Background: Some levothyroxine (LT4)-treated hypothyroid patients report a constellation of persistent and distressing cognitive symptoms that has been termed brain fog. This narrative review focuses on attempts to define and measure hypothyroid-associated brain fog, summarize possible etiologies and contributing factors, present treatment options, and propose avenues for future research. Methods: Published literature was reviewed to summarize available information on patient-reported symptoms associated with brain fog in hypothyroidism, as well as objective evidence of impairment based on neurocognitive testing and functional imaging studies. Given the limited information specific for hypothyroid-associated brain fog, relevant data from other medical conditions associated with brain fog were also reviewed and incorporated into recommendations for clinical care and future research areas. Results: Hypothyroid-associated brain fog has not been well defined or quantitated, and the underlying pathophysiology is unclear. Symptoms vary among patients but commonly include fatigue, depressed mood, and cognitive difficulties in the areas of memory and executive function. Symptoms often predate the diagnosis of hypothyroidism, and the magnitude of cognitive impairment can range from mild to severe. Regardless of severity, these symptoms are associated with impaired quality of life and cause dissatisfaction with treatment, so often lead to requests for alternate therapies. Disease-specific and psychological factors impact the experience of brain fog in complex ways, including potential limitations in LT4 monotherapy, self-knowledge of a disease state, and expectations for therapeutic effects. Conclusions: Brain fog is a variable symptom complex in people with hypothyroidism, causing significant distress and diminished quality of life. In the absence of proven therapies, individualized treatment plans are recommended, which incorporate thyroid-specific, general medical, and psychosocial approaches. In particular, cognitive rehabilitation is an underutilized technique that is beneficial in other medical conditions associated with brain fog and could improve symptoms in hypothyroid people. The limitations in our current knowledge and questions presented throughout this review highlight a major need for clinical research in this understudied area. Future research should include attention to standardization of survey instruments to quantitate brain fog in hypothyroid people, as well as rigorously designed intervention studies.
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