Modifiable, Non-Modifiable, and Clinical Factors Associated with Progression of Alzheimer's Disease

J Alzheimers Dis. 2021;80(1):1-27. doi: 10.3233/JAD-201182.


There is an extensive literature relating to factors associated with the development of Alzheimer's disease (AD), but less is known about factors which may contribute to its progression. This review examined the literature with regard to 15 factors which were suggested by PubMed search to be positively associated with the cognitive and/or neuropathological progression of AD. The factors were grouped as potentially modifiable (vascular risk factors, comorbidities, malnutrition, educational level, inflammation, and oxidative stress), non-modifiable (age at clinical onset, family history of dementia, gender, Apolipoprotein E ɛ4, genetic variants, and altered gene regulation), and clinical (baseline cognitive level, neuropsychiatric symptoms, and extrapyramidal signs). Although conflicting results were found for the majority of factors, a positive association was found in nearly all studies which investigated the relationship of six factors to AD progression: malnutrition, genetic variants, altered gene regulation, baseline cognitive level, neuropsychiatric symptoms, and extrapyramidal signs. Whether these or other factors which have been suggested to be associated with AD progression actually influence the rate of decline of AD patients is unclear. Therapeutic approaches which include addressing of modifiable factors associated with AD progression should be considered.

Keywords: Alzheimer’s disease; baseline cognition; extrapyramidal signs; genetic factors; malnutrition; neuropsychiatric symptoms; progression.

Publication types

  • Research Support, Non-U.S. Gov't
  • Review

MeSH terms

  • Adult
  • Aged
  • Aged, 80 and over
  • Alzheimer Disease / physiopathology
  • Alzheimer Disease / prevention & control*
  • Disease Progression
  • Humans
  • Middle Aged
  • Risk Factors