Change In Verbal Memory Research Articles

Depresija sergančių asmenų žodinės atminties pokyčiai hospitalizacijos metu

Pažintinių funkcijų, tarp jų ir atminties pokyčių susirgus depresija ir jos metu tyrimų duomenys yra nevienodi – susirgus depresija sutrinka skirtingi atminties komponentai. Šio tyrimo tikslas yra ištirti depresija sergančių asmenų (DSA) žodinės atminties pokyčius hospitalizacijos metu, atsižvelgiant į nerimo ir depresiškumo rodiklius. Tyrime dalyvavo 30 Vilniaus miesto Psichikos sveikatos centre besigydančių DSA, kuriems buvo diagnozuoti įvairaus sunkumo pasikartojantys arba vienkartiniai depresijos epizodai(6 vyrai ir 24 moterys, kurių amžius 21–79 m. (M = 58,17; SD = 14,65)), gaunantys antidepresantus. Tyrime taip pat dalyvavo 30 atitinkamo amžiaus, lyties ir išsimokslinimo sveikų asmenų (SA), kurių amžius – 21–84 m. (M = 58,30; SD = 14,71). Naudojant Taisytą Hopkinso žodinės atminties testą (HVLT-R) bei Depresijos ir nerimo sutrikimų vertinimo instrumentą (HAD), hospitalizacijos pradžioje ir pabaigoje vertinta pacientų žodinė atmintis ir depresiškumo bei nerimo lygis. Nustatyta, kad DSA grupė, palyginti su SA, hospitalizacijos pradžioje pasižymėjo prastesniu betarpišku ir uždelstu atgaminimu. Po hospitalizacijos DSA suminis ir uždelstas atgaminimas pagerėjo. Prastesni DSA atminties rezultatai susiję su didesniu depresiškumu ir nerimu tik hospitalizacijos pabaigoje. Norint išsamiau nagrinėti pažintinių funkcijų ir depresijos kismo hospitalizacijos metu sąveikas, reikia tolesnių tyrimų.

Temporal lobe surgery in childhood and neuroanatomical predictors of long-term declarative memory outcome.

The temporal lobes play a prominent role in declarative memory function, including episodic memory (memory for events) and semantic memory (memory for facts and concepts). Surgical resection for medication-resistant and well-localized temporal lobe epilepsy has good prognosis for seizure freedom, but is linked to memory difficulties in adults, especially when the removal is on the left side. Children may benefit most from surgery, because brain plasticity may facilitate post-surgical reorganization, and seizure cessation may promote cognitive development. However, the long-term impact of this intervention in children is not known. We examined memory function in 53 children (25 males, 28 females) who were evaluated for epilepsy surgery: 42 underwent unilateral temporal lobe resections (25 left, 17 right, mean age at surgery 13.8 years), 11 were treated only pharmacologically. Average follow-up was 9 years (range 5-15). Post-surgical change in visual and verbal episodic memory, and semantic memory at follow-up were examined. Pre- and post-surgical T1-weighted MRI brain scans were analysed to extract hippocampal and resection volumes, and evaluate post-surgical temporal lobe integrity. Language lateralization indices were derived from functional magnetic resonance imaging. There were no significant pre- to postoperative decrements in memory associated with surgery. In contrast, gains in verbal episodic memory were seen after right temporal lobe surgery, and visual episodic memory improved after left temporal lobe surgery, indicating a functional release in the unoperated temporal lobe after seizure reduction or cessation. Pre- to post-surgical change in memory function was not associated with any indices of brain structure derived from MRI. However, better verbal memory at follow-up was linked to greater post-surgical residual hippocampal volumes, most robustly in left surgical participants. Better semantic memory at follow-up was associated with smaller resection volumes and greater temporal pole integrity after left temporal surgery. Results were independent of post-surgical intellectual function and language lateralization. Our findings indicate post-surgical, hemisphere-dependent material-specific improvement in memory functions in the intact temporal lobe. However, outcome was linked to the anatomical integrity of the temporal lobe memory system, indicating that compensatory mechanisms are constrained by the amount of tissue which remains in the operated temporal lobe. Careful tailoring of resections for children undergoing epilepsy surgery may enhance long-term memory outcome.

Simple Smell Test May Predict Donepezil Response

Simple Smell Test May Predict Donepezil Response

The effect of exercise on hippocampal volume and neurotrophines in patients with major depression–A randomized clinical trial

BackgroundThe hippocampal volume is reduced in patients with major depression. Exercise leads to an increased hippocampal volume in schizophrenia and in healthy old adults. The effect of exercise on hippocampal volume is potentially mediated by brain derived neurotrophic factor (BDNF), vascular endothelial growth factor (VEGF), and insulin like growth factor 1 (IGF-1). The aim of this trial was to assess the effect of an aerobic exercise intervention on hippocampal volume and serum BDNF, VEGF, and IGF-1 in patients with major depression. MethodsPatients were randomized to an aerobic exercise intervention (n=41) or a control condition (n=38). Both interventions consisted of three supervised sessions per week during a three months period. ResultsPost-intervention the increase in maximal oxygen uptake was 3.90ml/kg/min (SD 5.1) in the aerobic exercise group and 0.95ml/kg/min (SD 6.2) in the control group (p=0.03). The hippocampal volume, BDNF, VEGF, or IGF-1 did not differ between the two groups. Post-hoc we found a positive association between change in hippocampal volume and verbal memory (Rho=0.27; p=0.05) and change in hippocampal volume and depressive symptoms (Rho=0.30; p=0.03). LimitationsParticipation was low in both groups corresponding to an average participation of one session per week. ConclusionDespite a significant increase in maximal oxygen uptake, a pragmatic exercise intervention did not increase hippocampal volume or resting levels of neurotrophines in out-patients with mild to moderate major depression. Trial identifier: ClinicalTrials.gov (NCT00695552)

Effects of milnacipran on neurocognition, pain, and fatigue in fibromyalgia: a 13-week, randomized, placebo-controlled, crossover trial.

To investigate whether milnacipran is safe and effective in improving cognitive function in patients with fibromyalgia. Patients were randomly assigned to receive milnacipran or placebo for 6 weeks, followed by a 1-week washout and then crossover to the other arm for another 6 weeks. The overall trial lasted 13 weeks and was conducted between July 2011 and May 2013. Assessments were performed at each visit. Neurocognition was measured by the Brief Assessment of Cognition (BAC) and MATRICS. Pain was assessed by the visual analog scale (VAS) for pain. Global assessment of fibromyalgia symptoms was measured by the Fibromyalgia Impact Questionnaire (FIQ) and tender point examination. Depression was assessed by the Beck Depression Inventory (BDI). Fatigue was assessed by the Fatigue Severity Scale. Functional outcome was evaluated by the Health Assessment Questionnaire. The Clinical Global Impressions-Severity of Illness (CGI-S) and Improvement (CGI-I) scales and the Patients Clinical Global Impression of Change were used to measure the global impression of severity and improvement. 26 subjects were screened, and 20 subjects completed the trial. The change in verbal memory (P = .001) and the composite T score (P = .044) of the BAC and the change in the attention-vigilance domain T score (P = .042) were significantly improved, but there were no differences between the drug and placebo groups. The changes in the CGI-S scores were not significant, but the changes in the Clinical Impression-Improvement (CGI-I) scores showed worsening in the placebo group at week 1 (P = .032), week 2 (P = .024), week 4 (P = .024), and week 6 (P = .60) compared to baseline. The change in FIQ scores was not significant. Milnacipran may have a potential role in the improvement of pain, disability, and mood. The effect of milnacipran on cognition in fibromyalgia needs further research. ClinicalTrials.gov identifier: NCT01829243.

1913 – Longitudinal change in verbal learning and memory in schizophrenia and controls: A nine-year study in the Northern Finland Birth Cohort 1966

Patients with schizophrenia generally perform worse than control subjects on all cognitive domains, and particularly in memory functions. It is still unclear, how cognition changes during years of illness in schizophrenia. Our aim was to analyze the change in verbal learning and memory functions in subjects with schizophrenia and healthy controls during a 9-year follow-up. The sample was the general population based Northern Finland 1966 Birth Cohort. In 1999-2001 and in 2008-2010 field studies were performed, including repeated measures of clinical status and the California Verbal Learning Test (CVLT). CVLT was used for the estimation of the course of a possible change of verbal learning and memory during the follow-up. The sample included 41 individuals with schizophrenic psychoses and 74 non-psychotic controls. Both cases and controls had statistically significant decline in measures of CVLT. However, the change in verbal learning and memory in the 9 -year follow-up was not statistically significantly different between cases and controls. Among cases, age of illness onset and sex had no statistically significant effect on change of verbal learning and memory. According to our unselected, population based sample with long follow up, the impairments during the life span in verbal learning and memory in schizophrenia was not different compared to controls. These results imply that schizophrenia is not a progressing degenerative illness.

2082 – Lifetime use of antipsychotic medication and change of verbal learning and memory in schizophrenia in 9-years follow-up in general population sample

Cognitive deficits, such as verbal memory dysfunction, are a core feature of schizophrenia. Yet the longitudinal course and associations of cognitive deficits with antipsychotic medication remain unclear. Our aim was to analyze how lifetime antipsychotic dosage associates with the change of verbal learning and memory in individuals with schizophrenia during a 9-year follow-up. Forty-two subjects with schizophrenic psychoses (22 males) from the Northern Finland 1966 Birth Cohort went through diagnostic interviews and cognitive assessment including California Verbal Learning Test (CVLT) at the ages of 34 and 43 years. Data of the subjects’ lifetime antipsychotic doses in chlorpromazine equivalents were collected from patient history records, interviews and national registers. The association between verbal learning and memory (immediate free recall of trials 1-5 and free recall after long delay) and dose-years of antipsychotics was analyzed by logistic regression model. Higher dose-years of any and typical antipsychotics, but not atypical antipsychotics, associated statistically significantly to worse verbal learning and memory in cross-sectional analyses at age 34 years, even when onset age, sex, and severity of symptoms were controlled for. However, there was no statistically significant association between lifetime antipsychotic use and verbal learning and memory change between ages 34 and 43 years. High lifetime antipsychotic dose did not associate to decrease in verbal learning and memory in schizophrenia in 9 years of follow-up. To our knowledge, this is a first report on association between cumulative lifetime antipsychotic use and change in cognition in a long-term naturalistic follow-up.

Plasma omega-3 PUFA and white matter mediated executive decline in older adults

Introduction: Cross-sectional studies have identified long chain omega-3 polyunsaturated fatty acids (eicosapentaenoic acid 20:5n-3 and docosahexaenoic acid 22:6n-3 (O3PUFA) in association with fewer white matter lesions and better executive function in older adults. We hypothesized that O3PUFA are associated with less executive decline over time and that total white matter hyperintensity volume (WMH) mediates this association.Methods: Eighty-six non-demented older adults were followed over 4 years after measurement of plasma O3PUFA with annual evaluations of cognitive function. A subset of these participants also had brain MRI of total WMH available to conduct a formal mediation analysis of a putative relationship between O3PUFA and cognitive function.Results: Mean age at baseline was 86, 62% were female and 11% carried the APOE4 allele. Each 100 μg/ml increase in plasma O3PUFA associated with 4 s less change in executive decline per year of aging (p = 0.02, fully adjusted model). O3PUFA was not associated with verbal memory or global cognitive changes. The significance of the association between O3PUFA and better executive function was lost once WMH was added to the regression model.Conclusion: Executive decline with age appears to be a cognitive domain particularly sensitive to plasma O3PUFA in longitudinal examination. O3PUFA may modulate executive functioning by mechanisms underlying the development of WMH, a biologically plausible hypothesis that warrants further investigation.

Verbal memory decline is less frequent at 10 years than at 2 years after temporal lobe surgery for epilepsy

We investigated individual short- and long-term verbal memory changes after temporal lobe resection for epilepsy. Fifty-one patients (23 operated on the speech-dominant temporal lobe, DTL and 28 on the non-dominant temporal lobe, NDTL) were tested on learning/immediate recall and delayed recall of word-list and word-pairs preoperatively, 2years postoperatively and 10years postoperatively. Changes were defined using reliable change indices of 23 healthy controls assessed at corresponding intervals. Fewer patients had reliable declines at 10years than at 2years (DTL: 13–35% vs 35–44%; NDTL: 0–4% vs 7–21%). Four DTL patients (17%) had reliable declines in ≥2 tests at 10-year follow-up. More NDTL patients had improvement at 10years than at 2years (18–30% vs 4–22%). The only risk factor for decline both short and long term was DTL resection. In conclusion, most patients had stable verbal memory postoperatively. A few DTL patients had a lasting decline at long-term follow-up, but more patients showed partial recovery, especially in the NDTL group.

Dietary fat types and 4-year cognitive change in community-dwelling older women.

A study was undertaken to relate dietary fat types to cognitive change in healthy community-based elders. Among 6,183 older participants in the Women's Health Study, we related intake of major fatty acids (saturated [SFA], monounsaturated [MUFA], total polyunsaturated [PUFA], trans-unsaturated) to late-life cognitive trajectory. Serial cognitive testing, conducted over 4 years, began 5 years after dietary assessment. Primary outcomes were global cognition (averaging tests of general cognition, verbal memory, and semantic fluency) and verbal memory (averaging tests of recall). We used analyses of response profiles and logistic regression to estimate multivariate-adjusted differences in cognitive trajectory and risk of worst cognitive change (worst 10%) by fat intake. Higher SFA intake was associated with worse global cognitive (p for linear trend = 0.008) and verbal memory (p for linear trend = 0.01) trajectories. There was a higher risk of worst cognitive change, comparing highest versus lowest SFA quintiles; the multivariate-adjusted odds ratio (OR) with 95% confidence interval (CI) was 1.64 (1.04-2.58) for global cognition and 1.65 (1.04-2.61) for verbal memory. By contrast, higher MUFA intake was related to better global cognitive (p for linear trend < 0.001) and verbal memory (p for linear trend = 0.009) trajectories, and lower OR (95% CI) of worst cognitive change in global cognition (0.52 [0.31-0.88]) and verbal memory (0.56 [0.34-0.94]). Total fat, PUFA, and trans-fat intakes were not associated with cognitive trajectory. Higher SFA intake was associated with worse global cognitive and verbal memory trajectories, whereas higher MUFA intake was related to better trajectories. Thus, different consumption levels of the major specific fat types, rather than total fat intake itself, appeared to influence cognitive aging.

Working memory capacity correlates with implicit serial reaction time task performance

We recently reported that visuospatial working memory capacity predicts the rate of explicit motor sequence learning (Bo and Seidler in J Neurophysiol 101:3116-3125, 2009). In the current study, we evaluated relationships between visuospatial and verbal working memory and implicit performance change in the serial reaction time (SRT) task. Participants performed two computerized working memory tasks adapted from change detection working memory assessments, an implicit SRT task, and several neuropsychological tests. We observed significant correlations between visuospatial working memory (VSWM) and verbal working memory (VWM) performance. VSWM, VWM, and card rotation task were each significantly correlated with the rate of reaction time improvement in the SRT task. Multiple linear regression analysis revealed that VSWM explained a significant portion of the variance in rate of SRT performance change (exponential fit to the performance curve) across individual participants, and the addition of VWM did not significantly improve the model. These findings suggest that VSWM plays a role in the implicit performance improvement of second-order conditional sequences.

Presurgical language fMRI activation correlates with postsurgical verbal memory decline in left-sided temporal lobe epilepsy

We analysed the association of presurgical language fMRI activations and postsurgical verbal memory changes in 16 left-sided mesial temporal lobe epilepsy patients with initially intact memory. Patients with severe verbal memory decline after surgery (n = 9) had stronger presurgical fMRI activations within the left posterior temporal lobe, compared to those with no decline (n = 7). Language fMRI activation may predict verbal memory outcome, even in patients with a high risk of postsurgical memory deterioration.

Functional MRI is a valid noninvasive alternative to Wada testing

Partial removal of the anterior temporal lobe (ATL) is a highly effective surgical treatment for intractable temporal lobe epilepsy, yet roughly half of patients who undergo left ATL resection show a decline in language or verbal memory function postoperatively. Two recent studies demonstrate that preoperative fMRI can predict postoperative naming and verbal memory changes in such patients. Most importantly, fMRI significantly improves the accuracy of prediction relative to other noninvasive measures used alone. Addition of language and memory lateralization data from the intracarotid amobarbital (Wada) test did not improve prediction accuracy in these studies. Thus, fMRI provides patients and practitioners with a safe, noninvasive, and well-validated tool for making better-informed decisions regarding elective surgery based on a quantitative assessment of cognitive risk.

Heterogeneity of cognitive trajectories in diverse older persons.

This study examined trajectories of cognitive change in psychometrically matched measures of episodic memory, semantic memory, and executive function in an ethnically, demographically, and cognitively diverse sample of older persons. Individual rates of change showed considerable heterogeneity in each domain. Baseline clinical diagnosis predicted differential change in semantic memory and executive function, dementia > mild cognitive impairment (MCI) > normal, but average decline in verbal episodic memory was similar across all 3 diagnostic groups. There was substantial overlap of distributions of cognitive change across baseline diagnostic groups for all 3 measures. Cognitive change was strongly related to change in clinical diagnosis. Rapid and similar change was present for all 3 cognitive measures in patients with dementia and in those with normal cognition and those with MCI who progressed clinically. In cognitively normal patients, verbal episodic memory change was greater than change in the other two domains. Global status, measured by the Clinical Dementia Rating scale (Morris, 1993), predicted change in semantic memory and executive function, whereas APOE genotype predicted change in verbal episodic memory, and age had no effect on rates of change in any domain independent of global status and APOE. Results show important limitations in using cross-sectional diagnosis to predict prognosis and suggest that research to identify robust predictors of cognitive change across the full spectrum from normal to dementia is needed for better early identification of diseases that cause progressive decline.

A comparison of two fMRI methods for predicting verbal memory decline after left temporal lobectomy: Language lateralization versus hippocampal activation asymmetry

Language lateralization measured by preoperative functional magnetic resonance imaging (fMRI) was shown recently to be predictive of verbal memory outcome in patients undergoing left anterior temporal lobe (L-ATL) resection. The aim of this study was to determine whether language lateralization or functional lateralization in the hippocampus is a better predictor of outcome in this setting. Thirty L-ATL patients underwent preoperative language fMRI, preoperative hippocampal fMRI using a scene encoding task, and pre- and postoperative neuropsychological testing. A group of 37 right ATL (R-ATL) surgery patients was included for comparison. Verbal memory decline occurred in roughly half of the L-ATL patients. Preoperative language lateralization was correlated with postoperative verbal memory change. Hippocampal activation asymmetry was strongly related to side of seizure focus and to Wada memory asymmetry but was unrelated to verbal memory outcome. Preoperative hippocampal activation asymmetry elicited by a scene encoding task is not predictive of verbal memory outcome. Risk of verbal memory decline is likely to be related to lateralization of material-specific verbal memory networks, which are more closely correlated with language lateralization than with overall asymmetry of episodic memory processes.

Effects of botanicals and combined hormone therapy on cognition in postmenopausal women.

The aim of this study was to characterize the effects of red clover, black cohosh, and combined hormone therapy on cognitive function in comparison to placebo in women with moderate to severe vasomotor symptoms. In a phase II randomized, double-blind, placebo-controlled study, 66 midlife women (of 89 from a parent study; mean age, 53 y) with 35 or more weekly hot flashes were randomized to receive red clover (120 mg), black cohosh (128 mg), 0.625 mg conjugated equine estrogens plus 2.5 mg medroxyprogesterone acetate (CEE/MPA), or placebo. Participants completed measures of verbal memory (primary outcome) and other cognitive measures (secondary outcomes) before and during the 12th treatment month. A subset of 19 women completed objective, physiological measures of hot flashes using ambulatory skin conductance monitors. Neither of the botanical treatments had an impact on any cognitive measure. Compared with placebo, CEE/MPA led to a greater decline in verbal learning (one of five verbal memory measures). This effect just missed statistical significance (P = 0.057) in unadjusted analyses but reached significance (P = 0.02) after adjusting for vasomotor symptoms. Neither of the botanical treatment groups showed a change in verbal memory that differed from the placebo group (Ps > 0.28), even after controlling for improvements in hot flashes. In secondary outcomes, CEE/MPA led to a decrease in immediate digit recall and an improvement in letter fluency. Only CEE/MPA significantly reduced objective hot flashes. Results indicate that a red clover (phytoestrogen) supplement or black cohosh has no effects on cognitive function. CEE/MPA reduces objective hot flashes but worsens some aspects of verbal memory.

The intracarotid amobarbital or Wada test: unilateral or bilateral?

In the Netherlands, presurgical screening for temporal lobe epilepsy (TLE) includes the intracarotid amobarbital procedure (IAP), consisting of two consecutive injections of amobarbital, ipsilateral and contralateral to the epileptic focus. We studied whether a bilateral IAP has added value to a unilateral, ipsilateral IAP. This population-based study included 183 consecutive patients referred for screening for TLE surgery who underwent bilateral IAP. Using multivariable modeling, we assessed the added value of bilateral IAP on the decision for surgery, resection size, amygdalohippocampectomy, post-operative seizure freedom, memory performance, and IQ change. Given the results from the unilateral IAP, the bilateral IAP had added prognostic value for postoperative change in verbal memory (P < 0.01) and verbal IQ (P < 0.01), especially if patients had a left-sided focus. In contrast, information provided by the contralateral IAP was not associated with decision-making or surgical strategy. A bilateral IAP has added value in predicting post-operative verbal memory and IQ. A bilateral IAP is currently not used to guide surgical strategy, but may be used for this purpose when verbal capacity is of particular concern in patients with a left-sided focus. In other cases, IAP is best performed unilaterally.

Effects of menstrual cycle phase and oral contraceptive use on verbal memory

Surgical or pharmacological suppression of ovarian hormones leads to declines in verbal memory, and estrogen treatment reverses these deficits. In the current study, we investigated the effects of menstrual cycle phase and oral contraceptives on verbal memory, as measured by the California Verbal Learning Test, in two groups of premenopausal women — 16 naturally cycling women and 20 current users of estrogen-based oral contraceptives (OCs). Naturally cycling women were assessed twice — once during the early follicular phase (Days 2–4) and once during the midluteal phase (Days 20–22) of the menstrual cycle. OC users were tested on the same cycle days, corresponding to inactive and active pill phases, respectively. We predicted that naturally cycling women would show improved verbal memory during the midluteal phase, when estradiol levels are high, compared with the follicular phase, when estradiol levels are low. We also predicted that OC users, who show no change in endogenous estradiol across the cycle, would show no change in verbal memory. Contrary to predictions, naturally cycling women showed no changes in verbal memory across the cycle, whereas OC users showed enhanced memory during the active pill phase ( p < .05). None of the secondary cognitive outcome measures varied with cycle phase or OC use including measures of visuospatial memory, verbal fluency, visuospatial abilities, and attention. Overall, these results suggest that verbal memory performance in premenopausal women varies across the cycle with OC use, but does not vary systematically with changes in endogenous estradiol.

Verbal cognition and attention deficits do not explain the verbal memory decline associated with pharmacoresistant partial epilepsy

The aim of this study was to explore whether change in verbal memory with time in patients with epilepsy is influenced by performance on tasks assessing verbal cognition or attention/processing speed. Thirty-six patients and twenty-five healthy controls were tested twice with median retest intervals of 4.8 and 3.1 years, respectively. Aspects of verbal memory, verbal cognition, and attention/processing speed were assessed. Decline in one verbal memory variable (Cronholm–Molander Memory Test Paired Associates—Delayed Recall) was the strongest correlate of epilepsy. The second strongest correlate was a decrease in one attention/processing speed variable (Digit Symbol). The relationship between decline in verbal memory and epilepsy was not influenced by the decline in attention/processing speed, and the results did not support the notion that limited mental reserves as reflected in impaired verbal cognition or attention/processing speed can explain the relationship between verbal memory and epilepsy.

Characterization of verbal and spatial memory changes from moderate to supraphysiological increases in serum testosterone in healthy older men

It has been suggested that cognitive changes in response to T supplementation may occur within an ideal range. The objective of this study was to compare the cognitive responses of older, eugonadal men in whom moderate or large increases in serum testosterone levels was induced by exogenous testosterone supplementation. Randomized, double-blind, placebo-controlled study with subsequent grouping of participants according to average increase in circulating T from baseline. Community dwelling participants. Fifty-seven healthy, eugonadal, community dwelling male volunteers, mean age 67 years (+/-11 years). Participants were randomized to receive weekly intramuscular (i.m.) injections of either 50, 100 or 300 mg T enanthate or placebo (saline) injection for 6 weeks. Cognitive evaluations using a battery of neuropsychological tests were conducted at baseline, weeks 3 and 6 of treatment and after 6 weeks of wash-out. Performance on cognitive tests of verbal and spatial memory. Men with moderate increases in serum T and/or its metabolites demonstrated significant improvements in verbal and spatial memory. In contrast, men with large or low increases in circulating T levels, failed to demonstrate significant changes in memory. These results suggest that in healthy older men, beneficial changes in cognitive function induced by T supplementation are most evident with moderate changes in cognition from moderate to high T supplementation increases in T levels. Large or no to low increases in T levels do not appear to appreciably effect cognition.