Menopause and cognitive complaints: are ovarian hormones linked with subjective cognitive decline?

Subjective cognitive decline (SCD) and the loss of ovarian hormones after menopause have been independently linked to later-life Alzheimer's disease (AD). The objective of this review was to determine whether menopause and the loss of ovarian hormones contribute to cognitive complaints and SCD in women. This would suggest that SCD at the menopausal transition might be an important marker of eventual cognitive decline and AD. We conducted a literature search using PubMed, PsycINFO and Web of Science in July 2020. All English-language studies assessing SCD and cognitive complaints with respect to menopause and ovarian hormones were included. A total of 19 studies were included. Studies found that cognitive complaints increased across the menopause transition and were associated with reductions in attention, verbal and working memory, and medial temporal lobe volume. Women taking estrogen-decreasing treatments also had increased cognitive complaints and reduced working memory and executive function. The current literature provides impetus for further research on whether menopause and the loss of ovarian hormones are associated with cognitive complaints and SCD. Clinicians may take particular note of cognitive complaints after menopause or ovarian hormone loss, as they might presage future cognitive decline.

Hearing loss is associated with gray matter differences in older adults at risk for and with Alzheimer's disease.

Using data from the COMPASS-ND study we investigated associations between hearing loss and hippocampal volume as well as cortical thickness in older adults with subjective cognitive decline (SCD), mild cognitive impairment (MCI), and Alzheimer's dementia (AD). SCD participants with greater pure-tone hearing loss exhibited lower hippocampal volume, but more cortical thickness in the left superior temporal gyrus and right pars opercularis. Greater speech-in-noise reception thresholds were associated with lower cortical thickness bilaterally across much of the cortex in AD. The AD group also showed a trend towards worse speech-in-noise thresholds compared to the SCD group.

A non-invasive method to produce pressure ulcers of varying severity in a spinal cord-injured rat model.

STUDY DESIGN: Experimental study. OBJECTIVES: The objective of this study was to establish a non-invasive model to produce pressure ulcers of varying severity in animals with spinal cord injury (SCI). SETTING: The study was conducted at the Johns Hopkins Hospital in Baltimore, Maryland, USA. METHODS: A mid-thoracic (T7-T9) left hemisection was performed on Sprague-Dawley rats. At 7 days post SCI, rats received varying degrees of pressure on the left posterior thigh region. Laser Doppler Flowmetry was used to record blood flow. Animals were killed 12 days after SCI. A cardiac puncture was performed for blood chemistry, and full-thickness tissue was harvested for histology. RESULTS: Doppler blood flow after SCI prior to pressure application was 237.808±16.175 PFUs at day 7. Following pressure application, there was a statistically significant decrease in blood flow in all pressure-applied groups in comparison with controls with a mean perfusion of 118.361±18.223 (P<0.001). White blood cell counts and creatine kinase for each group were statistically significant from the control group (P=0.0107 and P=0.0028, respectively). CONCLUSIONS: We have created a novel animal model of pressure ulcer formation in the setting of a SCI. Histological analysis revealed different stages of injury corresponding to the amount of pressure the animals were exposed to with decreased blood flow immediately after the insult along with a subsequent marked increase in blood flow the next day, conducive to an ischemia-reperfusion injury (IRI) and a possible inflammatory response following tissue injury. Following ischemia and hypoxia secondary to microcirculation impairment, free radicals generate lipid peroxidation, leading to ischemic tissue damage. Future studies should be aimed at measuring free radicals during this period of increased blood flow, following tissue ischemia.

Hyperthermia induces injury to the intestinal mucosa in the mouse: evidence for an oxidative stress mechanism.

Loss of the intestinal barrier is critical to the clinical course of heat illness, but the underlying mechanisms are still poorly understood. We tested the hypothesis that conditions characteristic of mild heatstroke in mice are associated with injury to the epithelial lining of the intestinal tract and comprise a critical component of barrier dysfunction. Anesthetized mice were gavaged with 4 kDa FITC-dextran (FD-4) and exposed to increasing core temperatures, briefly reaching 42.4°C, followed by 30 min recovery. Arterial samples were collected to measure FD-4 concentration in plasma (in vivo gastrointestinal permeability). The small intestines were then removed to measure histological evidence of injury. Hyperthermia resulted in a ≈2.5-fold elevation in plasma FD-4 and was always associated with significant histological evidence of injury to the epithelial lining compared with matched controls, particularly in the duodenum. When isolated intestinal segments from control animals were exposed to ≥41.5°C, marked increases in permeability were observed within 60 min. These changes were associated with release of lactate dehydrogenase, evidence of protein oxidation via carbonyl formation and histological damage. Coincubation with N-acetylcysteine protected in vitro permeability during hyperthermia and reduced histological damage and protein oxidation. Chelation of intracellular Ca(2+) to block tight junction opening during 41.5°C exposure failed to reduce the permeability of in vitro segments. The results demonstrate that hyperthermia exposure in mouse intestine, at temperatures at or below those necessary to induce mild heatstroke, cause rapid and substantial injury to the intestinal lining that may be attributed, in part, to oxidative stress.

Comparison of major biocontrol strains of non-aflatoxigenic Aspergillus flavus for the reduction of aflatoxins and cyclopiazonic acid in maize.

Biological control of toxigenic Aspergillus flavus in maize through competitive displacement by non-aflatoxigenic strains was evaluated in a series of field studies. Four sets of experiments were conducted between 2007 and 2009 to assess the competitiveness of non-aflatoxigenic strains when challenged against toxigenic strains using a pin-bar inoculation technique. In three sets of experiments the non-aflatoxigenic strain K49 effectively displaced toxigenic strains at various concentrations or combinations. The fourth study compared the relative competitiveness of three non-aflatoxigenic strains (K49, NRRL 21882 from Afla-Guard®, and AF36) when challenged on maize against two aflatoxin- and cyclopiazonic acid (CPA)-producing strains (K54 and F3W4). These studies indicate that K49 and NRRL 21882 are superior to AF36 in reducing total aflatoxin contamination. Neither K49 nor NRRL 21882 produce CPA and when challenged with K54 and F3W4, CPA and aflatoxins were reduced by 84-97% and 83-98%, respectively. In contrast, AF36 reduced aflatoxins by 20% with F3W4 and 93% with K54 and showed no reduction in CPA with F3W4 and only a 62% reduction in CPA with K54. Because AF36 produces CPA, high levels of CPA accumulate when maize is inoculated with AF36 alone or in combination with F3W4 or K54. These results indicate that K49 may be equally effective as NRRL 21882 in reducing both aflatoxins and CPA in maize.

False recognition in Lewy-body disease and frontotemporal dementia.

The primary goal of this study was to evaluate the false recognition phenomenon in persons with frontotemporal dementia (FTD) and those with Lewy-body disease (LBD). Patients with LBD (n=10) or FTD (n=15) and their corresponding controls (n=30) were subjected to the Deese-Roediger-McDermott (DRM) paradigm to induce false recognition. Patients were first presented with items semantically related to a nonpresented critical target. The critical target was later included in a word list shown to patients to assess level of recognition. Both groups of patients showed a reduced level of false recognition of the critical target when controlling for their overall level of false alarms. This reduction was greater in persons with LBD than in those with FTD. Correlational analyses of performance on neuropsychological tests and the DRM variables indicated that the reduced DRM effect was associated with inhibition deficits in patients with LBD and with inhibition deficits and verbal memory in those with FTD. Our results support current models suggesting that these cognitive components contribute to the false recognition effect.

Female sexual dysfunction: evaluation and treatment.

Sexual dysfunction includes desire, arousal, orgasmic and sex pain disorders (dyspareunia and vaginismus). Primary care physicians must assume a proactive role in the diagnosis and treatment of these disorders. Long-term medical diseases, minor ailments, medications and psychosocial difficulties, including prior physical or sexual abuse, are etiologic factors. Gynecologic maladies and cancers (including breast cancer) are also frequent sources of sexual dysfunction. Patient education and reassurance, with early diagnosis and intervention, are essential for effective treatment. Patient history and physical examination techniques, normal sexual responses and the factors that influence these responses, and the application of medical and gynecologic treatments to sexual issues are discussed. Basic treatment strategies, which may be successfully provided by primary care physicians for most sexual dysfunctions, are outlined. Referral can be reserved for patients who do not respond to therapy.

Age-related differences in semantic priming: evidence from event-related brain potentials.

Hasher and Zacks (1988) suggested that aging may affect processes involved in the inhibition of irrelevant information during language processing. Our experiment tested this hypothesis using the N400 event-related brain potential in a priming paradigm and assessed whether older subjects could benefit from the constraints of a sentence context. Twenty older (63 to 88 years) and 20 young (19 to 29 years) subjects read sentences and word pairs. Each final word varied on the degree of relatedness to the preceding context, with some being highly related (BC), moderately related (R), or unrelated (U). Younger subjects showed the expected N400 effect gradient (U > R > BC) in both the sentence and word-pair contexts, while older adults showed no discrimination between the conditions (U = R = BC) for the sentence and limited discrimination (U > BC) for the word pairs. These results support the inhibition-deficit hypothesis, whereby older adults fail to inhibit related items in working memory, and suggest that older adults do not benefit from the constraints of a sentence context.

Oral phentolamine and female sexual arousal disorder: a pilot study.

Female sexual arousal disorder (FSAD) is a highly prevalent problem, although little is known about pathophysiology or treatment of the disorder. Given the potential role of vascular mechanisms, a small pilot study was conducted on the effects of oral phentolamine in menopausal women with FSAD. Six postmenopausal women with a lack of lubrication and with sexual arousal difficulties of at least 6 months duration participated in the study. All subjects received a single dose of oral phentolamine (40 mg) and placebo in a single-blind, dose-escalation design. Dependent variables for the study included vaginal pulse amplitude (VPA), as measured by vaginal photoplethysmography, self-report measures of sexual response, and patient- and physician-based assessments of adverse events. Results indicated a mild, positive effect of phentolamine across all measures of arousal, with significant changes (p < .05) in self-reported lubrication and pleasurable sensations in the vagina. The drug was well tolerated, overall, with few reports of adverse side effects. Further studies are needed to assess the potential value of phentolamine and other vasoactive agents in the treatment of female sexual dysfunction.

The clinical evaluation of dyspareunia.

Strictly defined, dyspareunia means 'pain with intercourse'. The psychiatric DSM-IV subdivides and expands this definition and introduces psychogenic factors into the differential diagnosis. This allows development of a biogenic-psychogenic model, whereby organic or psychological factors can be present separately or in combination, within the disorder. Sexual dysfunctions are estimated to be present in 19-63% of women, with dyspareunia the primary complaint in 8-48%. The clinical evaluation of dyspareunia should include a thorough history and meticulous gynecologic examination. Laboratory or imaging studies should be ordered as warranted by suggestive history or exam findings. Identified causes should be treated and counseling considered. Three clinical dilemmas remain. Firstly, lack of standardization of exam findings; secondly discrepancy between objective physical findings and subjective patient complaints; and thirdly paucity of therapeutic options for patients, especially those with an unclear diagnosis. An integrated psychogenic-biogenic model should be developed and implemented for effective diagnosis and treatment of dyspareunia.

Individual differences in auditory middle latency responses in elderly adults and patients with Alzheimer's disease.

Previous research has suggested that the Pb component of the middle-latency auditory evoked response (MLAER) is differentially abnormal in patients with Alzheimer's disease relative to control subjects. In the present study, this putative abnormality was examined in vertex-recorded MLAERs elicited by monaural stimulation in 14 patients with Alzheimer's disease (six females) and 22 age-matched control subjects (10 females). A sex difference in Pb elicitation was revealed in control subjects; Pb area was twice as large in females than males (P < 0.05). Pb and Pa amplitudes and latencies did not differ between male and female control subjects. Comparisons of Pb between patients and controls were conducted within each sex. There was no main effect of group on Pb area, amplitude, or latency, Pa amplitude was significantly larger in patients than control subjects; there was no group difference in Pa latency. This study did not replicate previous reports of differences in Pb between patients with Alzheimer's disease and elderly control subjects. We demonstrated that Pb elicitation may be unreliable in elderly control subjects and found evidence of a possible sex difference. The effects of inter-subject variables (e.g. age, sex) must be understood more fully before MLAERs can be exploited as meaningful markers of brain dysfunction.

Cognitive deficits in peripheral vascular disease. A comparison of mild stroke patients and normal control subjects.

BACKGROUND AND PURPOSE: Evidence indicates that peripheral vascular disease (PVD) and cerebrovascular disease (CVD) coexist and therefore reflect a generalized pattern of atherosclerotic disease in an individual. Given the known deleterious effects of CVD on cognitive function, it was hypothesized that patients with PVD may have impaired cerebral function due to concomitant but clinically unrecognized CVD. The purpose of this study was to determine whether neuropsychological tests would reveal this potential dysfunction. METHODS: Neuropsychological test scores (n = 25) were compared across three groups: (1) 29 PVD patients (13 amputees, 16 nonamputees), (2) 29 age- and education-matched patients with atherothrombotic brain infarcts (ie, CVD), and (3) 30 age- and education-matched control subjects. RESULTS: PVD patients performed significantly worse (P < .002) than control subjects on eight neuropsychological measures of executive function, attention, and visuopatial function. The pattern and, in certain instances, the magnitude of impairment was highly similar between PVD and CVD subjects. Regression analysis revealed that PVD severity and ischemic heart disease were significant negative predictors of test performance. Depression and atherosclerotic risk factors did not explain neuropsychological deficits after the effects of PVD and ischemic heart disease were considered. CONCLUSIONS: PVD patients exhibit neuropsychological deficits that suggest the presence of mild vascular-related brain dysfunction. Patients with multiple manifestations of generalized atherosclerosis (ie, severe PVD, ischemic heart disease) appear to be particularly at risk. Clinicians should be alert to these potential deficits and to the possibility of further vascular-related cognitive decline.

Grouped data do not tell the whole story: individual analysis of cognitive change after temporal lobectomy.

Studies of group measures of central tendency describe the cognitive sequelae of anterior temporal lobectomy; however, information regarding clinically significant change is scarce. This study examined the frequency of clinically significant variability (i.e., a change score > or = 1 standard deviation from preoperative to postoperative performance) in 50 temporal lobectomy patients (19 left-sided; 31 right-sided). A range of cognitive domains was examined. Most (68%) indices showed no change. Of those that changed, an approximately equivalent number were losses and gains. Such results do not support restricting surgical treatment of epilepsy to avoid major cognitive decline. In right-handers, the observance of material-specific memory decline was variable. Only 36% of right-handers with left-temporal lobectomy showed only postsurgical loss in verbal memory, while 50% showed both losses and gains across several verbal memory measures. Almost 60% of right-temporal lobectomy patients exhibited some verbal memory loss, but only one-third showed nonverbal memory loss. We conclude that group studies identifying material-specific memory loss overestimate the consistency and pervasiveness of the negative effects of temporal lobectomy.

The effects of phonological and semantic features of sentence-ending words on visual event-related brain potentials.

Event-related brain potentials (ERPs) were recorded to terminal words of visually presented sentences that were identical to those used in an auditory modality study examining the effects of phonological and semantic characteristics of words on ERPs (Connolly and Phillips, 1994). Phonological and/or semantic characteristics of terminal words were manipulated in 4 conditions in which: (1) the terminal word was the highest cloze probability ending for the sentence and was thus phonologically and semantically appropriate to the sentence context (e.g., Ray fell down and skinned his knee(s).; (2) the terminal word had the initial phonemic sound of the highest cloze probability sentence-ending word but was semantically anomalous to the context of the sentence (e.g., They sat together without saying a single worm. [word]); (3) the initial phoneme of the terminal word was phonologically unexpected but the word was semantically correct (e.g., The dough was put in the hot pan. [oven]); or (4) the initial phoneme of the terminal word was phonologically unexpected and the word was semantically inappropriate to the sentence context (e.g., Bill jumped into the lake and made a big farm. [splash]). A left fronto-temporally distributed negative peak was observed in the 250-300 msec range to varying degrees in all conditions but was largest in the condition in which terminal words were both phonologically unexpected and semantically inappropriate. A second, parietally distributed, symmetrical negativity (the N400) was found which peaked around 365 msec and was largest in the two conditions involving semantically anomalous terminal words. Results are discussed in terms of modality factors in ERP manifestations of receptive language functions and the implications of ERP modality differences for theories of word recognition.

Event-related potential components reflect phonological and semantic processing of the terminal word of spoken sentences.

Abstract An event-related brain potential (ERP) reflecting the acoustic-phonetic process in the phonological stage of word processing was recorded to the terminal words of spoken sentences. The peak latency of this negative-going response occurred between 270 and 300 msec after the onset of the terminal word. The independence of this response (the phonological mismatch negativity, PMN) from the ERP component known to be sensitive to semantic violations (N400) was demonstrated by manipulating sentence endings so that phonemic and semantic violations occurred together or separately. Four conditions used sentences that ended with (1) the highest Cloze probability word (e.g., "The piano was out of tune."), (2) a word having the same initial phoneme of the highest Cloze probability word but that was, in fact, semantically anomalous (e.g., "The gambler had a streak of bad luggage."), (3) a word having an initial phoneme different from that of the highest Cloze probability word but that was, in fact, semantically appropriate (e.g., "Don caught the ball with his glove."), or (4) a word that was semantically anomalous and, therefore, had an initial phoneme that was totally unexpected given the sentence's context (e.g., "The dog chased our cat up the queen"). Neither the PMN nor the N400 was found in the first condition. Only an N400 was observed in the second condition while only a PMN was seen in the third. Both responses were elicited in the last condition. Finally, a delayed N400 occurred to semantic violations in the second condition where the initial phoneme was identical to that of the highest Cloze probability ending. Results are discussed with regard to the Cohort model of word recognition.

Neuropsychological function in peripheral vascular disease amputee patients.

Approximately 75% of major lower-extremity amputations are the result of peripheral vascular disease (PVD). Factors that predispose a patient to PVD (smoking, hyperlipidemia, diabetes mellitus) are also risk factors for the development of cerebrovascular disease, which could adversely affect rehabilitation. The purpose of this study was to test the hypothesis that cognitive deficits are present in amputee patients with PVD. Fourteen patients with lower-extremity amputations secondary to PVD (4 women, 10 men; mean age = 67.4 years) were recruited from a tertiary-care center for physical rehabilitation. Fourteen community-dwelling healthy volunteers (9 women, 5 men; mean age = 69.9 years) served as age-matched and education-matched controls. To assess a broad range of cognitive function, we administered standard neuropsychological tests of memory and learning, language, praxis, visuospatial skills, and abstract reasoning. PVD patients performed significantly more poorly on certain measures of psychomotor speed (Wechsler Adult Intelligence Scale-Revised Digit Symbol subtest) and problem solving/abstract reasoning (Modified Card Sorting Test) relative to controls (using the Bonferroni correction for multiple comparisons, p < .002). There were trends toward poorer patient performance on certain measures of oral fluency, concentration, reasoning, and visuoperceptual organization and constructional skills (p < .01). We propose that these cognitive deficits may be the result of unrecognized concomitant cerebrovascular disease in PVD patients and are part of a generalized pattern of vascular disease. Future research should control affective factors such as stress or depression surrounding amputation and attempt to identify the etiologic or demographic factors that are associated with neuropsychological deficits in patients with PVD.

Event-related potential sensitivity to acoustic and semantic properties of terminal words in sentences.

This experiment was concerned with the effects of phonologically correct masking on the electrophysiological responses to terminal words of spoken sentences differing in contextual constraint. Two event-related potential (ERP) components, the N400 and N200, were recorded to the terminal words of high and low constraint sentences in four conditions. In the Control condition, subjects (Ss) simply attended to the sentences with no explicit task instructions. In the Semantic condition, Ss were required to listen to the stimuli in order to make semantic judgements about the terminal word of each sentence. The Control+Masking condition was identical to the Control condition except for the simultaneous presentation of a masking stimulus. The Semantic+Masking condition had Ss listening to sentences in the presence of masking with the task of making semantic judgements about the terminal word of each sentence. ERPs were recorded from Fz, Cz, Pz, T3, and T4 in 10 subjects. Amplitudes of both the N200 and the N400 were sensitive to contextual constraint with larger responses elicited by the terminal words of low constraint sentences. In addition to demonstrating the co-occurrence of the N200 and N400, this experiment highlighted a functional separation between the two components. Masking had no statistically significant effect on N200 latency but N400 latency was delayed in the masked conditions relative to those in the unmasked conditions. It is proposed that the N200 and N400 are manifestations of two different processes; the N200 reflects the acoustic/phonological processing of the terminal word while the N400 reflects the cognitive/linguistic processing. The relationship between the N200 recorded in this experiment and the discrimination N200 is discussed.

The effects of processing requirements on neurophysiological responses to spoken sentences.

Ten English speaking subjects listened to sentences that varied in sentential constraint (i.e., the degree to which the context of a sentence predicts the final word of that sentence) and event-related potentials (ERPs) were recorded during the presentation of the final word of each sentence. In the Control condition subjects merely listened to the sentences. In the Orthographic processing condition subjects merely listened to the sentences. In the Orthographic processing condition subjects decided, following each sentence, whether a given letter had been present in the final word of the preceding sentence. In the Phonological processing condition the subjects judged whether a given speech sound was contained in the terminal word. In the Semantic processing condition subjects determined whether the final word was a member of a given semantic category. A previous finding in the visual modality that the N400 component was larger in amplitude for low constraint sentence terminations than for high was extended to the auditory modality. It was also found that the amplitude of a N200-like response was similarly responsive to contextual constraint. The hypothesis that N400 amplitude would vary significantly with the depth of processing of the terminal word was not supported by the data. The "N200" recorded in this language processing context showed the classic frontocentral distribution of the N200. The N400 to spoken sentences had a central/centroparietal distribution similar to the N400 in visual modality experiments. It is suggested that the N400 obtained in these sentence contexts reflects an automatic semantic processing of words that occurs even when semantic analysis is not required to complete a given task. The cooccurrence and topographical dissimilarity of the "N200" and N400 suggest that the N400 may not be a delayed or a generic N200.