A Clinical Guide to Alzheimer's Disease

A Clinical Guide to Alzheimer's Disease

Author: Min Geraets | BNatMed | Naturopath & Medical Herbalist

For many individuals, alterations to memory and cognition emerge gradually, often dismissed initially as normal ageing.  A misplaced item, a forgotten name, a missed appointment.  For some, these changes mark the beginning of a progressive and life-altering neurological condition.

With Alzheimer’s disease (AD), cognitive decline is not merely a benign feature of ageing.  It is a complex, evolving disorder that reshapes memory, identity and functional dependence over time.

Individuals with AD and their families may describe a slow unravelling: increasing forgetfulness, difficulty with language, disorientation and subtle personality changes.  In the early stages, insight may remain intact, often accompanied by anxiety or frustration.  As the disease progresses, this awareness diminishes, and care needs intensify.

This trajectory is one of the most clinically important features of AD, yet early signs are frequently overlooked or attributed to stress, burnout or ageing.

Beyond memory loss: A multifactorial neurodegenerative disorder

AD is the most common cause of dementia, accounting for approximately 60-70% of cases.  It is characterised by progressive cognitive decline, functional impairment and behavioural changes.1

Epidemiological data indicate that age is the most significant risk factor for AD, with prevalence increasing exponentially from 3% at age 65 to 32% at age 85.  More than 50 million people are affected by AD worldwide, which is estimated to increase by three times (approx. 152.8 million) by 2050.1

Historically, AD has been defined by two pathological hallmarks:

  • Amyloid-β plaque formation
  • Intracellular tau protein neurofibrillary tangles (NFTs).1

While these remain central to diagnosis, contemporary research has expanded understanding of AD as a multifactorial condition involving:

  • Chronic neuroinflammation
  • Oxidative stress
  • Mitochondrial dysfunction
  • Synaptic degeneration
  • Vascular impairment 
  • Gut dysbiosis
  • Metabolic dysregulation.1,2

These processes interact dynamically.  For example, metabolic dysfunction can promote inflammation, which can alter the microbiome and increase blood-brain barrier (BBB) permeability.  The clinical implication is clear: targeting a single pathway is insufficient, multimodal intervention is required.

This broader framework represents a critical opportunity for Naturopaths.  Many of the underlying mechanisms are modifiable long before clinical symptoms emerge, positioning integrative care at the forefront of prevention and early intervention.

Clinical presentation and diagnostic framework 

AD presents along a continuum, from preclinical changes to mild cognitive impairment (MCI) and ultimately, dementia.

Early symptoms include:

  • Short-term memory impairment 
  • Difficulty finding words 
  • Reduced executive function
  • Subtle mood or personality changes
  • Withdrawal from social engagements 
  • Visuospatial problems and gait impairment.3

As the disease progresses:

  • Disorientation and confusion increase
  • Language and communication decline 
  • Behavioural symptoms (agitation, apathy, depression) emerge 
  • Activities of daily living become impaired.3

The diagnostic process for AD can be divided into the following stages:

  • Stage 1: The initial assessment should focus on clinical history, a family members perspective, current medications and lifestyle factors (smoking, alcohol, exercise).3,4
  • Stage 2: If AD is suspected, a cognitive assessment will take place using the Mini-ACE (Mini-Addenbrooke's Cognitive Examination) test.  There are limitations (potential biases relating to the persons education level, language or cultural identity) to cognitive testing, and they should, therefore, not be used in isolation.4
  • Stage 3: Referral to secondary care may be indicated if there is diagnostic or management uncertainty.  This is where functional assessments such as neuroimaging (MRI, CT, or PET scans) and biomarkers (amyloid-β peptides and tau proteins in cerebral spinal fluid) may be ordered.3,4

Differential diagnosis is critical and includes:

  • Depression or delirium
  • Vitamin B1, B12 or folate deficiency
  • Thyroid dysfunction
  • Medication effects (anticholinergic medicines, opioids, psychotropic medicines, steroids)
  • Alcohol or drug misuse 
  • Structural brain disease
  • Neurological infections (HIV or syphilis)
  • Hearing or vision impairments
  • Sleep apnoea.4

Clinical assessment: A naturopathic framework 

For naturopathic practitioners, early identification is key.  Consider:

  • Family history (APOE genotype where available)
  • Metabolic markers (HbA1c, fasting insulin and glucose)
  • Nutritional status (vitamin B1, B12, folate, omega-3 and choline intake)
  • Lifestyle factors (physical activity, sleep patterns, alcohol intake)
  • Cardiometabolic health (blood pressure, lipid profile)
  • Inflammatory markers (CRP, cytokines)
  • Gastrointestinal health (bloating, gut dysbiosis, bowel habits)
  • Oral health status
  • Cognitive screening tools (early MCI detection using Mini-ACE test)
  • Psychosocial context (support systems, caregiver capacity, mental health status).

Pathophysiology: Integrating emerging mechanisms 

Amyloid-β and tau pathology 

Amyloid-β accumulation is thought to initiate a cascade of neurodegenerative processes, including:

  • Synaptic damage 
  • Mitochondrial dysfunction
  • Neuroinflammation
  • Oxidative damage.5

Tau proteins, when hyperphosphorylated, form NFTs that disrupt neuronal transport systems and contribute to cell dealth.5

While amyloid and tau pathology remain at the centre of AD research, they fail to completely explain the disease severity and complexity, highlighting the importance of considering additional mechanisms.

Neuroinflammation and immune dysregulation 

Chronic neuroinflammation is now recognised as a primary driver of AD progression.

Microglial activation, while initially protective, can become dysregulated, leading to:

  • Sustained release of pro-inflammatory cytokines 
  • Neuronal damage
  • Accelerates amyloid-β deposition 
  • Impaired clearance of amyloid-β plaques.5

Clinically, this raises important considerations:

  • Are there systemic drivers of inflammation present (diet, gut health, chronic infection)?
  • Is there coexisting metabolic or autoimmune dysfunction?
  • Targeting inflammation may represent a key therapeutic avenue in integrative care.

Insulin resistance and metabolic dysfunction

AD has been increasingly described as 'type 3 diabetes' due to impaired insulin signalling and glucose metabolism deficits in the brain.  The brain is highly metabolically active, requiring a constant supply of glucose to function properly.  It does not store glucose in significant amounts, meaning it depends on insulin signalling to regulate glucose uptake, energy production and cellular repair.6 

Insulin resistance contributes to:

  • Reduced glucose uptake in neurons 
  • Increased oxidative stress 
  • Neuroinflammation
  • Damaged synaptic plasticity and integrity 
  • Enhanced amyloid-β and tau accumulation.6

Recognising metabolic health as a modifiable risk factor may open new opportunities to reduce the onset and progression of cognitive decline, potentially transforming current approaches to AD prevention and care.  From a clinical perspective, strategies that enhance insulin sensitivity and maintain stable blood glucose levels may provide a promising avenue for reducing the impact of AD.

Oxidative stress and mitochondrial dysfunction 

Neurons are highly energy-dependent cells and are particularly vulnerable to oxidative damage, which contributes to cognitive decline.  In AD:

  • Mitochondrial function declines, reducing the brain's ability to generate energy efficiently 
  • Reactive oxidative species (ROS) increase
  • Cellular repair mechanisms become impaired.5 

Mitochondrial dysfunction and oxidative stress damage lipids, proteins, and DNA, accelerating neurodegeneration and cognitive decline.  Oxidative stress may also contribute to the formation of amyloid-β plaques and NFTs, further amplifying progression of AD.5  From a clinical perspective, antioxidant therapies and strategies that support mitochondrial health - including dietary, herbal and supplemental interventions - are important considerations in the management of the disease.

Synaptic degeneration 

Synaptic dysfunction and neurotransmitter imbalance are key features of AD pathology and contribute significantly to cognitive decline.  Synapses are essential for communication between neurons.  In AD:

  • Amyloid-β accumulation and NFTs damage synapses and impair neuronal communication
  • Neurotransmitter release and synaptic plasticity become disrupted 
  • Acetylcholine levels decline due to degeneration of cholinergic neurons.5 

Amyloid-β aggregates interfere with synaptic signalling by reducing density and impairing the ability of synapses to strengthen and adapt in response to stimuli.  This contributes to progressive memory impairment and loss of cognitive function.  Dysfunction in glutamate neurotransmission may also lead to excitotoxicity, causing neuronal injury and cell death.  Alterations in dopaminergic, serotonergic and noradrenergic systems can further affect mood, behaviour and cognition.5 

Synaptic dysfunction is also associated with disruption of proteins involved in synaptic structure and communication, including synaptic vesicle proteins and postsynaptic density proteins.  Impaired neuronal signalling compromises synaptic stability and accelerates neurodegeneration.5 

From a clinical perspective, supporting synaptic health may include strategies that reduce neuroinflammation and oxidative stress, optimise nutrient status and support healthy neurotransmitter synthesis and signalling.  Nutrients such as choline, omega-3 fatty acids and B vitamins, alongside dietary and lifestyle interventions that support cognitive function and metabolic health, may be relevant adjunctive considerations in client care.

Gut-brain axis and microbiome

Emerging research suggests that gut microbiota may influence AD through:

  • Immune modulation
  • Inflammatory signalling and cytokine production
  • Microbial metabolites (SCFAs) influencing neuronal function and amyloid-β aggregation
  • Neurotransmitter signalling pathways 
  • Production of neuroactive compounds.1

Gut dysbiosis has been associated with increased intestinal permeability and systemic inflammation, both of which may alter neurotransmission, disrupt the blood-brain barrier, impact amyloid-β pathology and contribute to neurodegenerative processes.1

Conversely, AD is associated with:

  • Reduced microbial diversity 
  • Depletion of beneficial SCFA-producing bacteria
  • Increased pro-inflammatory species
  • Elevated lipopolysaccharide (LPS) burden.7

This bi-directional relationship outlines how dysbiosis is not merely a consequence of disease, it can also be a driver of pathology.  Most importantly, it is modifiable.  This opens potential therapeutic avenues involving dietary modulation, targeted pre-and pro-biotics and gut repair strategies.

The oral microbiome-brain connection 

Emerging evidence supports a strong connection between oral health and brain health.  Consistent with the oral microbiome paradigm:

  • Periodontal pathogens have been identified in the brains of individuals with AD
  • Chronic oral inflammation may contribute to systemic inflammatory load
  • Pro-inflammatory alterations in the oral microbiome have also been observed in individuals with MCI, a condition that can precede AD diagnosis by many years.8

These findings suggest that oral microbiome changes may occur well before the clinical onset of AD, highlighting the importance of early prevention and the promotion of healthy oral hygiene habits.

Vascular contributions 

Cerebral blood flow and vascular integrity play a significant role in cognitive function.  Hypertension, atherosclerosis and endothelial dysfunction can:

  • Reduce oxygen and nutrient delivery to the brain 
  • Exacerbate amyloid-β deposition 
  • Accelerate cognitive decline.9

These findings reinforce the importance of cardiovascular health in AD prevention and management.

Therapeutic approaches 

1. Dietary strategies 

  • Mediterranean diet (MD): Emphasising high intake of vegetables, fruits and legumes; olive oil as the primary fat source; moderate fish consumption; and low intake of refined sugars and processed foods has been associated with an 11-30% reduction in the risk of age-related cognitive disorders, including AD.9  The MD improves cognitive function through several mechanisms including reduced pro-inflammatory signalling, improved insulin sensitivity and increased microbial diversity.10  A 2018 study involving middle-aged, cognitively normal participants adherence to the MD may slow AD progression by 1.5 to 3.5 years.11
  • Ketogenic diet: Characterised by high fat, very low carbohydrate and moderate protein intake, the ketogenic diet promotes the production of ketone bodies as an alternative source of energy for the brain.  Emerging evidence suggests the ketogenic diet may improve quality of life and daily functioning in people with AD, where impaired brain glucose metabolism is a key feature.  Proposed mechanisms include enhanced brain energy metabolism, reduced neuroinflammation and improved mitochondrial function.12  This diet is not without limitations, which include difficulties with long-term adherence, unwanted weight loss or nutrient deficiencies in older adults. 

2. Nutritional supplementation 

Prevention

  • Choline (350-550 mg/day): Plays an essential role in cognition and serves as a precursor to phosphatidylcholine, a compound critical for inhibiting amyloid-β aggregation and protecting against neuronal damage.13  Recent clinical studies suggest that a moderate to high daily intake of 330-550 mg is associated with a lower risk of dementia and improved cognitive performance.14,15
  • Omega-3 fatty acids (EPA/DHA 1-2 g/day): Clinical research has found that adequate daily intake is significantly associated with a lower risk of AD and may support treatment in individuals with cognitive impairment.  DHA helps maintain neuronal integrity and provides neuroprotective effects by inhibiting tau phosphorylation.  EPA is required to modulate inflammation and immune signalling associated with AD pathogenesis.16
  • Vitamin B complex (B6, B12, folate): Essential for homocysteine regulation and cognitive function.  Elevated homocysteine and low levels of folate and B12 are associated with increased AD risk.17
  • Vitamin D (800-4000 IU/day): Deficiency has been linked to cognitive decline, neurodegeneration and an increased risk of AD.17,18
  • Probiotics (Bacteroides, Bifidobacterium, Lactobacillus): Emerging evidence suggests that probiotic-induced modulation of the gut microbiota may improve cognitive function, through interactions along the gut-brain axis.19  Genera such as Bacteroides, Bifidobacterium and Lactobacillus are known to produce GABA.  As an inhibitory neurotransmitter, GABA is vital for cognitive processes including attention, memory and learning.20

Management 

  • Acetyl-L-carnitine (1.5-3 g/day): Clinical research shows daily consumption for 3-12 months may slow the rate of AD progression, improve memory, some measures of cognitive function and behavioural performance.  It is more likely to show benefit in those with early-onset AD and those with a faster rate of disease progression and mental decline.21,22
  • Phosphatidylserine (300-400 mg/day): Plays a key role in maintaining cell membrane stability and is essential for neuronal energy production and communication.23  Bovine-derived phosphatidylserine appears to improve cognitive function and behaviour in AD patients when used up to 16 weeks, although the benefits appeared to stop after this period during the treatment period of 6 months.24,25 It is unclear if plant-derived phosphatidylserine is effective.

3. Herbal medicine 

  • Ashwagandha (Withania somnifera) modulates stress hormones, particularly cortisol, which is often elevated in neurodegenerative conditions.  It has also been shown to suppress the activation of pro-inflammatory enzymes, thereby reducing neuroinflammation and providing neuroprotective effects.  In addition, withanolides derived from Ashwagandha attenuate tau hyperphosphorylation by inhibiting the activity of tau kinases such as glycogen synthase and kinase (GSK)-3β and cyclin-dependent kinase 5 (CDK5).26
  • Bacopa (Bacopa monnieri) has been clinically shown to improve memory, attention and cognitive performance in those experiencing cognitive decline.  It works by enhancing acetylcholine signalling to improve neuronal communication.  Its antioxidant properties protect neurons from oxidative stress, which is a key factor in AD pathogenesis.26
  • Ginkgo (Ginkgo biloba) improves cerebral blood flow by inhibiting platelet-activating factor (PAF), helping to ensure optimal oxygen and nutrient delivery to neurons.  It may enhance cognition and working memory by reducing neuroinflammation and inflammatory markers.  Its constituents ginkgolides, kaempferol and quercetin, also exert potent antioxidant effects that help protect neurons from oxidative damage.26
  • Gotu kola (Centella asiatica) is a circulatory stimulant that improves blood flow to the brain.  It has also been shown to promote neuronal regeneration and synaptic connectivity by increasing the expression of brain-derived neurotrophic factor (BDNF).  These effects may help improve cognitive resilience and synaptic signalling, which are essential for memory consolidation.26
  • Green tea (Camellia sinensis) is a potent antioxidant that has displayed regulatory effects on mitochondrial function.  Epigallocatechin gallate (EGCG), the primary catechin found in green tea, is believed to be the primary factor in attenuating oxidative stress through metal ion chelation and neuroprotective activity, including the inhibition of amyloid aggregation.27  Furthermore, EGCG has been shown to disestablish NFTs in vitro.28
  • Korean ginseng (Panax ginseng) demonstrates neuroprotective effects through its primary constituent, ginsenoside Rb1 and Rg1, by protecting against amyloid-β induced cytotoxicity and deposition and reducing hyperphosphorylated tau levels in vitro.29,30  In addition, it has been shown to reduce neuroinflammation and oxidative stress by lowering levels of reactive oxidative species, TNF-α and IL-6.29
  • Lion's mane (Hericium erinaceus) contains bioactive compounds, particularly hericenones and erinacines, that can cross the BBB and stimulate nerve growth factor (NGF) synthesis, exerting notable neuroprotective properties.  Lion's mane supports the growth, maintenance and repair of neurons, especially during ageing and neurodegenerative conditions such as AD.  Preclinical studies and early clinical trials also suggest Lion's mane may benefit individuals with MCI and mood disorders.31
  • Saffron (Crocus sativus) exhibits neuroprotective properties that support cognitive function and may be beneficial in neurodegenerative conditions including AD.  Research suggests Saffron can inhibit the aggregation and deposition of amyloid-β.  Additionally, its antioxidant effects help protect neurons from oxidative stress and may slow cognitive decline.32
  • Sage (Salvia officinalis) demonstrates memory and cognitive enhancing effects, which are primarily attributed to its cholinesterase inhibitory activity, the enzyme responsible for catabolising acetylcholine.26,33
  • Turmeric (Curcuma longa) is a potent anti-inflammatory and antioxidant that has been clinically shown to protect against LPS-induced damage and neuroinflammation.  Its primary active constituent, curcumin, can cross the BBB due to its lipophilic properties, enabling it to bind to amyloid deposits.  Curcumin has also been shown to reduce amyloid-β plaque formation by modulating amyloid precursor protein activity and suppressing mitochondrial-mediated neuronal death.34 

4. Lifestyle medicine 

  • Physical activity: Regular exercise is one of the strongest protective factors against cognitive decline.  It can slow the progression of neurodegenerative diseases by reducing amyloid-β accumulation, oxidative stress, neuroinflammation and neuronal cell death.  It also supports neurogenesis by increasing BDNF levels.  In addition, exercise improves insulin sensitivity and cardiovascular health, helping to regulate metabolic and vascular factors involved in AD pathogenesis.  Clinical studies have determined both aerobic and resistance training to be beneficial, particularly when combined.35,36
  • Sleep optimisation: Poor sleep is associated with increased accumulation of amyloid-β and fragmented tau proteins, as impaired glymphatic system function compromises the clearance of metabolic waste.37  Focus on sleep hygiene practices, circadian rhythm regulation and addressing sleep apnoea where appropriate.
  • Stress management: Current evidence suggests that chronic stress may contribute to AD pathogenesis through its association with neuroinflammation, hippocampal atrophy, cortisol dysregulation and alterations in the microbiome.38  Focus on stress management strategies including meditation and mindfulness practices, yoga and tai-chi.
  • Cognitive reserve: This is built by keeping the brain active throughout a person's lifetime and is therefore more clinically relevant to the prevention of AD rather than its management.  Individuals with greater cognitive reserve can tolerate more neurodegenerative change before experiencing difficulties with everyday functioning.39  Learning new skills, engaging in diverse social interactions and participating in mentally stimulating activities help increase cognitive reserve by enhancing neuroplasticity and building a functional reserve that may protect against future neuronal loss.40

5. Pharmacological interventions (collaborative care)

Conventional treatments include:

  • Acetylcholinesterase inhibitors (donepezil, rivastigmine, galantamine)
  • NMDA receptor antagonists (memantine).4

These may provide symptomatic relief but do not halt disease progression.

Collaborative care is essential to ensure safe and comprehensive management.

Emerging directions: Where the research is heading 

Research into AD is rapidly evolving.  Key areas include:

  • Anti-amyloid therapies: Monoclonal antibodies such as lecanemab and donanemab that target amyloid-β are now demonstrating modest slowing of cognitive decline in early AD and are shaping the first generation of disease-modifying therapies.41
  • Faecal microbiota transplantation (FMT): FMT is being investigated as a potential way to modify the gut-brain axis and reduce neuroinflammation, although evidence remains preliminary and clinical efficacy has not yet been established.42
  • Neuroinflammation modulation: Therapies targeting microglial activation, inflammatory signalling, and immune pathways are emerging as important complements to amyloid-β and tau-focused treatments.43
  • Metabolic therapies: Research into ketogenic diets, insulin-sensitising agents, mitochondrial function, and metabolic dysfunction reflects growing recognition that impaired cerebral energy metabolism contributes to AD pathology.44
  • Microbiome research: Increasing evidence links alterations in the gut microbiome with AD progression, prompting investigation into probiotics, dietary interventions, and microbiome-targeted therapies.45
  • Precision medicine: Advances in blood-based biomarkers, genetics, and multimodal profiling are enabling earlier diagnosis and more personalised therapeutic approaches.46

These developments reflect a broader shift toward earlier detection, combination therapies, and personalised intervention strategies in AD management.

Key takeaways

  • Multifactorial disease: AD is not solely a neurological disorder but also involves inflammation, metabolic dysfunction, oxidative stress, vascular impairment and the microbiome.
  • Early intervention is critical: Addressing modifiable risk factors may help delay cognitive decline and slow disease progression.  Naturopaths are well-positioned to support AD with therapeutic strategies that target root causes and modify disease trajectory.
  • Lifestyle medicine is foundational: Nutrition, regular physical activity, sleep, stress management and cognitive enhancement all play important roles in prevention and management.
  • Gut-brin and oral-brain connections are emerging: Dysbiosis, intestinal permeability and poor oral health may contribute to neuroinflammation and cognitive decline.
  • Building cognitive reserve throughout one's lifetime is essential: A large cognitive reserve is a significant protective factor against neurodegenerative change.
  • Integrative therapies may offer support: Nutritional supplementation and herbal medicines may complement conventional treatment by targeting neuronal function, inflammation and oxidative stress.

References 

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