| Age at symptom onset less than 65 years. |
Symptoms often begin in the 50s or late 40s. |
| ApoE ε4-negative genotype. |
Typically ApoE3/3 unless there are other risk factors. |
| Negative family history or family history positive with symptom onset only in much older individuals than the patient. |
|
| Symptom onset in association with menopause or andropause. |
|
| Depression as a preceding or significant accompaniment of the cognitive decline. |
|
| Headache as an early or preceding symptom. |
|
| Atypical presentation, in which memory consolidation is not the initial and dominant characteristic. |
Typical deficits include executive deficits, dyscalculia, paraphasias, or aphasia. |
| Precipitation or exacerbation by a period of great stress (e.g., loss of employment or marriage dissolution or family change) and sleep loss. |
The degree of dysfunction is also markedly affected by stress and sleep loss. |
| Exposure to mycotoxins or metals (e.g., inorganic mercury via amalgams, or organic mercury via the consumption of large fish such as tuna) or both. |
|
| Diagnosis of CIRS with cognitive decline. |
Cognitive decline is common with CIRS. |
| Imaging suggestive of more than typical Alzheimer's involvement. |
FDG-PET may show frontal as well as temporoparietal reductions in glucose utilization, even early in the course of the illness; MRI may show generalized cerebral and cerebellar atrophy, especially with mild FLAIR (fluid-attenuated inversion recovery) hyperintensity. |
| Low serum triglycerides or triglyceride:total cholesterol ratio. |
Triglycerides are often in the 50s. |
| Low serum zinc (<75mcg/dl) or RBC zinc, or high copper:zinc ratio (>1.3). |
|
| HPA axis dysfunction, with low pregnenolone, DHEA-S, and/or AM cortisol. |
|
| High serum C4a, TGF-β1, or MMP9; or low serum MSH (melanocyte-stimulating hormone). Positive deep naso-pharyngeal culture for MARCoNS. |
See reference 5. |
| HLA-DR/DQ associated with multiple biotoxin sensitivities or pathogen-specific sensitivity. |
See reference 5. |
