Serum SHBG Levels are not Associated with Longitudinal Cognitive Decline in Mild Cognitive Impairment

Lin, Katherine; Rundel, Colin; Doraiswamy, P. Murali

doi:10.3233/jad-160513

Cited by 4 publications

(7 citation statements)

References 25 publications

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“…Despite serum SHBG levels being often elevated in females [19,23], we did not observe such changes in CSF, which may indicate that sex related SHBG differences might be more pronounced in blood than in CSF [16]. The lack of association of CSF SHBG with CSF YKL-40 or p/tTau ratio suggests that SHBG is not related to neuroinflammatory processes or Tau proteostasis.…”

Section: Discussioncontrasting

confidence: 74%

“…Interestingly, such association was likely driven by the FTLD-Tau, which showed a correlation coefficient considerably stronger than the FTLD-TDP group (−0.38 vs. −0.02). Previous studies have shown that not only SHBG but also other hormones (e.g., estrogen, free thyroxin or thyroidstimulating hormone) are associated with MMSE [22,23], suggesting that changes in the whole hypothalamic-pituitary (HP) axes may influence memory function and the risk of dementia or AD [24,25]. This is supported by different neuropathological and imaging studies, highlighting the importance of HP dysfunction (e.g., body weight, circadian rhythm, sleep) in AD pathophysiology [25].…”

Section: Discussionmentioning

confidence: 99%

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Sex Hormone-Binding Globulin (SHBG) in Cerebrospinal Fluid Does Not Discriminate between the Main FTLD Pathological Subtypes but Correlates with Cognitive Decline in FTLD Tauopathies

et al. 2021

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Biomarkers to discriminate the main pathologies underlying frontotemporal lobar degeneration (FTLD-Tau, FTLD-TDP) are lacking. Our previous FTLD cerebrospinal fluid (CSF) proteome study revealed that sex hormone-binding globulin (SHBG) was specifically increased in FTLD-Tau patients. Here we investigated the potential of CSF SHBG as a novel biomarker discriminating the main FTLD pathological subtypes. SHBG was measured in CSF samples from patients with FTLD-Tau (n = 23), FTLD-TDP (n = 29) and controls (n = 33) using an automated electro-chemiluminescent immunoassay. Differences in CSF SHBG levels across groups, as well as its association with CSF YKL40, pTau181/total-Tau ratio and cognitive function were analyzed. CSF SHBG did not differ across groups, though a trend towards elevated levels in FTLD-Tau cases compared to FTLD-TDP and controls was observed. CSF SHBG levels were not associated with either CSF YKL40 or the p/tTau ratio. They, however, inversely correlated with the MMSE score (r = −0.307, p = 0.011), an association likely driven by the FTLD-Tau group (r FTLD-Tau = −0.38; r FTLD-TDP = −0.02). CSF SHBG is not a suitable biomarker to discriminate FTLD-Tau from FTLD-TDP.

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Section: Discussioncontrasting

confidence: 74%

Section: Discussionmentioning

confidence: 99%

Sex Hormone-Binding Globulin (SHBG) in Cerebrospinal Fluid Does Not Discriminate between the Main FTLD Pathological Subtypes but Correlates with Cognitive Decline in FTLD Tauopathies

et al. 2021

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“…In older men, with increasing age, the level of SHBG increases. Additionally, compared with healthy aging males, the level of SHBG in elderly AD patients increased significantly (27). However, levels of SHBG have no relationship with cognitive decline in patients with cognitive impairment according to the Alzheimer's Disease Assessment Scale-Cognitive section (28).…”

Section: Relationship Between Decreased Androgens and Impaired Cognitmentioning

confidence: 86%

An Updated Review: Androgens and Cognitive Impairment in Older Men

Cai

Liu

2020

Front. Endocrinol.

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“…A longitudinal cohort study consisting of 514 women and 217 men over 65 years of age found that per SD increase in serum SHBG levels was associated with a 20–30% increased risk for incident dementia with a mean of 5.2 years follow-up [17]. In contrast, findings from the Alzheimer’s Disease Neuroimaging Initiative-1 study involving 371 elderly adults (including 134 women) with mild cognitive impairment reported no significant association between serum SHBG levels and the rate of cognitive decline during 8-year follow-up [18]. The limited sample size, the heterogeneity of participants, or different inclusion criteria in these studies may result in the discrepancy across studies.…”

Section: Discussionmentioning

confidence: 99%

Sex Hormone-Binding Globulin and Risk of Incident Dementia in Middle-Aged to Older Women: Results from the UK Biobank Cohort Study

Huang,

Xu,

Chen

et al. 2023

Neuroendocrinology

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Introduction: The association of serum sex hormone-binding globulin (SHBG) concentrations with dementia risk remains uncertain in middle-aged to older women. We examined associations of serum SHBG levels with incidence of all-cause dementia and its subtypes in middle-aged to older women from the large population-based UK Biobank cohort study. Methods: Serum total SHBG levels were measured by immunoassay. The incidence of all-cause dementia and its subtypes was recorded. Cox proportional hazards models were used to calculate hazard ratios (HR) for main outcomes. Results: Among 171,482 community-dwelling women (mean (SD) age was 59.9 (5.4) years, median follow-up of 11.8 years), 2,368 developed dementia, including 1,088 from Alzheimer's disease (AD), 451 from vascular dementia (VAD), and 1,609 from other dementia. After multivariable adjustments, higher serum SHBG levels were significantly associated with higher risks of all-cause dementia, AD and other dementia (All P<0.05). Compared to those in the lowest quartile of SHBG levels, participants in the highest quartile of SHBG levels had a higher risk of all-cause dementia (HR 1.34; 95% confidence interval [CI] 1.16-1.53), AD (HR 1.32; 95% CI 1.07-1.62), and other dementia (HR 1.44; 95% CI 1.21-1.70). However, this relationship was not significant for VAD (HR 1.16; 95% CI 0.86-1.56). Conclusion: These findings indicated that higher serum SHBG concentrations were independently associated with higher risks of incident all-cause dementia, as well as AD and other dementia among middle-aged to older women. No association was found for VAD.

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Serum SHBG Levels are not Associated with Longitudinal Cognitive Decline in Mild Cognitive Impairment

Abstract: SHBG levels did not influence the rate of cognitive decline in MCI. Further studies to confirm these findings and uncover other potential mechanisms of gender differences in the risk for AD may be warranted.

Cited by 4 publications

References 25 publications

Sex Hormone-Binding Globulin (SHBG) in Cerebrospinal Fluid Does Not Discriminate between the Main FTLD Pathological Subtypes but Correlates with Cognitive Decline in FTLD Tauopathies

Sex Hormone-Binding Globulin (SHBG) in Cerebrospinal Fluid Does Not Discriminate between the Main FTLD Pathological Subtypes but Correlates with Cognitive Decline in FTLD Tauopathies

An Updated Review: Androgens and Cognitive Impairment in Older Men

Sex Hormone-Binding Globulin and Risk of Incident Dementia in Middle-Aged to Older Women: Results from the UK Biobank Cohort Study

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