%0 Journal Article %J J Alzheimers Dis %D 2017 %T Association of Kidney Function Biomarkers with Brain MRI Findings: The BRINK Study. %A Vemuri, Prashanthi %A Knopman, David S %A Jack, Clifford R %A Lundt, Emily S %A Weigand, Stephen D %A Zuk, Samantha M %A Thostenson, Kaely B %A Reid, Robert I %A Kantarci, Kejal %A Slinin, Yelena %A Lakshminarayan, Kamakshi %A Davey, Cynthia S %A Murray, Anne %X

BACKGROUND: Chronic kidney disease (CKD) studies have reported variable prevalence of brain pathologies, in part due to low inclusion of participants with moderate to severe CKD.

OBJECTIVE: To measure the association between kidney function biomarkers and brain MRI findings in CKD.

METHODS: In the BRINK (BRain IN Kidney Disease) study, MRI was used to measure gray matter volumes, cerebrovascular pathologies (white matter hyperintensity (WMH), infarctions, microhemorrhages), and microstructural changes using diffusion tensor imaging (DTI). We performed regression analyses with estimated glomerular filtration rate (eGFR) and urine albumin to creatinine ratio (UACR) as primary predictors, and joint models that included both predictors, adjusted for vascular risk factors.

RESULTS: We obtained 240 baseline MRI scans (150 CKD with eGFR <45 in ml/min/1.73 m2; 16 mild CKD: eGFR 45-59; 74 controls: eGFR≥60). Lower eGFR was associated with greater WMH burden, increased odds of cortical infarctions, and worsening diffusion changes throughout the brain. In eGFR models adjusted for UACR, only cortical infarction associations persisted. However, after adjusting for eGFR, higher UACR provided additional information related to temporal lobe atrophy, increased WMH, and whole brain microstructural changes as measured by increased DTI mean diffusivity.

CONCLUSIONS: Biomarkers of kidney disease (eGFR and UACR) were associated with MRI brain changes, even after accounting for vascular risk factors. UACR adds unique additional information to eGFR regarding brain structural and diffusion biomarkers. There was a greater impact of kidney function biomarkers on cerebrovascular pathologies and microstructural brain changes, suggesting that cerebrovascular etiology may be the primary driver of cognitive impairment in CKD.

%B J Alzheimers Dis %V 55 %P 1069-1082 %8 2017 %G eng %N 3 %1 http://www.ncbi.nlm.nih.gov/pubmed/27767995?dopt=Abstract %R 10.3233/JAD-160834 %0 Journal Article %J J Alzheimers Dis %D 2016 %T Early Postmenopausal Transdermal 17β-Estradiol Therapy and Amyloid-β Deposition. %A Kantarci, Kejal %A Lowe, Val J %A Lesnick, Timothy G %A Tosakulwong, Nirubol %A Bailey, Kent R %A Fields, Julie A %A Shuster, Lynne T %A Zuk, Samantha M %A Senjem, Matthew L %A Mielke, Michelle M %A Gleason, Carey %A Jack, Clifford R %A Rocca, Walter A %A Miller, Virginia M %X

BACKGROUND: It remains controversial whether hormone therapy in recently postmenopausal women modifies the risk of Alzheimer's disease (AD).

OBJECTIVE: To investigate the effects of hormone therapy on amyloid-β deposition in recently postmenopausal women.

METHODS: Participants within 5-36 months past menopause in the Kronos Early Estrogen Prevention Study, a randomized, double blinded placebo-controlled clinical trial, were randomized to: 1) 0.45 mg/day oral conjugated equine estrogens (CEE); 2) 50μg/day transdermal 17β-estradiol; or 3) placebo pills and patch for four years. Oral progesterone (200 mg/day) was given to active treatment groups for 12 days each month. 11C Pittsburgh compound B (PiB) PET imaging was performed in 68 of the 118 participants at Mayo Clinic approximately seven years post randomization and three years after stopping randomized treatment. PiB Standard unit value ratio (SUVR) was calculated.

RESULTS: Women (age = 52-65) randomized to transdermal 17β-estradiol (n = 21) had lower PiB SUVR compared to placebo (n = 30) after adjusting for age [odds ratio (95% CI) = 0.31(0.11-0.83)]. In the APOEɛ4 carriers, transdermal 17β-estradiol treated women (n = 10) had lower PiB SUVR compared to either placebo (n = 5) [odds ratio (95% CI) = 0.04(0.004-0.44)], or the oral CEE treated group (n = 3) [odds ratio (95% CI) = 0.01(0.0006-0.23)] after adjusting for age. Hormone therapy was not associated with PiB SUVR in the APOEɛ4 non-carriers.

CONCLUSION: In this pilot study, transdermal 17β-estradiol therapy in recently postmenopausal women was associated with a reduced amyloid-β deposition, particularly in APOEɛ4 carriers. This finding may have important implications for the prevention of AD in postmenopausal women, and needs to be confirmed in a larger sample.

%B J Alzheimers Dis %V 53 %P 547-56 %8 2016 May 07 %G eng %N 2 %1 http://www.ncbi.nlm.nih.gov/pubmed/27163830?dopt=Abstract %R 10.3233/JAD-160258