Table 2.
Some systemic diseases that may lead to progressive cognitive impairment and dementia
| System | Examples | Associated symptoms | Diagnostic tests |
|---|---|---|---|
| CNS vascular disease | Primary and secondary CNS vasculitis | Headaches, focal neurological deficits | MRI; cerebral angiography; CSF analysis; brain biopsy; connective tissue disease screen (for example, ANA, C3/C4, RF, c-ANCA and p-ANCA, ENA-4 screen, cryoglobulins) |
| Infection | HIV-associated neurocognitive disorders Neurosyphilis Whipple's disease | Variable, constitutional symptoms, with or without opportunistic infections Tabes dorsalis Gastrointestinal symptoms, weight loss, and polyarthralgia; oculomasticatory and oculofacial-skeletal myorhythmia in only 20%, but highly specific | HIV screen; plasma HIV viral load; CD4 counts Serum RPR; MHA-TP; CSF VDRL Duodenal biopsy showing granular foamy macrophages with PAS-positive inclusions; CSF PCR for Tropheryma whipplei |
| Neoplastic | Primary CNS lymphoma | Headaches; focal neurological deficits | CSF analysis; brain/meningeal biopsy |
| Autoimmune/paraneoplastic | Hashimoto encephalitis | Thyroid abnormalities | Anti-microsomal antibody; anti-thyroglobulin antibody |
| Limbic encephalitis | Cancer (breast, lung, testicular, teratoma colon, gynecological) | Anti-Hu, anti-Ri, anti-Yo, anti-Ma1, anti-Ma2, anti-VGKC, anti-CV2, anti-amphiphysin, anti-NMDAR, anti-AMPAR, anti-GAD antibodies | |
| Lupus with CNS involvement | Multiple organ systems | ANA; ENA; CSF analysis; MRI | |
| Endocrine and nutritional | Hypothyroidism | Fatigue, weight gain, skin and hair changes, depression | TSH; free T4 |
| B12 Deficiency | Fatigue, macrocytic anemia, 'beefsteak' tongue, subacute combined degeneration of spinal cord | B12 |
AMPAR, 2-amino-3-(3-hydroxy-5-methyl-isoxazol-4-yl)propanoic acid receptors; ANA, antinuclear antibodies; ANCA, anti-neutrophil cytoplasmic antibodies; CNS, central nervous system; CSF, cerebrospinal fluid; ENA, extractable nuclear antigens; MHA-TP, microhemagglutination assay; MRI, magnetic resonance imaging; NMDAR, N-methyl-D-aspartate receptors; PAS, periodic acid-Schiff; RF, rheumatoid factor; RPR, Rapid Plasma Reagin; TSH, thyroid stimulating hormone; VDRL, Venereal Disease Research Laboratory test.