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diagnostic criteria for Alzheimer's disease

Diagnostic criteria: clinical diagnosis 1) development of multiple cognitive deficits a) memory impairment must be present - recent (secondary) memory generally occurs early (inability to learn new information) b) one or more of the following cognitive disturbances 1] aphasia 2] apraxia 3] agnosia 4] disturbance in executive function 2) significant impairment on social or occupational functioning representing a significant decline from a previous level of functioning 3) gradual onset & progressive cognitive decline 4) cognitive deficits are not due to a) other central nervous system conditions that cause progressive deficits in memory & cognition b) systemic conditions known to cause dementia c) substance-induced conditions 5) deficits do not occur exclusively during episodes of delirium 6) disturbance is NOT better accounted for by another axis I disorder (i.e. schizophrenia) 7) CERAD [6] ATN classification system based on biomarkers (research)* [5] - beta-amyloid deposition - neurofibrillary tau - paired helical filaments - neurofibrillary tangles - neurodegeneration [5] Alzheimer's Association Workgroup [7] - AD is a biological process that begins with the appearance of AD neuropathologic changes (neuritic plaques & neurofibrillaty tangles) while people are asymptomatic - progression of the neuropathologic burden leads to the later appearance & progression of clinical symptoms - early-changing Core 1 biomarkers (amyloid PET), approved CSF biomarkers, & plasma biomarkers (plasma ptau-217) map onto the AD neuropathologic changes - an abnormal Core 1 biomarker result is sufficient to establish a diagnosis of AD & to inform clinical decision making throughout the disease continuum - later-changing Core 2 biomarkers (biofluid, tau PET) can provide prognostic information, & if abnormal, increase confidence that symptoms are due to AD [7] Staging: Alzheimer's Association Workgroup [7] - an integrated biological & clinical staging scheme that accommodates the fact that common copathologies, cognitive reserve, & resistance may modify relationships between clinical & biological AD stages [7] Braak staging [5]: A4 deposition & neurofibrillary tangles - distribution of amyloid plaques varies widely - stage A: basal neocortical areas - stage B: superiolateral spread - stage C: extension into primary neocortical areas - six stages distinguished by location and severity of changes - trans-entorhinal stages I-II: clinically silent - involvement confined - limbic stages III-IV: incipient AD - involvement of CA1 - neocortical stages V-VI: fully developed AD - involvement of all areas of association cortex * biomarkers from imaging & biofluids [5] * although it is possible that beta-amyloid plaques & neurofibrillary tangles are not causal in Alzheimer's disease (AD) pathogenesis, it is these abnormal deposits that define AD as a unique neurodegenerative disease among different disorders that can result in dementia [5]

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criteria for Alzheimer's disease

References

  1. Role of cholinergic therapy in treatment of Alzheimer's disease & other dementias, Farlow, M et al, 2001
  2. DSM IV
  3. Jack CR Jr, Albert MS, Knopman DS et al Introduction to the recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011 May;7(3):257-62. PMID: 21514247
  4. McKhann GM, Knopman DS, Chertkow H et al The diagnosis of dementia due to 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):263-9. PMID: 21514250
  5. Jack CR Jr, Bennett DA, Blennow K et al NIA-AA Research Framework: Toward a biological definition of Alzheimer's disease. Alzheimers & Dementia. April 2018, 14(4):535-562 PMID: 29653606 http://www.alzheimersanddementia.com/article/S1552-5260(18)30072-4/fulltext - Jack CR Jr, Bennett DA, Blennow K et al A/T/N: An unbiased descriptive classification scheme for Alzheimer disease biomarkers. Neurology. 2016 Aug 2;87(5):539-47. Epub 2016 Jul 1. Review. PMID: 27371494 Free PMC Article
  6. Mirra et al. The consortium to establish a registry for Alzheimer's disease (CERAD). Part II. Standardization of the neuropathologic assessment of Alzheimer's disease. Neurology 41:479-486, 1991 PMID: 2011243 - Gearing et al. The Consortium to Establish a Registry for Alzheimer's Disease (CERAD). Part X. Neuropathology confirmation of the clinical diagnosis of Alzheimer's disease. Neurology 45:461-6 1995. PMID: 7898697 - http://www.alzforum.org/dis/dia/cli/Consensus.asp - http://www-cfas.medschl.cam.ac.uk/neuro_forms.htm
  7. Jack CR Jr, Andrews JS, Beach TG et al Revised criteria for diagnosis and staging of Alzheimer's disease: Alzheimer's Association Workgroup. Alzheimers Dement. 2024 Jun 27. PMID: 38934362 https://alz-journals.onlinelibrary.wiley.com/doi/10.1002/alz.13859