Objective:

To highlight diagnostic challenges at the intersection of neurodegenerative and inflammatory neurologic disease in early-onset cognitive decline with incidentally identified systemic sarcoidosis.

Background:

Cognitive decline with focal neurologic deficits raises concern for inflammatory, autoimmune, or neurodegenerative etiologies. Sarcoidosis disproportionately affects Black patients and may involve the nervous system. Interpretation of Alzheimer’s disease (AD) biomarkers and genetic risk factors, including APOE ε4, may vary across populations, complicating diagnostic evaluation.

Design/Methods:

We describe a 58-year-old Black woman with progressive cognitive decline beginning before age 60, followed by acute unilateral ptosis. Chest imaging revealed incidental pulmonary abnormalities, with biopsy confirming sarcoidosis. MRI brain with contrast showed no leptomeningeal or cranial nerve enhancement, with diffuse temporal and frontal atrophy. Cerebrospinal fluid demonstrated an AD-consistent biomarker profile (elevated phosphorylated tau, reduced amyloid beta) without pleocytosis or other clear evidence of central nervous system inflammation. Neuropsychological testing demonstrated severe multidomain impairment, including episodic memory, executive dysfunction, language, and visuospatial deficits. Genetic testing revealed APOE ε4 homozygosity. The cranial neuropathy resolved spontaneously.

Results:

Despite systemic sarcoidosis, cranial neuropathy, and cognitive decline prompting multidisciplinary consideration of neurosarcoidosis, there was no objective evidence of central nervous system inflammation. Converging biomarker, imaging, genetic, and neuropsychological findings supported early-onset AD. Neurosarcoidosis was considered; however, corticosteroid therapy was deferred, given the absence of inflammatory markers and potential risk without clear benefit.

Conclusions:

Incidentally identified inflammatory disease may introduce diagnostic ambiguity in cognitive decline. Careful integration of clinical, radiographic, and biomarker data is essential to avoid both premature diagnostic closure and unnecessary immunosuppression in atypical presentations.