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preclinical Alzheimer's disease

Terms created for research purposes. Etiology: - asymptomatic cerebral amyloidosis * genetic markers are not included Diagnostic criteria: NINCDS-ADRDA criteria: - asymptomatic Clinical manifestations: - missing bill payments & other financial mistakes [10] Laboratory: - CSF Abeta40/Abeta42 used to identify preclinical Alzheimer's disease [9] - plasma P-tau217 predicts cognitive decline in patients with preclinical AD [12] * also see laboratory investigation of Alzheimer's disease Special laboratory: - optical coherence tomography angiography [3] - evidence of retinal vascular & microvascular dysfunction - GPS* monitoring may identify driving features that predict preclinical Alzheimer's disease [9] - average jerk - excessive braking - number of night trips - radius of gyration, - number of trips shorter than 1 mile * GPS: global positioning system Radiology: - beta-amyloid identified by amyloid PET using [18F]-florbetapir - heterogeneous cortical tau PET patterns found inpatients with preclinical AD [11] * also see radiology of Alzheimer's disease Complications: - most persons with preclinical Alzheimer's disease will not develop dementia during their lifetime [4] - consequences of overdiagnosis [7] - cardiovascular risk synergistically combines with beta-amyloid burden in risk for cognitive decline & dementia [6] Management: - physical activity & vascular risk reduction may attenuate risks of associated with beta-amyloid on cognitive decline & neurodegeneration in asymptomatic persons [8]

Interactions

disease interactions

General

Alzheimer's disease (AD)

References

  1. Geriatric Review Syllabus, 8th edition (GRS8) Durso SC and Sullivan GN (eds) American Geriatrics Society, 2013
  2. Sperling RA, Aisen PS, Beckett LA et al Toward defining the preclinical stages of Alzheimer's disease: recommendations from the National Institute on Aging- Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):280-92. PMID: 21514248
  3. George J Eyes Might ID Preclinical Alzheimer's. Presymptomatic patients show foveal thinning, retinal changes. MedPage Today. April 24, 2018 https://www.medpagetoday.com/meetingcoverage/aan/72508 - Van Stavern G, et al Optical coherence tomography angiography in pre-clinical Alzheimer's disease. American Academy of Neurology (AAN) 2018.
  4. George J. Most Preclinical AD Doesn't Progress to Dementia. Model is the first to include biomarkers in lifetime Alzheimer's dementia risk. MedPage Today. May 22, 2018 https://www.medpagetoday.com/neurology/alzheimersdisease/73046 - Brookmeyer R, Abdalla N Estimation of lifetime risks of Alzheimer's disease dementia using biomarkers for preclinical disease. Alzheimer's & Dementia 2018; PMID: 29802030
  5. Brookmeyer R, Abdalla N, Kawas CH, Corrada MM. Forecasting the prevalence of preclinical and clinical Alzheimer's disease in the United States. Alzheimers Dement. 2018 Feb;14(2):121-129. PMID: 29233480
  6. Rabin JS, Schultz AP, Hedden T et al Interactive Associations of Vascular Risk and beta-Amyloid Burden With Cognitive Decline in Clinically Normal Elderly Individuals. Findings From the Harvard Aging Brain Study. JAMA Neurol. Published online May 21, 2018 PMID: 29799986 https://jamanetwork.com/journals/jamaneurology/fullarticle/2680896
  7. Langa KM, Burke JF. Preclinical Alzheimer Disease - Early Diagnosis or Overdiagnosis? JAMA Intern Med. Published online July 8, 2019 PMID: 31282928 Free PMC Article https://jamanetwork.com/journals/jamainternalmedicine/fullarticle/2737753
  8. Rabin JS, Klein H, Kirn DR et al Associations of Physical Activity and beta-Amyloid With Longitudinal Cognition and Neurodegeneration in Clinically Normal Older Adults. JAMA Neurol. Published online July 16, 2019. PMID: 31312836 https://jamanetwork.com/journals/jamaneurology/fullarticle/2738357
  9. George J Driving Patterns Pinpoint Early Alzheimer's Disease. Subtle shifts in on-road behavior suggest GPS-based biomarkers may have merit. MedPage Today July 30, 2021 https://www.medpagetoday.com/meetingcoverage/aaic/93840 - Bayat S, Babulal GM., Schindler SE et al. GPS driving: a digital biomarker for preclinical Alzheimer disease. Alz Res Therapy 2021 13, 115 https://alzres.biomedcentral.com/articles/10.1186/s13195-021-00852-1
  10. Nicholas LH, Langa KM, Bynum JP et al Financial Presentation of Alzheimer Disease and Related Dementias. JAMA Intern Med. 2021;181(2):220-227. PMID: 33252621 https://jamanetwork.com/journals/jamainternalmedicine/article-abstract/2773241
  11. Young CB, Winer JR, Younes K et al Divergent Cortical Tau Positron Emission Tomography Patterns Among Patients With Preclinical Alzheimer Disease. JAMA Neurol. Published online April 18, 2022 PMID: 35435938 https://jamanetwork.com/journals/jamaneurology/fullarticle/2790807
  12. George J Blood Test Predicts Which People With Amyloid Are Likely to Decline Cognitively. Plasma p-tau217 outperformed other preclinical Alzheimer's measures. MedPage Today February 6, 2023 https://www.medpagetoday.com/neurology/alzheimersdisease/102970 - Mattsson-Carlgren N, Salvado G, Ashton NJ et al Prediction of Longitudinal Cognitive Decline in Preclinical Alzheimer Disease Using Plasma Biomarkers. JAMA Neurol. Published online February 6, 2023 PMID: 36745413 https://jamanetwork.com/journals/jamaneurology/fullarticle/2801289