Revisiting Dementia’s Relationship to Hypothyroidism

Bushra Qureshi, MD; Mashal Khan, MD; Dharmendra Goyal, MD; Steven Lippmann, MD

Regulated by the pituitary gland and in part by the hypothalamus, the thyroid gland releases two hormones—thyroxine (T4) and triidotyronine (T3)—that exert profound effects on many physiological processes of development, growth, and metabolism. Moderate atrophy of the thyroid gland and other changes in thyroid hormone (TH) function and metabolism are common in normal aging,^1-3 however, if left untreated TH deficiency can cause complications such as hypertension, hyperlipidemia, myxedema coma, and cognitive deficits over time.⁴ The risk factors of hypothyroidism are age 50 years and older, female sex, obesity, thyroid surgery, and radiation exposure to the neck. The common and uncommon causes of hypothyroidism in elderly patients are outlined in Table 1.

Overt hypothyroidism in elderly individuals is a cause of dementia,⁵ and is prevalent in 2% to 5% of persons aged 65 years and older.⁴ Subclinical hypothyroidism, defined as isolated elevation of thyroid-stimulating hormone (TSH) levels with normal T4 and T3, with or without symptoms, is estimated to affect another 5% to 10% of people aged 65 years or older. Primary care providers should be aware of the increasingly high prevalence of hypothyroidism in older adults, as they can present with nonspecific symptoms such as fatigue, weakness, depression, constipation, and dry skin as well as confusion, anorexia, incontinence, and decreased mobility.⁴ This article highlights one important complication of TH deficiency in particular: dementia. The role of TH in cognitive health and the recognition and treatment of hypothyroidism in older patients to prevent hypothyroid-induced dementia is discussed.
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Thyroid Hormone in the Aging Brain

TH acts on the central nervous system as a neuromodulator and neuroregulator,^1-3 as such appropriate thyroid functioning is necessary for cognitive performance. This is more prominent during aging, when the brain becomes increasingly dependent on hormonal levels and becomes more sensitive to changes in thyroid function than in younger adults.⁵ Hypothyroidism may cause deterioration of cognitive ability because TH is needed to help regulate the brain glucose-consuming processes for neurotransmission, memory, and other higher functions. The brain becomes increasingly susceptible to thyroid dysfunction in the seventh decade of life.⁶

(Recognition and Treatment of hypothyroidism on next page)

Recognition of Hypothyroidism

Older adults with hypothyroidism have neuropsychological deficits in memory, intelligence, and visuoperceptual or constructive psychomotor skills.^3,5 As such, middle-aged hypothyroid patients tend to present with deficits in attention, learning, memory, and psychomotor speed.⁷ Language comprehension and auditory attention are less affected. People may also present with fatigue, intolerance to cold, dry skin, hoarseness, weight gain, bradycardia, constipation, and menstrual irregularities.⁸ Among elderly patients in particular, the psychiatric aspects may include depression and decline in cognitive function with slow mentation, reduced memory, and inability to concentrate. Less common manifestations are hallucinations and delusions.⁹

Laboratory testing is always performed in people with the above clinical features. Hypothyroidism is confirmed by elevated TSH concentrations and a decrease in free thyroxine levels.¹⁰ People over age 60 are documented with reduced secretion of T4 and T3; yet, serum concentrations of total and free thyroxine remain relatively unchanged, since T4 metabolic degradation is diminished.⁷ Primary degenerative and vascular dementia patients would usually have normal thyroid function.

Treatment of Hypothyroidism

Prescribing TH early in the course of disease can be an effective treatment for patients with a hypothyroid-induced dementia. Therefore, with prompt, appropriate replacement therapy, hypothyroidism-associated neuropsychological and affective alterations can be halted or, potentially, reversed.

Patients with hypothyroidism should receive levothyroxine, the supplemental synthetic thyroid hormone. Adults are typically prescribed a daily loading dose of levothyroxine (1.8 ųg/kg), under close clinical and laboratory observation.¹¹ When provided early in the endocrine dysfunction, this can lead to remission or reduction of cognitive and affective symptoms, through restoration of normal endocrine function and consequent enhancement of monoaminergic brain activity.¹²

Once an appropriate dose has been established by clinical titration, TH assays are monitored every 6 to 12 months to ensure proper treatment. The levothyroxine dose is altered on variables of efficacy, comorbid illness, weight, estrogen use, and patient age.¹¹  When dosages are changed, monitoring should be more frequent.

Levothyroxine treatment may have only partial efficacy at improving dementia. Cognitive defects, especially involving attention and verbal memory can persist in chronically affected patients, even when patients are adequately treated with levothyroxine.¹³

Conclusion

Normal and pathological brain functions in elderly people can be influenced by TH. An early hypothyroidism diagnosis, with prompt treatment, is important to reset hormonal concentrations and prevent tissue damage caused by metabolic dysfunction. Cognitive and affective status can improve and the brain may be protected against advancing dementia. Late intervention diminishes the prognosis.

References

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Affiliations: Department of Psychiatry, University of Louisville School of Medicine, Louisville, KY

Disclosures: The authors report no relevant financial relationships.