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predictors of Alzheimer's disease

Etiology: 1) 5 strong predictors of developing Alzheimer's disease (AD) in patients with mild cognitive impairment (MCI) include: [1] a) hippocampus volume on MRI b) entorhinal cortex volume on MRI c) selective reminding test of immediate recall d) functional activities questionnaire e) Pennsylvania Smell Identification Scale (UPSIT) 2) memory impairment predominant (amnestic) mild cognitive impairment often precedes Alzheimer's disease [8] - difficulty remembering events - difficulty remembering recent conversations [16] 3) disruption of circadian rhythms occur prior to the emergence of cognitive impairment [2] 4) non-REM sleep slow wave activity is inversely related to Alzheimer's pathology, especially tauopathy [3] - association most evident at lowest (1-2 Hz) frequencies 5) CSF IL-9 is a predictor in African Americans but not Caucasians [4] 6) increased risk of dementia associated with tooth loss [11] 7) HDL cholesterol & serum triglycerides linked with AD [13] - risk of AD diminished by 15% in adults age 35-50 years & by 18% in adults age 51-60 years for every 15 mg/dL increase in HDL cholesterol [13] - serum triglycerides levels were associated with risk of AD only in adults 35-50 years [13] 8) 15 mg/dL increase in blood glucose in adults age 51-60 years is associated with a 14% increased risk of AD [13] Clinical manifestations: - linguistic dysfunction predicts AD before age 85 years [6] - difficulty managing money may be an early sign of cognitive impairment in the elderly [7] - older adults who subsequently develop Alzheimer's disease - more likely to have had a fall in the previous 12 months than controls [15] Laboratory: - plasma phospho-tau combined with executive function & memory tests can predict Alzheimer's disease within 2-6 years among older persons with memory complaints [9] - higher plasma p-tau217 predicts brain atrophy & worse cognition in preclinical AD [10] - CSF p-tau181/amyloid-beta42 [14] - higher plasma Abeta40/42 predicts increased longitudinal amyloid-PET signals [10] - U-p53AZ in blood (AlzoSure Predict) allegedly & predict AD 6 years in advance [12] Special laboratory: - Fastball EEG: may identify early Alzheimer's disease from normal elderly - older adults who subsequently develop Alzheimer's disease - score worse than controls on fluid intelligence, reaction time, numeric memory, prospective memory, & pair-matching [15] Radiology: - amyloid PET imaging [14]

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Alzheimer's disease (AD) etiology/risk of Alzheimer's disease prevention of Alzheimer's disease/dementia

References

  1. Devanand DP et al, Combining early markers strongly predicts conversion from mild cognitive impairment to Alzheimer's disease. Biol Psychiatry 2008, 64:871 PMID: 18723162
  2. George J. Circadian Dysfunction May ID Preclinical Alzheimer's. Fragmented rhythms associated with plaque pathology. MedPage Today. January 29, 2018 https://www.medpagetoday.com/neurology/alzheimersdisease/70815 - Musiek E et al Circadian rest-activity pattern changes in aging and preclinical Alzheimer disease. JAMA Neurology 2018; - Musiek ES. Circadian Rhythms in AD pathogenesis: A Critical Appraisal. Curr Sleep Med Rep. 2017 Jun;3(2):85-92. PMID: 29308355 - Musiek ES, Holtzman DM. Mechanisms linking circadian clocks, sleep, and neurodegeneration. Science. 2016 Nov 25;354(6315):1004-1008. Review. PMID: 27885006 Free PMC Article
  3. George J Deep Sleep Linked to Early Alzheimer's Signs Non-REM slow wave activity tied to tau pathology. MedPage Today. Jan 10, 2019 https://www.medpagetoday.com/neurology/alzheimersdisease/77361
  4. Wharton W, Kollhoff AL, Gangishetti U et al. Interleukin 9 alterations linked to alzheimer disease in african americans. Ann Neurol 2019 Sep; 86:407. PMID: 31271450 https://onlinelibrary.wiley.com/doi/full/10.1002/ana.25543
  5. George J Long, Frequent Naps Predict Alzheimer's Dementia - Study uses actigraphy to assess snoozing, drowsiness in elderly adults/ MedPage Today August 29, 2020 https://www.medpagetoday.com/meetingcoverage/apss/88350 - Li P, et al Longer And More Frequent Naps Predict Incident Alzheimer's Dementia In Community-based Older Adults SLEEP 2020; Abstract 1135
  6. George J Language Predicts Alzheimer's Onset - AI model uses linguistic dysfunction to spot future dementia. MedPage Today October 26, 2020 https://www.medpagetoday.com/neurology/alzheimersdisease/89340 - Eyigoz E, Mathur S, Santamaria M, Cecchi G, Naylor M Linguistic markers predict onset of Alzheimer's disease. EClinicalMedicine 2020 Oct 22;28:100583 PMID: 33294808 Free PMC article. https://www.thelancet.com/journals/eclinm/article/PIIS2589-5370(20)30327-8/fulltext
  7. Andrews M Trouble Managing Money May Be an Early Sign of Dementia. Annals of Long-Term Care. May 5, 2021 https://www.managedhealthcareconnect.com/annals-long-term-care/trouble-managing-money-may-be-early-sign-dementia
  8. Lutsep HL Fast Five Quiz: Memory Loss and Cognitive Impairment Medscape. April 28, 2021 https://reference.medscape.com/viewarticle/949619
  9. Palmqvist S, Tideman P, Cullen N et al Prediction of future Alzheimer's disease dementia using plasma phospho-tau combined with other accessible measures. Nat Med 2021. May 24 PMID: 34031605 https://www.nature.com/articles/s41591-021-01348-z
  10. Pereira JB et al. Plasma markers predict changes in amyloid, tau, atrophy and cognition in non-demented subjects. Brain 2021 Jun 2; [e-pub]. PMID: 34077494 https://academic.oup.com/brain/advance-article/doi/10.1093/brain/awab163/6291241
  11. Qi X, Zhu Z, Plassman BL, Wu B Dose-Response Meta-Analysis on Tooth Loss With the Risk of Cognitive Impairment and Dementia. JAMDA 2021. July 8 PMID: 34579934 PMCID: PMC8479246 (available on 2022-10-01) https://www.jamda.com/article/S1525-8610(21)00473-4/fulltext
  12. Anderson P New Blood Test May Detect Preclinical Alzheimer's Years in Advance. Medscape. November 23, 2021 https://www.medscape.com/viewarticle/963509
  13. George J. Blood Profile at Age 35 Linked to Subsequent Alzheimer's Dementia. Associations extend much earlier in life than previously thought. MedPage Today March 24, 2022 https://www.medpagetoday.com/neurology/dementia/97854 - Zhang X, Tong T, Chang A et al Midlife lipid and glucose levels are associated with Alzheimer's disease. Alzheimer's & Dementia. 2022. March 22 PMID: 35319157 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12641
  14. Long JM et al. Preclinical Alzheimer's disease biomarkers accurately predict cognitive and neuropathological outcomes. Brain 2022 Jul 22; [e-pub]. PMID: 35867858 https://academic.oup.com/brain/advance-article-abstract/doi/10.1093/brain/awac250/6648721
  15. George J Dementia Signs Emerge Up to 9 Years Before Diagnoses. Cognitive, functional changes spotted in pre-Alzheimer's patients and others. MedPage Today October 15, 2022 https://www.medpagetoday.com/neurology/alzheimersdisease/101242 - Swaddiwudhipong N, Whiteside DJ, Hezemans FH et al Pre-diagnostic cognitive and functional impairment in multiple sporadic neurodegenerative diseases. Alzheimer's & Dmentia. 2022. Oct 12 https://alz-journals.onlinelibrary.wiley.com/doi/full/10.1002/alz.12802
  16. NEJM Knowledge+ Psychiatry