Association between thyroid function and Alzheimer’s disease: A systematic review

Yet, that study only demonstrated histological hippocampus recovery and did not include additional functional and neurophysiological assessments (103). In addition, elevated thyroid hormone can cause the atrophy of hippocampal and temporal lobe structures (12). As reported, T4 has the ability to trigger long-term depression (LTD) and reduce LTP through a process known as non-genomic, membrane priming effect (52). But the molecular mechanisms of how TH mediates LTD and LTP await further anatomical and pharmacological analysis. It was also found that people diagnosed with hyperthyroidism have a reduced functional connectivity between the hippocampus and the cerebral cortex (53).

Day Thyroid Reset: How To Super Charge Your Thyroid

Up to 20% of the general population may have trouble with standard thyroid medications like Synthroid and levothyroxine, due to genetic variations which can limit how well they convert T4 into T3 (4). I’ve already mentioned previously that hypothyroidism is a potentially reversible cause of dementia and when you stop taking your thyroid medication you are putting yourself into a state of hypothyroidism. Figuring out whether these treatments are right for you or a loved one is no simple process.

• Therefore, we calculated the required number to harm for AD in order to show an absolute effect (Table S5).
• The memory and thinking problems should also be new and persistent (not just occasional lapses), Dr. Schindler says.
• The thyroid regulates metabolism throughout the body through the release of thyroid hormones 1.

The Importance of Thyroid Hormones

A study of patients in Taiwan led by a researcher at Brown University’s Warren Alpert Medical School showed an association between hypothyroidism and dementia in older adults. The authors emphasized that with so many people taking the medication, the findings of the new study that explore the risks are important. Based on the findings, Mammen recommends that TSH levels be checked every year, especially in older patients, to see if their dose of thyroid medication should be changed or stopped.

Lecanemab and donanemab are definitely a step forward, Dr. Lapins says, but not the final word—and a combination of treatments may ultimately be what’s needed. In the clinical trials that led to the two drugs’ approval, some patients were randomly assigned to receive the medication and others were given a placebo. In the lecanemab trial, patients on the drug had a slightly slower decline in memory, thinking skills, and day-to-day functioning than patients given the placebo. Over 18 months, their rate of decline was 27% slower overall—which roughly translates to an extra four to six months without worsening symptoms. Patients on the drug had a 35% slower decline over 18 months compared with the placebo group. Amyloid clumps (often called plaques) start building up early in the Alzheimer’s process.

(3. Hyperthyroidism and DAT

Metabolic changes, initiation of new medications, and diet change can all cause changes in serum thyroid hormone levels that require dose adjustments. Various studies have defined different thyroid-stimulating hormone cutoffs, but the safest thyroid-stimulating hormone concentration was absent. Even in cognitively normal subjects with an abnormal brain βA burden, it usually takes more than 10 years before cognitive decline begins (10). More critically, maintaining homeostasis of thyroid hormone levels within the brain is critical to the proper functioning of the CNS, and even relatively minor deviations in brain hormone levels can cause severe behavioral and cognitive impairment (106). Therefore, it is vital to provide suitable therapy at the best time for each individual patient to prevent and treat cognitive deficits caused by thyroid dysfunction. On one hand, the release of the excitatory neurotransmitter glutamate is decreased (71) and there is also less expression of the postsynaptic neuronal NMDAR subunit NR1 mRNA in the hippocampus (72).

• Few studies reported partial recovery 33,52-54, and even fewer concluded that replacement either slows or stops the progression rather than restoring 53.
• Future prospective studies are essential to confirm and clarify the causal association between thyroid disease and AD.
• Subclinical hypothyroidism was defined as high TSH concentrations but normal blood concentrations of thyroid hormones.
• My recommendation is to take the steps outlined above and do your best to mitigate all risk factors which are known to contribute to the development of dementia.
• Dementia and its subtypes were identified in a multi-step case-finding procedure, described in detail elsewhere 14, 33.
• However, all participants were nondemented at baseline, and their reports of thyroid disease were verified by collateral source interview.

The development of a hypothyroid state is linked with the disease’s progression to the middle and late stages. According to our viewpoint, the loss of compensation for the stress repair response and the expanding lesion are two essential factors that contribute to this. In the first study exploring the hypothalamic-pituitary-thyroid axis in AD, the levels of TRH, TSH and TH were significantly lower in patients with AD (30).

Antithyroid medication improves learning ability in individuals with hyperthyroid dementia, and parts of the frontoparietal lobe with uptake impairments gradually respond to the medicine (99). However, synthroid molecule antithyroid therapy does not completely reverse the symptoms of dementia that occur in hyperthyroid patients. Meanwhile, although functional brain connections and cognitive abilities were improved in hyperthyroid patients treated with antithyroid therapy, they were not totally recovered (101). (1) Studies focused on the relationship of clinical hyperthyroidism and clinical hypothyroidism with the risk of dementia are few.

In a newly published study, hyperthyroidism exacerbates cognitive impairments and increases the accumulation of βA plaques in mice by the activation of neuroinflammation and the induction of brain tissue necroptosis via the RIPK3/MLKL pathway (50). Strengths of this study are its prospective population-based design, the six years of follow-up and the extensive diagnostic work-up for dementia including neuroimaging in most cases. In addition to the diagnosis of a clinical dementia syndrome, neuropathologic markers of AD were available in an autopsy series of the cohort. It should be noted, thyroid hormones were assayed in only one third of all study participants. However, we randomly selected participants for the assessments of thyroid hormones, and did not find any differences between the subgroups with and without thyroid hormone assessments.

Since neurotransmission, memory, and further vital brain functions require the maintenance of normal energy (glucose)-consuming processes, low thyroid function at any age can debilitate cognitive function (7). Given the theoretically increased risk of cognitive decline with thyroid dysfunction, it is conceivable that thyroid diseases can contribute to the pathophysiology of AD. Clinical observations and experimental studies have indicated a relationship between thyroid hormones and AD or its pathology (9–12). However, many previous studies provided inconsistent results owing to small sizes of the data samples, heterogeneous participant characteristics, or cognitive tests of limited sensitivity.

Neuronal synaptic plasticity, also called long-term potentiation, is a crucial mechanism involved in learning and memory 25,26. Several imaging studies showed objective evidence of decreased hippocampal volume with deteriorated memory in hypothyroid patients 27,28. Two studies investigated levothyroxine replacement with placebo on hypothyroid patients 20,21.