Evidence for a Specific Defect in Hippocampal Memory in Overt and Subclinical Hypothyroidism

Context: Declarative memory largely depends upon normal functioning temporal lobes (hippocampal complex) and prefrontal cortex. Animal studies suggest abnormal hippocampal function in hypothyroidism. Objective: The aim of the study was to assess declarative memory in overt and subclinical (SCH) hypothyroid patients before and after l-T4 (LT4) replacement and in matched normal subjects. Design and Setting: A prospective, open-labeled interventional study was conducted at a teaching hospital. Participants and Intervention: Hypothyroid (n = 21) and SCH (n = 17) patients underwent neuropsychological tests at baseline and 3 and 6 months after LT4 replacement. Normal subjects were studied at the same time-points. Main Outcome: Tests of spatial, verbal, associative, and working memory; attention; and response inhibition and the Hospital Anxiety and Depression Scale were administered. Results: Baseline deficits in spatial, associative, and verbal memory, which rely upon the integrity of the hippocampal and frontal areas, were identified in patients with overt hypothyroidism. Spatial and verbal memory were impaired in SCH patients (P < 0.05). TSH levels correlated negatively (P < 0.05) with these deficits. After LT4 replacement, verbal memory normalized. Spatial memory normalized in the SCH group but remained impaired in the hypothyroid group. Associative memory deficits persisted in the overt hypothyroid group. Hospital Anxiety and Depression Scale scores did not correlate with cognitive function. Measures of attention and response inhibition did not differ from control subjects. Conclusion: Cognitive impairment occurs in SCH and more markedly in overt hypothyroidism. These impairments appear predominantly mnemonic in nature, suggesting that the etiology is not indicative of general cognitive slowing. We propose that these deficits may reflect an underlying disruption of normal hippocampal function and/or connectivity. Memory deficits in subclinical and overt hypothyroidism are indicative of an underlying hippocampal deficit, although the exact underlying neuronal deficits will require further elucidation.