TABLE 4.
Articles with partial 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 |
| Bojar I, et al. Med Sci Monit. 2016c Sep;22:3469-3478. | • n = 210 • Blood FSH and E2 levels • ERα genotyping: GG (n = 35), AA (n = 71), AG (n = 104) | • Range = 50-65 y • 2+ y since LMP • FSH >30 mIU/mL • Age at LMP: 42-56 y | See Bojar et al., 2016a | No effect of AatM on cognition. ERα GG polymorphism: reduced memory and processing speed compared to ERαAA or AG (AatM not factored) | No information on TofM, TSM accounted for by analyzing chronological age and AatM. |
| Dumas JA, et al. Menopause. 2017 Feb;24(2):163-170. | • n = 18 • Testing 3 d of pharmacological regimen consisting of: bromocriptine (DA agonist), haloperidol (DA blocker), and placebo • Blood E2, estrone, and testosterone levels • Functional neuroimaging | • Range = 52-59 y • 1+ y since LMP (stages +1 and +2 of STRAW +10 staging) • TSM: Average 5.5 y since LMP • Induced menopause excluded | • Verbal n -back task | Behavioral None Neuroimaging Dopaminergic stimulation: increased brain activation in precentral gyrus and inferior parietal lobule compared to dopaminergic blockade. | TofM: Induced menopause excluded. TSM reported but not analyzed. No information on AatM. |
| Espeland MA, et al. J Gerontol A Biol Sci Med Sci. 2017 Jun;72(6):838-845. | • n = 4,256 • 2 cohorts: n = 1,376 recent menopause (701 on HT); n = 2,880 late menopause (1,402 on HT) • WHIMS - Younger Women and Cognitive Outcome Cohorts • Tested a mean 6.8 y after HT trial | • Range = 50-54 y and 65-79 y • Menopause undefined | • Digit Span Test • East Boston Memory Test • Oral Trail Making Test • Telephone Interview for Cognitive Status-modified • Verbal Fluency | HT in late menopause: decrements in global cognitive function, working memory, and executive function | No information on TofM, no specific information on TSM but recent vs late covaried, No information on AatM. |
| Hampson E, et al. Psychoneuroendocrinology. 2016 Feb;64:99-107. | • n = 99 (n = 64 on HT) • Salivary cortisol before testing and halfway through, randomized by time of day | • Range = 45-65 y • 1+ y since LMP • Age at LMP: 40-58 y | • CVLT • Digit Span Forward task | Higher cortisol levels associated with better recall and fewer memory errors. | No information on TofM or TSM, AatM reported for each HT group, number of women with early menopause was equal across groups. |
| Henderson VW, et al. Neurology. 2016;87(7):699-708. | • n = 567 • Two cohorts: n = 234 recent menopause (121 on HT); n = 333 late menopause (163 on HT) • Early versus Late Intervention Trial with Estradiol • 3 time points: baseline, 2.5 y, and 5 y | • Range = 41-84 y • Recent menopause: 6 mo-6 y since LMP • Late menopause: 10+ y since LMP • Serum E2<25 pg/mL • Induced menopause (bilateral oophorectomy): recent HT = 4.1%, recent placebo = 1.8%, late HT = 14.1%, late placebo = 17% | • 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 | Induced and spontaneous menopause: no difference in global cognition | TofM: subgroup analysis of spontanous vs induced menopause, TSM, AatM reported for each HT group, number of women with early menopause was equal across groups but not controlled for in subgroup analysis. |
| Imtiaz B, et al. J Alzheimers Dis. 2017;56(2):453-458. | • n = 731 • Three groups: HT never (n = 488), HT for ≤5 y (n = 116), HT for >5 y (n = 127) • 2 timepoints: baseline and follow-up after mean of 8.3 y | • Range = 65-79 y • Menopause undefined • Induced menopause (hysterectomy with bilateral oophorectomy): HT never = 11.9%; HT ≤5 yrs = 21.9%; HT>5 yrs = 27.8% | • Bimanual Purdue Pegboard Test • Category Fluency • Immediate Word Recall • Letter-Digit Substitution Test • MMSE • Stroop test | HT use >5 y: better episodic memory at baseline but not follow-up | TofM: Gynecological surgery analysis stratified by type of surgery, no information on TSM or AatM. |
| Janelsins MC, et al. J Clin Oncol. 2017 Feb 10;35(5):506-514. | • n = 945 (n = 505 with invasive breast cancer) • 3 time points: prechemotherapy, within 4 wk of chemotherapy end, 6 mo after second time point. | • Range = 22-81 y • Menopause undefined • Pre- and postmenopausal • Induced menopause (udefined): menopausal cancer patients = 8.8%, menopausal noncancer controls = 10.4% | • Functional Assessment of Cancer Therapy - Cognition scale | Chemotherapy: worse cognition compared to controls. Postmenopausal status pre-chemotherapy predicted perceived cognitive impairment. | TofM: pre, peri, post, induced analyzed, no information on TSM or AatM. |
| Lal C, et al. Sleep Breath. 2016 May;20(2):621-626. | • n = 254 (n = 154 high risk for obstructive sleep apnea syndrome) | • Range = 45-60 y • 1-5 y since LMP • Induced menopause excluded | Mail-In Cognitive Function Screening Instrument | Obstructive sleep apnea syndrome: worse objective cognition and higher diagnosis of depression | TofM: Induced menopause excluded, no information on TSM or AatM. |
| Li FD, et al. J Alzheimers Dis. 2016;49(1):139-47. | n = 4,796 • Reproductive period: age at menopause minus age at menarche. • Reproductive history included number of pregnancies, contraceptive use, and regularity of periods • Lifetime estrogen exposure effect on cognition | • Mean = 69.8 y (all participants >65; no range) • Menopause undefined • Average age at LMP: 49.3 y | • Chinese-language version of the MMSE | Lower lifetime estrogen exposure: increased risk of cognitive impairment Use of oral contraceptives: improved cognition. | No information on TofM, TSM: analyzed chronological age and AatM. |
| Rettberg JR, et al. Neurobiol Aging. 2016;40:155-163. | • n = 502 (n = 216 recently menopausal) • ELITE study • 3 metabolic clusters: high blood pressure, healthy, poor • 3 time points: baseline, 2.5 y, and 5 y | • Mean = 60.5 y (no range) • Serum E2<25 pg/mL • Recent menopause: 6 mo-6 y since LMP • Late menopause: 10+ y since LMP • TSM: average high blood pressure = 10.4 y, healthy = 9.9 y, poor = 11.5 y | • 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 | Poor metabolic cluster: lower executive function, global memory, and cognitive performance at baseline All with HT: better global cognition and verbal memory | No information on TofM, TSM: average with recent vs late covaried, no information on AatM. |
| Shanmugan S, et al. Neuropsychopharmacology. 2017 Jan;42(2):437-445. | • n = 14 • Onset of executive function difficulty during menopause • 4 week Lisdexamfetamine trial, 2 week washout, 4 week placebo (counterbalanced) • Functional neuroimaging | • Range = 45-60 y • Perimenopausal and postmenopausal • Postmenopause: 1-5 y since LMP, serum FSH levels >35 IU/L • TSM: average 2.7 y | • Brown Attention Deficit Disorder Scale • Letter n -back task • NYU Paragraph Recall task • Penn Continuous Performance Task Neuroimaging • Fractal n -back task | Behavioral Treatment: improved executive function Neuroimaging Treatment: increased activation in insula and DLPFC, and decreased DLPFC glutamate and glutamine levels Improved executive function correlated with activation of insula and DLPFC | TofM: “menopause transition,” tight age, and LMP range suggest spontaneous menopause, TSM: mean reported but not analyzed. No information on AatM. |
| Unkenstein AE, et al. Menopause. 2016 Dec;23(12):1319-1329. | • n = 130 (n = 40 postmenopausal) | • Range = 40-60 y • Peri and postmenopausal • Menopause: 1+ y since LMP • Induced menopause excluded | Objective • Boston Naming Test • Category fluency • Controlled Oral Word Association Task • Digit Span • Logical Memory • Rey Auditory Verbal Learning Test • Rey Complex Figure Test • Stroop test • Symbol Digit Modality Test • Trail Making Test B • Visual Elevator Counting Subjective • Multifactorial Memory Questionnaire | Objective None Subjective Perimenopausal: worse memory and more frequent memory lapses. | TofM: induced menopause excluded. No information on TSM or AatM. |
| Unkenstein AE, et al. Menopause. 2017 May;24(5):574-581. | • n = 32 • 4-week memory strategies course • 4 time-points: 1 month before course, during course, post-course, 3 mo post-course | • Range = 47-60 y • Perimenopausal and postmenopausal • Perimenopause: self-reported variable menses • Menopause: 1+ y since LMP • Induced menopause excluded | • Multifactorial Memory Questionnaire | Memory course participants: improved memory fewer everyday memory lapses, and increased satisfaction with memory. | TofM: induced menopause excluded. No information on TSM or AatM. |
| Vega JN, et al. Front Neurosci. 2016 Sep 23;10:433. | • n = 31 (n = 15 subjective cognitive complaints) • Functional neuroimaging | • Mean = 56 y (no range) • 1+ y since LMP • Induced menopause excluded | Objective • Brief Cognitive Rating Scale • Mattis Dementia Rating Scale Subjective • CCI Neuroimaging • Selective Reminding Task | Objective and Subjective None Years since menopause: no correlation with CCI Neuroimaging Higher CCI positively correlated with functional connectivity in right middle temporal gyrus, but negatively in left middle frontal gyrus. | TofM: induced menopause excluded. TSM and chronological age analyzed for subjective complaints but not cognitive and brain outcomes; No information on AatM. |
AatM, age at menopause; CCI, Cognitive Complaint Index; CVLT, California Verbal Learning Test; DA, dopamine; DLPFC, dorsolateral prefrontal cortex; E2, 17β-estradiol; ERα=Estrogen Receptor α; FSH, follicle-stimulating hormone; HT, hormone therapy; LMP, last menstrual period; MMSE, Mini-Mental State Exam; STRAW, Stages of Reproductive Aging Workshop; TofM, types of menopause; TSM, time since menopause.