The National Institute on Aging and the Alzheimer’s Association (NIA-AA) charged a workgroup with the task of developing criteria for the symptomatic predementia phase of Alzheimer’s disease (AD), referred to in this article as mild cognitive impairment due to AD.
Probable AD dementia is a syndrome of dementia defined by the following characteristics:
- Interference with ability to function at work or at usual activities
- A decline from a previous level of functioning and performing
- Not explained by delirium or major psychiatric disorder
- Cognitive impairment established by history-taking from the patient and a knowledgeable informant; and objective bedside mental status examination or neuropsychologic testing
- Cognitive impairment involving a minimum of two of the following domains:
- Impaired ability to acquire and remember new information
- Impaired reasoning and handing of complex tasks, poor judgment
- Impaired visuospatial abilities
- Impaired language functions
- Changes in personality, behavior or comportment
Other core clinical criteria include:
- Insidious onset
- Clear-cut history of worsening
- Initial and most prominent cognitive deficits are one of the following:
- Amnestic presentation (ie, impairment in learning and recall of recently learned information)
- Nonamnestic presentations include either a language presentation, with prominent word-finding deficits; a visuospatial presentation, with visual cognitive deficits; or a dysexecutive presentation, with prominent impairment of reasoning, judgment and/or problem solving
- No evidence of substantial concomitant cerebrovascular disease, core features of dementia with Lewy bodies (DLB), prominent features of behavioral variant frontotemporal dementia or prominent features of semantic or nonfluent/agrammatic variants of primary progressive aphasia, or evidence of another concurrent, active neurologic or non-neurologic disease or use of medication that could have a substantial effect on cognition.
Possible AD includes either of the following clinical scenarios:
- Atypical course: The core clinical criteria above are met in terms of the nature of the cognitive deficits, but there is either a sudden onset of cognitive impairment or insufficient historical detail or objective documentation of progressive decline.
- Etiologically mixed presentation: All of the core clinical criteria for AD dementia are met but the individual also has evidence of concomitant cerebrovascular disease, features of DLB other than the dementia itself, or evidence for another neurologic or medical comorbidity or medication that could have a substantial effect on cognition.
Biomarkers under examination for AD
A- Biomarkers of Aβ deposition
- CSF Aβ42
- PET amyloid imaging
B- Biomarkers of neuronal injury
- CSF tau/phosphorylated-tau
- Hippocampal volume or medial temporal atrophy by volumetric measures or visual rating
- Rate of brain atrophy
- FDG-PET imaging
- SPECT perfusion imaging
- Less well validated biomarkers: fMRI activation studies, resting BOLD functional connectivity, MRI perfusion, MR spectroscopy, diffusion tensor imaging, voxel-based and multivariate measures
C- Associated biochemical change
- Inflammatory biomarkers (cytokines)
- Oxidative stress (isoprostanes)
- Other markers of synaptic damage and neurodegeneration such as cell death
Abbreviations: Aβ, beta-amyloid protein; CSF, cerebrospinal fluid; PET, positron emission tomography; FDG, fluorodeoxyglucose; SPECT, single photon emission tomography; MRI, magnetic resonance imaging; fMRI, functional magnetic resonance imaging; BOLD, blood oxygen level-dependent; MR, magnetic resonance.
- McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carrillo MC, Thies B, Weintraub S, Phelps CH. 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. [Medline]
- Morris JC. Revised criteria for mild cognitive impairment may compromise the diagnosis of Alzheimer disease dementia. Arch Neurol. 2012 Jun;69(6):700-8. [Medline]
Created: May 24, 2018.