Endocrine dysfunction and cognitive impairment.

Dementia is a highly prevalent chronic disease among the older population, affecting more than 50 million people worldwide and representing a huge healthcare, social and economic burden. Dementia, and in particular Alzheimer's disease, prevalence is expected to raise within the next few years. Unfortunately, no disease-modifying therapies are available so far, despite a plethora of clinical trials targeting the hallmarks of Alzheimer's disease. Given these premises, it appears crucial to address not only the neuropathological correlates of the disease, but also the modifiable risk factors. Among them, evidence suggest a role of the endocrine system not only in the brain development, but also in the maintenance of its health, having neurotrophic, antioxidant and metabolic functions crucial for the cognitive abilities. This review focuses on the evidence evaluating the impact of the endocrine systems, in particular thyroid function, insulin resistance, parathyroid hormone, vitamin D and sexual hormones on cognitive status. Results from epidemiological, preclinical and some clinical studies demonstrated the link between thyroid, parathyroid hormone and vitamin D and cognitive status, between diabetes, and insulin resistance in particular, and dementia, between sexual and adrenal hormones, particularly estrogen variation at menopause, and cognitive decline. The growing interest on the modifiable risks factors of cognitive decline increased the knowledge about the complex interplay of endocrine systems and cognition, highlighting the need and the usefulness of a multidisciplinary approach to the prevention of a complex and devastating disease.

Hypothyroidism in the Elderly: Who Should Be Treated and How?

Hypothyroidism is among the most frequent chronic diseases in the elderly, and levothyroxine (l-T4) is worldwide within the 10 drugs more prescribed in the general population. Hypothyroidism is defined by increased serum thyroid-stimulating hormone (TSH) values and reduced circulating free thyroid hormones, whereas subclinical hypothyroidism (sHT) is characterized by free hormone fractions within the normal ranges and has been divided into two classes, depending on circulating TSH levels (above or below 10 mIU/L). Given that during aging, a natural trend toward higher values of circulating TSH has been reported, it is necessary to verify carefully the diagnosis of sHT to tailor an appropriate follow-up and ad hoc therapy, avoiding unnecessary or excessive treatment. In the current review, we evaluate the state of the art on hypothyroidism in the elderly with special focus on the effect of sHT on cognition and the cardiovascular system function. We also summarize the recommendations for a correct diagnostic workup and therapeutic approach to older people with an elevated TSH value, with special attention to the presence of frailty, comorbidities, and poly therapy. In conclusion, personalized therapy is crucial in good clinical practice, and in the management of older patients with sHT, multiple factors must be considered, including age-dependent TSH cutoffs, thyroid autoimmunity, the burden of comorbidities, and the possible presence of frailty. l-T4 is the drug of choice for the treatment of hypothyroid older people, but the risk of overtreatment, potential adverse drug reactions, and patient compliance should always be considered and thyroid status periodically reassessed.