Alzheimer’s Disease

Alzheimer’s disease (AD) is a slowly progressive dementia characterized by cognitive decline and behavioral changes. Pathological changes in the brain include atrophy of the cerebral cortex (particularly in the temporal and temporoparietal lobes), the presence of neurofibrillary tangles and senile (beta-amyloid) plaques, a loss of cholinergic neurons in the brain, and reduced activity of choline acetyltransferase (the enzyme responsible for acetylcholine production) in the cerebral cortex and hippocampus. Pathogenesis is not fully understood but involves neurotoxicity, inflammation, and, likely, apoptosis.

The disease typically progresses from mild memory impairment to severe cognitive loss with personality and behavioral changes. The patient often experiences language problems, particularly with generation of nouns (dysnomia), and spatial disorientation is common. AD reduces life expectancy,[1] and is the sixth leading cause of death among US adults.[2]

Risk Factors

AD is associated with the following:

Older age. It has been estimated that in 2020, about 6 million people were living with clinical AD in the US, with a projected increase to just under 14 million in 2060.[3]

Family history. Risk is inversely proportional to the age of onset in a first-degree relative.

Genetics. AD is associated with the presence of the epsilon 4 allele of apolipoprotein E. Other genetic abnormalities (particularly with the presenilin and amyloid precursor protein genes) place some individuals at high risk of early-onset AD. Trisomy 21 is also associated with increased risk.[4]

Hypercholesterolemia. Elevated LDL cholesterol levels are independently associated with an increased AD risk.[5] It has been proposed that elevated cholesterol causes deposition of beta-amyloid plaques in the brain.

Herpesviruses. Herpesviruses appear to play a causal role in some cases of AD. Herpes simplex virus 1 is acquired early in life by most people and remains lifelong in the trigeminal ganglia. As immune defenses flag later in life, the virus makes its way to the brain.[6][7] In cultured human brain cells, the virus causes production of beta-amyloid and altered tau proteins.[8][9][10] In well-controlled observational studies, the use of ordinary antivirals—acyclovir, valacyclovir, or others—is associated with significantly reduced AD risk, particularly among individuals carrying the APOE4 allele.[11][12][13]

Lithium deficiency. Studies in diverse geographic regions have shown that low lithium levels in drinking water are associated with higher AD rates.[14][15][16][17] In studies of human brain tissue, lithium has been shown to be notably absent in the brain areas affected by AD, apparently sequestered in amyloid plaques, which act like sponges, soaking up lithium and depriving brain cells that need it.[18]

Excess body weight. Excess weight before age 65 is associated with increased risk of AD.[19][20]

Sedentary lifestyle. Observational studies and clinical trials show that regular aerobic exercise (e.g., a 40-minute walk 3 times per week) reduces the risk for developing dementia and may reverse shrinkage in the hippocampus and other brain structures.[21][22][23][24]

Hypertension, declining blood pressure over time, cerebrovascular and cardiovascular disease, diabetes, smoking, and persistently elevated alcohol use.[4] All these factors are associated with cerebral atrophy. Excess body weight may exacerbate these factors or lead to cerebral atrophy directly.[25]

Elevated homocysteine and metabolic syndrome may also increase risk.[26][27]

Brain trauma. A history of traumatic brain injury may be associated with development of AD.[28]

Poor sleep. Reduced sleep quality, sleep problems, and daytime sleepiness are associated with altered AD biomarkers (beta amyloid, tau, and inflammation) in cerebrospinal fluid.[29]

Diagnosis

Diagnosis

Current evaluation of the patient with suspected AD focuses on identifying potentially reversible disorders that can produce cognitive deficits. The diagnosis of AD is made through the recognition of clinical features and presenting symptoms. However, a definitive diagnosis is not possible in normal clinical practice, as pathologic findings cannot be demonstrated except by autopsy.

The Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-5) recognizes 2 cognitive syndromes: mild neurocognitive impairment and major neurocognitive impairment. The latter includes AD and other types of neurodegenerative dementias. AD is diagnosed through a multi-step process that integrates clinical evaluation, biomarker testing, and neuroimaging. Initial assessment involves a detailed patient and caregiver history, cognitive testing (e.g., memory and executive function assessments), and physical examinations to rule out other causes of impairment.[30] Biomarkers, such as amyloid positron emission tomography (PET), cerebrospinal fluid (CSF) analysis for amyloid-β and tau proteins, and plasma biomarkers like phosphorylated tau 217, are increasingly used to detect AD neuropathologic changes even in asymptomatic stages.[31] Advanced neuroimaging techniques, including MRI and tau PET, help evaluate structural brain changes and disease progression, while also differentiating AD from other dementias. National Institute on Aging and the Alzheimer’s Association guidelines published in 2018 emphasize a biological definition of AD, prioritizing biomarker evidence alongside clinical symptoms to improve diagnostic accuracy and inform staging.[32] This approach enables early detection and personalized care planning, though challenges remain in standardizing biomarker use across clinical settings.

Routine neuroimaging, particularly magnetic resonance imaging, can help rule out certain causes of memory loss, such as vascular dementia, normal pressure hydrocephalus, chronic subdural hematomas, and brain tumors. Occasionally, such conditions are identified even in the absence of other clinical indicators. Neuroimaging should therefore be considered in all cases of progressive cognitive deterioration. Tests of potential metabolic abnormalities (e.g., hypothyroidism, vitamin B12 deficiency, electrolyte abnormalities) and infection (e.g., neurosyphilis) should be included in the workup. Occasionally, lumbar puncture may be needed, particularly in atypical cases (such as those associated with somnolence or confusion at the outset) or those with rapid progression. Electroencephalography, which is usually normal early in AD, may provide useful clues to alternative diagnosis in unusual cases.

Severe sleep disorders, disorders of liver and kidney function, and side effects of various medications can also produce cognitive dysfunction, as can depression (pseudodementia). Neuropsychiatric testing may be useful, then, to aid in the diagnosis of AD or to evaluate its progression. Such testing may be particularly helpful if the presentation is atypical.

Prevention and Treatment

Nutritional factors are paramount and are described in the Nutritional Considerations section below.

People who exercise, participate in intellectually stimulating activities, and remain active in social networks appear to be at lower risk for AD, and those affected may slow its progression through these activities.[33] Occupational therapy has been shown to improve daily functioning for patients with AD and to reduce caregiver strain.[34] Exercise programs can slow physical and functional decline.[35] Optimizing sleep allows the body to clear out degradative products of neural activity that accumulate during awake hours, such as beta-amyloid and tau proteins, that lead to plaques and tangles in the brain.[36]

Antivirals. As discussed above, use of common antiviral medications are associated with a significant reduction in AD risk.

Vaccines used for common infectious diseases have been shown to significantly reduce AD risk or delay its onset. This as been demonstrated for influenza vaccines,[37] as well as for combination vaccines used to reduce the risk of tetanus, diphtheria, and pertussis, and for pneumococcus and Herpes zoster (shingles).[38][39][40][41][42][43][44][45] The mechanism for this beneficial effect may be reduced risk of the target virus or bacterium, improved immune defenses in general, and/or an immune-boosting effect of adjuvant ingredients used in some vaccines.[46]

Lithium. As noted above, some studies suggest that lithium adequacy may reduce AD risk. Studies have shown benefits of low-dose lithium for mild cognitive impairment[47][48] and for AD.[49]

Drugs used for treating AD may have a modest effect.

• Memantine, an N-methyl-D-aspartate receptor antagonist along with galantamine, may slow the loss of mental and physical function. Memantine has modest effects in patients with moderate-to-advanced disease.[50]
• The benefits of cholinesterase inhibitors, such as donepezil, are modest, especially in advanced cases.[51]
• Aducanumab is a monoclonal antibody that reduces beta-amyloid plaque. Its use is associated with modest clinical benefits, frequent adverse effects (risk of brain swelling and/or bleeding), high cost, and challenges in administration.
• Lecanemab is approved for the treatment of early AD.[52]

Nutritional Considerations

Epidemiological and clinical studies have examined associations between diet and the risk of AD and cognitive decline.[53][54] The following factors are under study for a possible role in reducing risk:

Fruits and Vegetables

High intake of fruits and vegetables is associated with reduced risk of dementia, including AD. This has been particularly true for intake of berries, both for prevention and for cognitive improvement for those with memory deficits,[55][56][57][58][59][60] carotenoid-rich foods,[61][62] and cruciferous vegetables.[63]

Cardiovascular Risk Factors

Elevations in cardiovascular risk factors during the midlife period, including hypercholesterolemia, hypertension, obesity, and diabetes, are closely linked with AD and AD progression, suggesting the possibility that nutritional measures to alter these risk factors may reduce AD risk.[64][65][66]

Reduced Saturated Fat, Cholesterol, and Trans Fats

Ecological data have shown that the availability of animal products is more highly correlated with AD than any other types of foods.[67] The prospective Chicago Health and Aging Project reported that persons consuming the most saturated fat (compared with the least) had more than twice the risk of developing AD, compared with people consuming less saturated fat, and reported similar findings for trans fats.[68] Saturated fat is found primarily in dairy products, meat, and tropical oils (coconut, palm, and palm kernel oil). Trans fats are found in some snack foods and in dairy products and meats. Other studies have also implicated saturated fats in the cognitive decline that precedes AD.[69]

The mechanism may relate to the influence of dietary fat on blood cholesterol concentrations. Midlife hypercholesterolemia is associated with risk for AD. In addition, animal products are chief dietary sources of advanced glycation end products that are now thought to play a key role in the pathogenesis of AD.[70][71]

In contrast, higher intakes of unsaturated fats and a higher ratio of unsaturated to saturated fat are associated with a significantly lower risk for either cognitive decline or AD.[72] A meta-analysis of fish and omega-3 fatty acid intake found that higher compared with lower intake of fish was associated with a 36% lower risk of AD.[73]

Dietary patterns

Dietary patterns have been investigated for their influence on AD.

Mediterranean Diet. Observational studies have suggested that a Mediterranean diet reduces AD risk.[74][75][76] The term was coined by Ancel Keys for the dietary pattern in post-World-War II Italy favoring vegetables, fruits, and legumes with modest portions of animal products, and favoring olive oil over animal-based fats. However, a randomized trial did not support this benefit. In a 3-year trial combining a Mediterranean-style (“MIND” diet) with a caloric limit, brain scans showed about the same amount of hippocampal shrinkage and cognitive changes as in the control group.[77]

Vegan Diet and Other Interventions. A combination of a vegan diet and other interventions was tested by Dr. Dean Ornish at the Preventive Medicine Research Institute in a randomized trial for individuals with the initial signs of dementia consistent with early AD.[78] The program included a plant-based diet, mild exercise, stress management, and group support, along with several supplements: omega-fatty acids, a multivitamin-mineral supplement, coenzyme Q10, vitamin C, vitamin B12, magnesium L-threonate, lion’s mane extract, and a probiotic. By 20 weeks, 71 percent of intervention group participants stabilized or improved, while 29% declined. In the control group, 32% stayed the same, and 68% showed continued decline.

Consuming Vitamin E-Rich Foods

Vitamin E is a group of 8 antioxidant compounds. A meta-analysis found a significant association between vitamin E and reduced risk of developing AD. This effect was seen in studies examining diet alone (22% risk reduction) and supplements alone (17% reduction).[79] It should be noted that, unlike foods, vitamin supplements may contain only 1 of the 8 forms of vitamin E.

Clinical trials testing α-tocopherol supplementation as a treatment for mild to moderate AD cases have yielded mixed results.[80]

Increased Vitamin C

Studies have found that blood levels of vitamin C were lower in patients with both mild cognitive impairment and AD when compared with controls. In addition, individuals with higher vitamin C intakes (through diet and low-level supplementation of 500 mg/day or less) may have slower rates of cognitive decline than those with low intakes.[81]

In AD patients, no benefit was found in a 16-week study of a combination of vitamin C and E, lipoic acid, and Coenzyme Q10.[82] In contrast, a study in which AD patients were given a combination of an antioxidant (lipoic acid) and an omega-3 supplement over 12 months resulted in less decline in the Mini-Mental State Examination (MMSE) and Instrumental Activities of Daily Living (IADL).[83]

Micronutrient Adequacy

A systematic review and meta-analysis found that AD patients had significantly lower blood levels of vitamins A, B12, C, E, and folate, and nonsignificantly lower levels of vitamin D and zinc when compared with individuals without AD. Similar results were found even in AD patients who were not considered malnourished.[84] Given the large number of nutrients AD patients are lacking, a multiple vitamin supplement may be of benefit, provided it omits iron and copper, as noted below. Studies have found that multivitamin supplementation can improve cognition and memory.[85][86]

Lithium Adequacy

Lithium is found in green vegetables, legumes, cereals, nuts, mineral water, and in nutmeg, coriander, and cumin, although amounts vary depending on local conditions. Meat and dairy products are low in lithium.[87] Lithium levels are diminished by sodium and caffeine, both of which cause renal losses.

Avoiding Excess Copper

A meta-analysis examining copper levels in serum, plasma, and cerebrospinal fluid concluded that AD patients have a higher body copper burden than do normal individuals.[88] In addition, a higher-than-normal amount of this copper is unbound from its carrier (ceruloplasmin) in these patients, as a result of copper dysregulation seen in AD patients.[89] The consequence, apparently, is an increase in unbound copper in the brain.[90] This is of concern because brain copper increases with age and upregulates the expression of the amyloid beta precursor protein, increasing its aggregation and neurotoxicity.[91]

Avoiding Excess Iron

Some evidence suggests that excess iron may contribute to AD risk. Patients with AD have elevated iron levels in several brain areas affected by this disease, and an excess of iron in the brain is associated with beta-amyloid plaque formation, oxidative stress, synaptic dysfunction, and neuronal cell death.[92]

Iron transport through the blood-brain barrier is usually tightly controlled.[93] However, a damaged blood-brain barrier has been implicated in the development of AD and may precede the development of clinical symptoms. A Western diet has been linked to a compromised blood-brain barrier, thereby providing a possible mechanism by which iron could accumulate in the brain.[94] In the AD Neuroimaging Initiative cohort study, ferritin levels predicted the conversion from mild cognitive impairment to AD. Ferritin levels were also strongly associated with cerebrospinal fluid levels of apolipoprotein E and were elevated by the APOE-ɛ4allele, revealing that elevated brain iron adversely impacts disease progression.[95]

The higher absorbability of heme iron (found in animal products) may contribute to iron overload, in contrast to nonheme (from plant foods). Also, copper and iron are often added to multiple vitamin-mineral supplements. Patients should be encouraged to avoid such products unless iron or copper supplementation is specifically required.

Adequate Vitamin D Status

Vitamin D deficiency is associated with global cognitive impairment in adults, and a meta-analysis found the risk to be more than 20% greater for AD and dementia in persons whose vitamin D blood levels were in the deficient range (< 50 nmol/L) compared with individuals above this level.[96][97] Some studies suggest the risk could be even higher.[98] In addition, patients with AD are significantly more likely to have vitamin D deficiency than normal individuals,[99] though supplementation may accelerate plaque formation and exacerbate the disease.[100]

Avoiding Aluminum

Aluminum exposures can be neurotoxic, and some studies have shown associations between aluminum in drinking water and AD risk.[101] Unlike iron and copper, there is no requirement for aluminum in human biology.

Moderate Alcohol Consumption

Previous studies have found lower risk for dementia in light to moderate alcohol consumers compared with nondrinkers.[102][103] However, more recent studies have challenged these findings and indicate that even light drinking may increase AD risk.[104][105] In light of known hazards of light alcohol consumption, patients should not be advised to drink alcohol for AD prevention.[106]

Coffee

There is currently no consensus among studies regarding coffee’s effect on dementia risk. One meta-analysis found that drinking 1-4 cups of coffee per day was associated with a significantly lower risk of AD, while another found no significant protective effect.[107][108] Other studies have suggested a protective effect.[109][110]

Some have suggested that excessive coffee consumption (> 4 cups per day) may increase risk.[107] A large prospective study in 2021, including 398,646 UK Biobank participants aged 37-73 years, showed that abundant daily coffee consumption was associated with a significant loss of gray matter and increased risk of dementia.[111]

Orders

Orders

See Basic Diet Orders chapter.

Physical and occupational therapy consultation for home safety evaluation and needs assessment.

What to Tell the Family

A plant-based diet low in saturated fat, trans fats, and cholesterol, moderate in iron and copper, and high in dietary fiber and vitamins E and C may reduce the risk of AD, in addition to helping prevent other age-related debilitating diseases.

Safety precautions for AD patients are important. Connection with social services or a support group may also help ease the burden of care for a person with AD. Although routine genetic testing is not typically recommended, family members may want to be tested for the presence of the APOE4 allele. At minimum, they should be encouraged to mitigate their future risk of AD by noting the above recommendations.

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Last updated: June 10, 2026