care
- changes in behaviour and mood
Disease progression
- Early stage (mild cognitive impairment) – subtle memory and thinking changes
- Moderate stage – increased memory loss and confusion, impaired language, orientation, and decision-making
- Advanced stage – severe cognitive decline, requires dependence on others for basic daily activities
- Changes in brain function develop decades before symptoms become noticeable
Alzheimer’s disease is now understood as a multifactorial condition, arising from interacting metabolic, vascular, inflammatory, genetic, and lifestyle-related influences as opposed to a single cause.
Medical standard of care
The medical approach focuses on diagnosis and symptom management. It does not reverse or stop disease progression.
Standard medical treatment goals include:
- maintaining cognitive function
- slowing symptom progression
- supporting safety and daily function
Commonly used medications:
- Donepezil
- Rivastigmine
- Galantamine
- Memantine
Currently used medications:
- achieve modest symptomatic relief or slight slowing of decline (Birks, 2006; McShane et al., 2019; van Dyck et al., 2023)
- do not restore neuronal function or reverse established damage (What Happens to the Brain in Alzheimer’s Disease?, 2024; van Dyck et al., 2023)
- carry meaningful risks, which can cause brain swelling or bleeding in a subset of patients (van Dyck et al., 2023)
Typically, management also includes support for mood and behavioural changes, caregiver education, safety planning, and long-term care planning as the disease advances.
Why consider an orthomolecular approach?
Alzheimer’s disease can be caused by many different factors, as shown by both research and clinical experience. The medical standard of care addresses only some of these factors.
An orthomolecular approach:
- identifies the drivers and causes of Alzheimer’s disease and focuses on addressing them
- addresses the specific biological factors that may be affecting each individual
- works WITH the body to restore balance and normal function, and considers the person with the condition versus just the condition
- addresses nutrient depletions and other factors that promote Alzheimer’s disease
- can be done SAFELY in conjunction with most medical interventions
Mechanisms of Alzheimer’s disease progression
Alzheimer’s disease progresses through interacting biological processes that damage brain cells over time. These processes reinforce each other and drive ongoing decline.
1. Protein mis-processing and impaired clearance
Damaged proteins build up and disrupt cell function
- Impaired protein handling – Improper protein folding and repair results in accumulation of damaged proteins
- Amyloid and tau accumulation – Misfolded proteins form plaques and tangles that damage synapses (the junctions between brain cells where they pass signals to each other), disrupting communication between brain cells and eventually leading to cell death.
- Reduced glymphatic clearance – Decreased cerebrospinal fluid–mediated waste clearance limits removal of metabolic byproducts, particularly during sleep
2. Metabolic and energy failure
Brain cells cannot produce enough energy
- Brain insulin resistance – Brain cells don’t respond properly to insulin resulting in reduced glucose (sugar) uptake into neurons, reducing the ability to produce energy
- Mitochondrial dysfunction – Impaired production of the cellular energy molecule adenosine triphosphate (ATP), and increased production of reactive oxygen species (ROS) – which contribute to cellular stress
- Brain energy deficit – Neurons receive or utilize insufficient metabolic fuel (glucose and/or ketones) to function normally
- Oxidative stress – Excess reactive oxygen species overwhelm antioxidant defenses, damaging lipids, proteins, and nucleic acids
- Glycation and AGE accumulation – Glycation damages proteins and lipids, altering structure, signalling, and receptor function, and impairing amyloid clearance
3. Barrier and vascular dysfunction
Loss of protection and reduced nutrient delivery
- Reduced cerebral blood flow – Decreased cerebral blood supply limits the delivery of oxygen and essential nutrients required for neuronal function and maintenance
- Impaired microcirculation and fluid flow – Increased viscosity and stagnation at the capillary level slows blood movement, reducing distribution of nutrients and limiting waste removal
- Blood–brain barrier (BBB) breakdown – Increased permeability of the barrier allows circulating toxins, immune mediators, and inflammatory signals to enter brain tissue
4. Neuro-inflammation and Immune Activation
The immune system stays “switched on” contributing to progressive injury
- Microglial activation – Persistent activation of immune cells causes the ongoing release of inflammatory mediators, instead of resolution of tissue injury
- Cytokine dysregulation – Immune signalling molecules become dysregulated, amplifying inflammation and slowing repair
- Chronic inflammation – Sustained low-grade inflammatory signalling disrupts communication between brain cells and promotes neuronal damage.
- Synaptic downscaling / protective pruning – As an adaptive response, the brain reduces the activity of, and number of synapses to limit damage caused by excessive stimulation of neurons. Excessive pruning leads to loss of synaptic connections and contributes to cognitive decline.
5. Impaired repair and regeneration
The brain shifts from repair to breakdown
- Reduced availability of growth and repair molecules including hormones, nutrients, and neurotrophic factors shifts the brain from a “build and maintain” state toward breakdown. This results in decreased neuronal maintenance and increased vulnerability to neurodegeneration.
A deeper look: how the mechanisms interact
Alzheimer’s disease emerges from a network of interconnected mechanisms that reinforce one another over time.
Metabolic dysfunction and protein pathology
- Energy failure increases oxidative stress, promoting the production of amyloid-beta from APP
- Oxidative damage to lipids can increase Aβ production
- Aβ and tau directly impair mitochondrial function
- Declining ATP availability limits cellular repair and protein clearance
- Cells respond to sustained stress by down-regulating metabolism and repair
- Synaptic downscaling reduces neuronal activity and connectivity as an adaptive response
Protein accumulation and inflammation
- Chronic microglial activation leads to cytokine release and ROS production
- Inflammatory mediators promote further neuronal damage and protein misfolding
- Aβ and tau act as danger signals (danger-associated molecular patterns, DAMPs)
Barrier dysfunction, inflammation and amyloid burden
- BBB breakdown allows entry of inflammatory molecules and toxins (Lam et al., 2016)
- Increased RAGE-mediated transport raises brain Aβ levels (Yoon et al., 2023)
- Inflammation further damages the BBB, increasing permeability
- Impaired Aβ clearance across the BBB accelerates accumulation
- Impaired microcirculation and fluid dynamics reduce oxygen and nutrient delivery while limiting waste removal, contributing to amyloid accumulation and neuroinflammation
Impaired clearance and protein accumulation
- Dysfunctional glymphatic flow reduces removal of Aβ and metabolites (Quevedo et al., 2023)
- Impaired autophagy (the cell’s process of breaking down and recycling damaged proteins and cellular components) prevents degradation of misfolded proteins (Vinuesa et al., 2021)
- Accumulated proteins disrupt cellular function and signalling
- Protein buildup further impairs clearance pathways
System-wide interactions (brain–body connection)
- Peripheral tissues (e.g., liver, pancreas) can produce Aβ that enters circulation (Chandrashekar et al., 2023)
- Circulating Aβ can cross the BBB and contribute to brain pathology (Kauwe & Tracy, 2021)
- Systemic metabolic dysfunction influences brain energy metabolism
- Peripheral inflammation and immune signals can amplify neuroinflammation
- Systemic deficiencies in hormones, nutrients, and trophic signals reduce neuronal repair and regeneration capacity, contributing to progressive neurodegeneration
Each Alzheimer’s disease mechanism worsens the others.
This cycle highlights why addressing a single factor is often insufficient.
Metabolic / energy failure
↓
Protein misprocessing and accumulation
↓
Neuroinflammation
↓
Barrier and vascular dysfunction
↓
Impaired clearance (glymphatic + autophagy)
↓
Synaptic dysfunction and network breakdown
↓
Cellular stress and impaired repair
↓
Further metabolic stress and cellular injury
The cycle repeats and amplifies
These interconnected mechanisms help explain how Alzheimer’s disease develops and progresses.
The Contributing Factors, and Orthomolecular Intervention sections explore the underlying factors that drive these processes and how targeted orthomolecular strategies may help address them.
