Table 1.

Characteristics of studies included.

Study	Year	Country	Sample size	Women, %	Mean age (s.d.)	Follow-up (years)	Abnormal thyroid status definition	TSH cutoff level (mU/L)	Results	NOS
Kalmijin	2000	Netherlands	1843	61.90	68.8 (7.5)	2.1	Subclinical hypothyroidism: TSH > 4 mU/L, FT4 11–25 pmol/L; subclinical hyperthyroidism: TSH < 0.4 mU/L, FT4 11–25 pmol/L	0.4–4.0	Subclinical hyperthyroidism in the elderly increases the risk of dementia and Alzheimer’s disease.	8
Annerbo	2006	Sweden	93	51.60	64.7 (9.2)	6	/	0.2–4.0	Lower TSH levels were found to be predictive factors of Alzheimer’s disease.	7
de Jong	2006	Netherlands	1077	51.20	72.3 (7.4)	5.5	Subclinical hypothyroidism: TSH > 4.3 mU/L, FT4 0.85–1.94 ng/dL, T3 92.8–162.9 ng/dL; subclinical hyperthyroidism: TSH < 0.4 mU/L, FT4 0.85–1.94 ng/dL, T3 92.8–162.9 ng/dL	0.4–4.3	TSH and thyroid hormones were not associated with the risk of dementia or Alzheimer’s disease.	8
Tan	2008	USA	1864	59.00	71 (7)	12.7	/	0.5–5.0	Low and high thyrotropin levels were associated with an increased risk of incident Alzheimer’s disease in women but not in men.	9
Annerbo	2009	Sweden	200	79.50	81.0 (4.6)	6.7	/	0.2–4.0	TSH is not involved in the development of Alzheimer’s disease.	7
de Jong	2009	Hawaii	665	0	78.1 (5.7)	4.7	Subclinical hypothyroidism: TSH > 4.3 mU/L, FT4 0.85–1.94 ng/dL; subclinical hyperthyroidism: TSH < 0.4 mU/L, FT4 0.85–1.94 ng/dL	0.4–4.3	No associations were found for TSH and dementia or Alzheimer’s disease.	7
Vadivelo	2011	UK	12115	77.40	66.2 (16.4)	5.6	Subclinical hyperthyroidism: TSH ≤ 0.4 mU/L, FT4 10–25 pmol/L or total T4 65–155 nmol/L and total T3 0.9–2.6 nmol/L	0.4–4.0	Subclinical hyperthyroidism patients were associated with an increased risk of dementia.	9
Forti	2012	Italy	660	52.90	73.3 (6.0)	3.8	Subclinical hypothyroidism: TSH > 4.50 mU/L, FT4 10.3–25.7 pmol/L	0.45–4.5	Baseline TSH was not related to the risk of developing Alzheimer’s disease, but high TSH was associated with an increased risk of vascular dementia.	7
Study	Year	Country	Sample size	Women, %	Mean age (s.d.)	Follow-up (years)	Abnormal thyroid status definition	TSH cutoff level (mU/L)	Results	NOS
Yeap	2012	Australia	3401	0	76.8 (3.5)	5.9	Subclinical hypothyroidism: TSH > 4.0 mU/L, FT4 ≥ 10 pmol/L	0.4–4.0	There was no association between TSH quartiles and incident dementia.	8
Formiga	2014	Spain	307	54.60	85.0 (0.0)	3	Subclinical hypothyroidism: TSH > 5.0 mU/L, FT4 0.85–1.94 ng/dL; subclinical hyperthyroidism: TSH < 0.25 mU/L, FT4 0.85–1.94 ng/dL	0.25–5.0	Subclinical hypo- and hyperthyroidism were not associated with an increased risk of dementia.	5
Moon	2014	Korea	313	50	72.5 (6.9)	5	/	0.4–4.1	Lower serum TSH level within the reference range was independently associated with the risk of dementia in elderly subjects.	8
Cappola	2015	USA	2843	56.20	74.5 (5.1)	17	/	0.45–4.5	Individuals with TSH in the fourth quartile had a 9.6 per 1000 person-year lower incidence of dementia.	9
Chaker	2016	Netherlands	9446	56.70	64.9 (9.7)	8	/	0.4–4.0	High and high-normal thyroid function is associated with increased dementia risk.	9
Aubert	2017	USA	2558	51.80	75.1 (2.8)	9	Subclinical hypothyroidism: TSH > 4.50 mU/L, FT4 10.3–23.2 pmol/L; subclinical hyperthyroidism: TSH < 0.45 mU/L, FT4 10.3–23.2 pmol/L	0.45–4.49	Among older adults, subclinical hyperthyroidism with a TSH < 0.10 mU/L was associated with a higher risk of dementia.	9
George	2019	USA	12481	56	57 (5.7)	21.9	Clinical hypothyroidism: TSH > 5.1 mU/L, FT4 < 0.85 ng/dL; subclinical hypothyroidism: TSH > 5.1 mU/L, FT4 0.85–1.4 ng/dL; subclinical hyperthyroidism: TSH < 0.56 mU/L, FT4 0.85–1.4 ng/dL; clinical hyperthyroidism: TSH < 0.56 mU/L, FT4 > 1.4 ng/dL	0.56–5.1	Subclinical hypothyroidism was associated with a reduced risk of dementia, whereas overt hyperthyroidism, particularly very elevated FT4, was associated with an increased risk of dementia.	9
Quinlan	2019	Sweden	302	54	65.0 (7.8)	2.8	/	0.3–4.2	TSH did not associate with dementia.	6
Folkestad	2020	Denmark	Danish National Patient registry (DNPR) cohort: 280640 OPENTHYRO register cohort: 13440	/	DNPR cohort: 65 (54–75) OPENTHYRO register cohort: 62 (49–74)	DNPR cohort: 7.2 OPENTHYRO register cohort: 7.3	Subclinical hyperthyroidism: TSH < 0.3 mU/L, T4 < 135.0 nmol/L, T3 < 2.2 nmol/L; clinical hyperthyroidism: TSH < 0.3 mU/L, T4 > 135.0 nmol/L and/or T3 > 2.2 nmol/L	0.3–4.0	Every 6 months of decreased TSH was associated with an increased risk of dementia by 16%, compared to individuals with normal TSH.	9

FT3, free triiodothyronine; FT4, free thyroxine; NOS, score of Newcastle–Ottawa Scale; TSH, thyroid-stimulating hormone.