The neuropsychological mechanism underlying cognitive impairment in hypothyroidism is poorly understood. It is not known whether cognitive impairment resolves following L-Thyroxine (LT4) replacement. It is also unknown whether similar neuropsychological abnormalities occur in patients with sub-clinical hypothyroidism (SCH). To address these questions, we performed neuropsychological tests in 17 patients with hypothyroidism (age 45±3 years; mean±S.E.M.), 17 patients with SCH (age 49±2), before and following LT4 replacement for 3 months and 12 matched control subjects (age 41±2).
Subjects were assessed for anxiety and depression (Hospital Anxiety and Depression Scale); IQ (National Adult Reading Scale); working (n-Back Working Memory task), spatial (Rey Osterrieth Fig.), verbal (Rivermead Short Stories) and associative (Face-Name Learning) memory. ANOVA with post-hoc testing was used for analysis.
Before treatment, both SCH and hypothyroid patients were more anxious and depressed, and performed worse on tests of visual and verbal memory compared to normal subjects (P<0.05). Significant (P<0.05) impairments of associative and working memory were observed in the hypothyroid group. Following 3 months of LT4 replacement, SCH and hypothyroid patients were less anxious and depressed (P<0.05) and displayed improvements (P<0.05) in spatial, verbal and associative memory, although these scores remained impaired (P<0.05) compared to normal subjects. Interestingly, while the hypothyroid patients had significantly lower IQ scores at both time points, their scores improved following 3 months treatment (P<0.05).
In summary, neuropsychological deficits occur in overt and sub-clinical hypothyroidism. Short-term LT4 replacement improves but does not normalise anxiety, depression, spatial, verbal and associative memory. It does nott improve working memory. These data provide preliminary evidence that LT4 replacement is important in SCH. Further studies are needed to clarify this, and to determine whether long-term LT4 replacement normalises these deficits in SCH and overt hypothyroidism.