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Alzheimer’s disease (AD)

AD is a neurodegenerative disease. In a person with AD, cognitive decline and functional impairment are much more severe than can be explained by just the person’s age.

Our evidence-based analysis on alzheimer’s disease (ad) features 18 unique references to scientific papers.

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Summary of Alzheimer’s disease (AD)

Alzheimer’s disease (AD) is currently the fifth leading cause of death for people older than 65 in the United States.[1] Its exact underlying cause is far from a settled subject, but the features shared by the brains of people with AD may provide insights.

One of the main histopathological features of AD is the accumulation of amyloid plaques in the brain.[2] These plaques, which are made up of a peptide called amyloid beta, have been proposed as a major driver of AD. This “amyloid hypothesis” has been challenged, however,[3] notably because drugs targeting the amyloid pathway have not been found to improve cognition in AD.[4] But maybe the drug trials were started too late in the course of the disease.[5]

The amyloid hypothesis of Alzheimer’s disease

Sources: Alves et al. J Alzheimers Dis. 2021 Jun[6] ♦ Saxena. Expert Opin Ther Targets. 2010 Dec[7]

Another primary histopathological feature of AD is the presence of neurofibrillary tangles in the brain.[8] These tangles are made up of tau proteins that, like amyloid beta, have misfolded and aggregated. According to the “tau hypothesis”, these tangles are a cause or contributor to AD. However, because tau proteins normally serve important functions in the brain, another possibility is that tau tangles are simply an indicator of a loss of tau function and are not themselves harmful.

Also common in AD is hypometabolism,[9] a reduction in the brain’s ability to metabolize glucose for energy — which is why some researchers call AD “type 3 diabetes”.[10] This reduction in the brain’s energy production may contribute to the cognitive impairments seen with AD and might contribute to the development of the disease itself.[11][12][13]

Finally, AD is a neurodegenerative disease: it is characterized by neuronal death and subsequent cerebral atrophy.[14] This process is widely believed to be central to the disease process and may be the result, at least in part, of some or all the previously mentioned factors.

Neurological features of Alzheimer’s disease

No drugs have been shown to slow or prevent AD: nearly all of the existing drugs approved to treat AD (e.g., acetylcholinesterase inhibitors) merely improve symptoms, and these improvements are often fairly minor. Therefore, nonpharmaceutical strategies to prevent AD need to be explored.

One such strategy may be a Mediterranean diet, an eating pattern typically characterized by higher intakes of fish, fruit, vegetables, legumes, nuts, whole grains, and olive oil; a limited intake of meat and dairy; and a moderate intake of alcohol (often wine specifically). A 2021 systematic review and meta-analysis summarized here found observational evidence that adherence to a Mediterranean diet was associated with lower risks of both mild cognitive impairment and AD.[15] (A “mild cognitive impairement” is a neurocognitive disorder involving memory problems that exceed what is expected based on a person’s age. It is often a precursor to AD.)

Another, compatible dietary strategy is to avoid consuming too much sugar, since a 1-year prospective cohort study summarized here found that a diet with a high glycemic index was associated with more amyloid-beta peptide accumulation in the precuneus, a pathological hallmark of Alzheimer’s disease. This association was stronger in participants with elevated amyloid at baseline.[16]

Alzheimer's disease is the most common form of dementia. Some of the other common types of dementia are Lewy Body dementia, Parkinson’s disease dementia, vascular dementia, and frontotemporal dementia. In general, these all vary somewhat in their presentation.

Common types of dementia
Type of dementiaUnderlying pathologyPercentage of all dementias (estimated)Suggestive characteristics
Alzheimer’s disease
Amyloid plaques and neurofibrillary tangles in the brain
  • Gradual onset

  • Progressive course

  • Multiple cognitive deficits including memory impairment

Vascular dementia
Marker of CVD event (infarcts, occlusion of arteries)
  • Abrupt onset

  • Course fluctuates

  • History of CVD event

  • Focal deficits (abnormal gait, muscle weakness, etc.)

Lewy body dementia
Alpha-synuclein aggregates in the brain
  • Fluctuations in cognition

  • Hallucinations

  • Difficulty walking

Frontotemporal dementia
Degeneration of frontal and temporal lobes
3% (people >65 years old) and 10% (people <65 years old)
  • Impulsivity

  • Difficulty with language (aphasia)

  • Executive dysfunction

  • Visuospatial function usually unaffected

*Adapted from Duong et al. Can Pharm J (Ott). 2017 Feb[17] and Hogan et al. Can J Neurol Sci. 2016 Apr[18]

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