. 2018 Dec 21;26(1):45–65. doi: 10.1097/GME.0000000000001171

TABLE 5.

Papers with full differentiation (main cognitive and brain outcomes only)

Citation	Study	Age range, menopausal definition, and assessment	Cognitive and brain assessment	Main cognitive and brain outcomes	Category explanation
Jacobs EG, et al. J Neurosci. 2016 Sep 28;36(39):10163-10173.	• n = 186 • Four groups: men (n = 94), premenopausal (n = 32), perimenopausal (n = 29), postmenopausal (n = 31) • New England Family Study • Blood E₂, progesterone, and testosterone • Functional neuroimaging	• Range = 45-55 y • Cycling and postmenopause (STRAW stage +1c) • Menopause defined by STRAW + 10 menstrual cycle characteristics and FSH levels	• American Adult Reading Test • Controlled Oral Word Fluency • Digit Span Backwards • Verbal Fluency Neuroimaging • 12-item FNAME • 6-trial Selective Reminding Test • Verbal encoding task	All: lower E₂ correlated with lower left hippocampal activity Postmenopausal: lower task-related left hippocampal activity; increased task-related bilateral hippocampal connectivity compared to pre-, peri-, and men. Low-performers had the greatest task related hippocampal connectivity	TofM: “menopause transition,” tight age, and LMP range suggest spontaneous menopause, TSM and AatM: STRAW stages and controlled for chronological age.
Jacobs EG, et al. Cereb Cortex. 2017 May 1;27(5):2857-2870.	• n = 141 • Four groups: men (n = 62), premenopausal (n = 26), perimenopausal (n = 23), postmenopausal (n = 20) • New England Family Study • Blood E₂, progesterone, testosterone, LH and FSH levels • Functional neuroimaging	• Range = 46-55 y • see above citation for details	• Digit Span Backwards • Controlled Oral Word Fluency • Verbal Fluency • American Adult Reading Test Neuroimaging • Verbal working memory n -back task	Behavior None Neuroimaging All groups: higher E₂ and progesterone correlated with task-related hippocampal deactivation Post & -Peri>Pre: task-related DLPFC and hippocampal activity Post > Pre: task-related DLPFC connectivity	TofM: “menopause transition,” tight age, and LMP range suggest spontaneous menopause, TSM and AatM: STRAW stages and controlled for chronological age.
Kantarci K, et al. J Alzheimers Dis. 2016;53(2):547-556.	• n = 68 • 3 groups: CEE (n = 17), transdermal E₂ (n = 21), or placebo (n = 30) for 4 y • Kronos Early Estrogen Prevention Study • Tested 3 y after HT completion • Structural neuroimaging	• Range = 52-65 y • 5-36 mo since LMP • Induced menopause excluded	• CVLT • Digit Span • NYU Paragraphs • Stroop test • Trail Making Test A and B • Venton Visual Retention Test • Verbal Fluency • Wechsler Digit Symbol Coding • Wechsler Letter-Number Sequencing	CEE: lower verbal learning and memory scores than placebo, no association with Aβ plaques	TofM: Induced menopause excluded, TSM and AatM: Tight age range.
Karim R, et al. J Am Geriatr Soc. 2016;64(12):2448-2456.	• n = 830 • WISH and ELITE study • Reproductive history	• Range = 41-92 y • 6+ mo since LMP • Induced menopause excluded	• Block Design • Boston Naming Test • CVLT • East Boston Memory Test • Faces I and II • Judgment of Line Orientation • Letter-Number Sequencing • Shipley Abstraction scale • Symbol Digit Modalities Test • Trail Making Test • Verbal Fluency	Longer reproductive period: greater global cognition and executive function	TofM: Induced menopause excluded, TSM and AatM: length of reproductive period.
Karlamangla AS, et al. PLoS One. 2017;12(1):e0169008.	• n = 2,124 • Followed annually into menopause for at least 3 y, up to 12 y	• Mean = 54 y (no range) • Premenopause (at least one menstrual period in last 3 mo) • Average age at LMP: 52 y	• Digit Span Backwards • East Boston Memory Test • Symbol Digit Modalities Test	With each year after LMP, processing speed and delayed verbal memory declined	TofM: interim hysterectomy and/or oophorectomy before spontaneous menopause covaried. TSM: independent variable, AatM: combination of TSM and chronological age.
Kurita K, et al. Fertil Steril. 2016 Sep 1;106(3):749-756.e2	• n = 926 (n = 123 with bilateral oophorectomy) • Combined data from WISH, ELITE, and B-Vitamin Atherosclerosis Intervention Trial (BVAIT) • Follow-up average after 3 y	• Mean = 60.7 y (no range) • 6+ mo since LMP • Unilateral oophorectomy excluded • Induced menopause (bilateral oophorectomy): WISH = 10.7%, ELITE = 12.6%, BVAIT = 20.1%	See Karim et al, 2016	Oophorectomy after spontaneous menopause: No correlation with cognitive performance Oophorectomy after 45: lower performance in verbal learning at baseline compared with spontaneous menopause Oophorectomy before 45: decline in semantic and visual memory	TofM and AatM: analyzed age at surgery/surgery after menopause. TSM: combination of AatM and chronological age.
Rentz DM, et al. Menopause. 2017 Apr;24(4):400-408.	• n = 203 • Four groups: men (n = 106), premenopausal (n = 36), perimenopausal (n = 29), postmenopausal (n = 32) • New England Family Study • Blood E₂, progesterone, and testosterone levels • Functional neuroimaging	• Range = 46-55 y • See Jacobs et al., 2016 for details	• American Adult Reading Test • Controlled Oral Word Fluency • Digit Span Backwards • Verbal fluency Neuroimaging • FNAME • Selective Reminding Test	All: higher E₂ levels associated with better selective reminding test and FNAME performance Pre- and peri-menopausal: better than postmenopausal women on FNAME and selective reminding task	TofM: “menopause transition,” tight age, and LMP range suggest spontaneous menopause, TSM and AatM: STRAW stages and controlled for chronological age.
Serrano-Guzmán M, et al. Menopause. 2016 Sep;23(9):965-973.	• n = 52 (n = 27 intervention) • Guided dance therapy vs self-directed treatment • Tested at baseline and after 2 mo	• Mean = 69.3 y (no range) • 1+ y since LMP • Diagnosed with spontaneous menopause by clinician	• Quality of Life questionnaire • Timed get-up-and-go task	Intervention: improvement in cognitive timed up-and-go task compared to controls.	TofM, TSM, AatM: all participants spontaneous menopause.
Triantafyllou n, et al. Climacteric. 2016;19(4):393-399.	• n = 39 • Seeking treatment for subjective memory complaints • Blood E₂ and FSH	• Mean = 58.7 y (no range) • 1+ y since LMP • FSH>25 mIU/mL • E₂<50 pg/mL • TSM: between 1 and 33 y (average 10 y) • Induced menopause excluded	Objective • Brief Visuospatial Memory Test • Clock Drawing Test • HVLT • MMSE Subjective • Greene's Climacteric scale	Psychological symptom severity and low circulating E₂ correlated with lower MMSE and visuo-spatial memory. Vasomotor symptom severity correlated with worse total, delayed, and retained verbal learning.	TofM: POI and induced menopause excluded, TSM: covaried, AatM: TSM and chronological age.

AatM, age at menopause; CEE, Conjugated Equine Estrogens; CVLT, California Verbal Learning Test; DLPFC, dorsolateral prefrontal cortex; ELITE, Early vs Late Intervention Trial of Estradiol study; E₂, 17β-estradiol; FNAME, Face Name Associative Memory Exam; FSH, follicle-stimulating hormone; LH, luteinizing hormone; LMP, last menstrual period; NYU, New York University; POI, premature ovarian insufficiency; STRAW, Stages of Reproductive Aging Workshop; TofM, types of menopause; TSM, time since menopause; WISH, Women's Isoflavone Soy Health study.