Verbal Memory Deficits in OEF/OIF/OND Veterans Exposed to Blasts at Close Range.

OBJECTIVES: This study investigated the relationship between close proximity to detonated blast munitions and cognitive functioning in OEF/OIF/OND Veterans. METHODS: A total of 333 participants completed a comprehensive evaluation that included assessment of neuropsychological functions, psychiatric diagnoses and history of military and non-military brain injury. Participants were assigned to a Close-Range Blast Exposure (CBE) or Non-Close-Range Blast Exposure (nonCBE) group based on whether they had reported being exposed to at least one blast within 10 meters. RESULTS: Groups were compared on principal component scores representing the domains of memory, verbal fluency, and complex attention (empirically derived from a battery of standardized cognitive tests), after adjusting for age, education, PTSD diagnosis, sleep quality, substance abuse disorder, and pain. The CBE group showed poorer performance on the memory component. Rates of clinical impairment were significantly higher in the CBE group on select CVLT-II indices. Exploratory analyses examined the effects of concussion and multiple blasts on test performance and revealed that number of lifetime concussions did not contribute to memory performance. However, accumulating blast exposures at distances greater than 10 meters did contribute to poorer performance. CONCLUSIONS: Close proximity to detonated blast munitions may impact memory, and Veterans exposed to close-range blast are more likely to demonstrate clinically meaningful deficits. These findings were observed after statistically adjusting for comorbid factors. Results suggest that proximity to blast should be considered when assessing for memory deficits in returning Veterans. Comorbid psychiatric factors may not entirely account for cognitive difficulties. (JINS, 2018, 24, 466-475).

Health Outcomes of Obtaining Housing Among Older Homeless Adults.

OBJECTIVES: We determined the impact of obtaining housing on geriatric conditions and acute care utilization among older homeless adults. METHODS: We conducted a 12-month prospective cohort study of 250 older homeless adults recruited from shelters in Boston, Massachusetts, between January and June 2010. We determined housing status at follow-up, determined number of emergency department visits and hospitalizations over 12 months, and examined 4 measures of geriatric conditions at baseline and 12 months. Using multivariable regression models, we evaluated the association between obtaining housing and our outcomes of interest. RESULTS: At 12-month follow-up, 41% of participants had obtained housing. Compared with participants who remained homeless, those with housing had fewer depressive symptoms. Other measures of health status did not differ by housing status. Participants who obtained housing had a lower rate of acute care use, with an adjusted annualized rate of acute care visits of 2.5 per year among participants who obtained housing and 5.3 per year among participants who remained homeless. CONCLUSIONS: Older homeless adults who obtained housing experienced improved depressive symptoms and reduced acute care utilization compared with those who remained homeless.

Decreased white matter integrity in neuropsychologically defined mild cognitive impairment is independent of cortical thinning.

Improved understanding of the pattern of white matter changes in early and prodromal Alzheimer's disease (AD) states such as mild cognitive impairment (MCI) is necessary to support earlier preclinical detection of AD, and debate remains whether white matter changes in MCI are secondary to gray matter changes. We applied neuropsychologically based MCI criteria to a sample of normally aging older adults; 32 participants met criteria for MCI and 81 participants were classified as normal control (NC) subjects. Whole-head high resolution T1 and diffusion tensor imaging scans were completed. Tract-Based Spatial Statistics was applied and a priori selected regions of interest were extracted. Hippocampal volume and cortical thickness averaged across regions with known vulnerability to AD were derived. Controlling for corticalthic kness, the MCI group showed decreased average fractional anisotropy (FA) and decreased FA in parietal white matter and in white matter underlying the entorhinal and posterior cingulate cortices relative to the NC group. Statistically controlling for cortical thickness, medial temporal FA was related to memory and parietal FA was related to executive functioning. These results provide further support for the potential role of white matter integrity as an early biomarker for individuals at risk for AD and highlight that changes in white matter may be independent of gray matter changes.

Detecting cognitive impairment in individuals at risk for cardiovascular disease: the "Clock-in-the-Box" screening test.

OBJECTIVE: The purpose of this study was to evaluate the performance on the Clock-in-the-Box (CIB), a screening measure for cognitive function, relative to neuropsychological testing in an older population with cardiovascular risk. METHODS: A prospective cohort of older patients (>50 years) with cardiovascular risk was recruited to perform the CIB and complete a brief neuropsychological battery consisting of Trailmaking tests, the Hopkins Verbal Learning Test (HVLT), and fluency tasks. Performance on the CIB was scored according to standard criteria (range 0-8, 0-worst). The performance on the total CIB, working memory subscale (CIB-WM), and planning/organization (COB-PO) was compared to neuropsychological measures. RESULTS: The cohort (n = 127) was older (age 67 ± 7 years) and diverse with 33% female (n = 42) and 42% non-white race (n = 53). Cardiac risk factors were prevalent: hypertension (83%), hyperlipidemia (74%), overweight (84%), diabetes (48%), prior cardiac disease (39%), and smoking (11%). The CIB (mean 6.5 ± 1.3) took 84 ± 21 s on average to complete and had good inter-rater reliability (κ = 0.809, p < 0.01). The CIB-WM subscale was significantly correlated with performance on Trailmaking B and HVLT learning, recall, and recognition. The CIB-PO subscale was significantly associated with semantic and phonemic fluency, Trailmaking B, and HVLT learning and recall. In regression modeling, CIB-WM significantly predicted performance on HVLT learning, recall, and retention. CIB-PO subscale predicted performance on Trailmaking B, HVLT learning, and HVLT recall. CONCLUSIONS: The CIB is a brief cognitive screening instrument with good reliability and predictive validity in a CV risk population. The CIB-WM and CIB-PO subscales could provide utility for clinicians.

Hippocampal volume and declarative memory function in combat-related PTSD.

The proposition that declarative memory deficits are systematically related to smaller hippocampal volume was tested in a relatively large sample (n = 95) of U.S. military veterans with and without combat-related posttraumatic stress disorder. This correlative analysis was extended by including multiple measures of verbal and visual declarative memory and multiple memory-relevant regional brain volumes that had been shown to exhibit main effects of PTSD in prior work. Small-to-moderate effects were observed on verbal declarative memory in line with a recent meta-analysis; nevertheless, little or no evidence of systematic linear covariation between memory measures and brain volumes was observed.

Using lexical familiarity judgments to assess verbally mediated intelligence in aphasia.

In this study, a task using forced-choice lexical familiarity judgments of irregular versus archaic words (a newly developed measure called the Lexical Orthographic Familiarity Test; LOFT) was compared to a standardized oral word-reading measure (the Wechsler Test of Adult Reading; WTAR) in a group of 35 aphasic adults and a comparison group of 125 community dwelling, nonbrain damaged adults. When compared to the comparison group, aphasics had significantly lower scores on the WTAR but not the LOFT. Although both the WTAR and LOFT were significantly correlated with education in the nonbrain-damaged group, only the LOFT was correlated with education and also with the Barona full scale IQ index in the aphasic group. Lastly, WTAR performance showed a significantly greater relationship to the severity of language disorder in the aphasic group than did the LOFT. These results have both theoretical and clinical implications for the assessment of language-disordered adults, as they indicate that patients with aphasia may retain aspects of verbally mediated intelligence, and that the LOFT may provide a better estimate of premorbid functioning in aphasia than other currently available measures.

Prevalence of Cognitive Impairment and Association With Survival Among Older Patients With Hematologic Cancers.

Importance: As the population ages, cognitive impairment has promised to become increasingly common among patients with cancer. Little is known about how specific domains of cognitive impairment may be associated with survival among older patients with hematologic cancers. Objective: To determine the prevalence of domain-specific cognitive impairment and its association with overall survival among older patients with blood cancer. Design, Setting, and Participants: This prospective observational cohort study included all patients 75 years and older who presented for initial consultation in the leukemia, myeloma, or lymphoma clinics of a large tertiary hospital in Boston, Massachusetts, from February 1, 2015, to March 31, 2017. Patients underwent screening for frailty and cognitive dysfunction and were followed up for survival. Exposures: The Clock-in-the-Box (CIB) test was used to screen for executive dysfunction. A 5-word delayed recall test was used to screen for impairment in working memory. The Fried frailty phenotype and Rockwood cumulative deficit model of frailty were also assessed to characterize participants as robust, prefrail, or frail. Results: Among 420 consecutive patients approached, 360 (85.7%) agreed to undergo frailty assessment (232 men [64.4%] and 128 women [35.6%]; mean [SD] age, 79.8 [3.9] years), and 341 of those (94.7%) completed both cognitive screening tests. One hundred twenty-seven patients (35.3%) had probable executive dysfunction on the CIB, and 62 (17.2%) had probable impairment in working memory on the 5-word delayed recall. Impairment in either domain was modestly correlated with the Fried frailty phenotype (CIB, ρ = 0.177; delayed recall, ρ = 0.170; P = .01 for both), and many phenotypically robust patients also had probable cognitive impairment (24 of 104 [23.1%] on CIB and 9 of 104 [8.7%] on delayed recall). Patients with impaired working memory had worse median survival (10.9 [SD, 12.9] vs 12.2 [SD, 14.7] months; log-rank P < .001), including when stratified by indolent cancer (log-rank P = .01) and aggressive cancer (P < .001) and in multivariate analysis when adjusting for age, comorbidities, and disease aggressiveness (odds ratio, 0.26; 95% CI, 0.13-0.50). Impaired working memory was also associated with worse survival for those undergoing intensive treatment (log-rank P < .001). Executive dysfunction was associated with worse survival only among patients who underwent intensive treatment (log-rank P = .03). Conclusions and Relevance: These data suggest that domains of cognitive dysfunction may be prevalent in older patients with blood cancer and may have differential predictive value for survival. Targeted interventions are needed for this vulnerable patient population.

Elevated rates of memory impairment in military service-members and veterans with posttraumatic stress disorder.

INTRODUCTION: Studies investigating the neurocognitive effects of posttraumatic stress disorder (PTSD) routinely find "deficits" in various cognitive domains. However, the rate of cognitive impairment in individuals with PTSD remains unclear, as studies have focused on null hypothesis testing (NHT) and inferring patterns of impairment rather than empirically determining the rate of cognitive impairment in this sample. METHOD: This study examined rates of cognitive impairment using a domain-specific approach in non-treatment-seeking Operation Enduring Freedom/Operation Iraqi Freedom/Operation New Dawn service members and veterans with (n = 92) and without (n = 79) PTSD and without substance abuse/dependence who passed a performance validity measure and were matched on age, education, estimated IQ, and ethnicity. Chi-square analyses were used to compare the rate of cognitive impairment across groups based on normative scores using three cutoffs (-1, -1.5, and -2 SDs). NHT was also used to compare performances across groups. RESULTS: Individuals with PTSD showed higher rates of impairment in memory (-1-SD cutoff) than controls, but equivalent rates of impairment in attention, processing speed, and executive functioning; no significant differences were found on NHT. Impairment in any domain was also more prevalent in PTSD (-1-, -1.5-, and -2-SD cutoffs). No differences were found on NHT or rates of impairment in individuals with PTSD with (n = 34) and without (n = 58) depression. CONCLUSIONS: Patients with PTSD were more likely to meet criteria for memory impairment and to show impairment in any domain than controls. Patients with PTSD and comorbid depression were no more likely to be impaired in any cognitive domain or to have lower scores on individual cognitive tasks than patients with PTSD alone. Clinicians noting cognitive impairment in individuals with PTSD should exercise caution before ascribing that impairment to another etiology if deficits are limited to memory.

Impaired executive function is associated with delirium after coronary artery bypass graft surgery.

OBJECTIVES: To determine the extent to which preoperative performance on tests of executive function and memory was associated with delirium after coronary artery bypass graft (CABG) surgery. DESIGN: Prospective observational cohort study. SETTING: Two academic medical centers and one Department of Veterans Affairs medical center in Massachusetts. PARTICIPANTS: Eighty subjects without preoperative delirium undergoing CABG or CABG-valve surgery completed baseline neuropsychological assessments with validated measures of memory and executive function. MEASUREMENTS: Beginning on postoperative Day 2, a battery to diagnose delirium was administered daily. Confirmatory factor analysis (CFA) was used to define two cognitive domain composites (memory and executive function). The loading pattern of neuropsychological measures onto the latent cognitive domains was determined a priori. Poisson regression was used to model the association between neuropsychological performance and cognitive domain composite scores and risk of postoperative delirium. The association was expressed as the difference between impaired (0.5 standard deviations (SDs) below mean) and nonimpaired (0.5 SDs above mean) performers. RESULTS: Forty subjects (50%) developed delirium. Measures of memory function were not significantly related to delirium. Of the executive function measures, verbal fluency, category fluency, Hopkins Verbal Learning Test learning, and backward recounting of days and months were significantly related to delirium. Preoperative mental status was a strong predictor of postoperative delirium. After controlling for age, sex, education, medical comorbidity, mental status, and the other cognitive domain, CFA cognitive domain composites suggest that risk for delirium is specific for executive functioning impairment (relative risk (RR) = 2.77, 95% confidence interval (CI) = 1.12-6.87) but not for memory impairment (RR = 0.49, 95% CI = 0.19-1.25). CONCLUSION: Worse preoperative performance in executive function was independently associated with greater risk of developing delirium after CABG.

Visual selective attention in Parkinson's disease: dissociation of exogenous and endogenous inhibition.

Impairment in the inhibitory mechanism of visual selective attention in patients with Parkinson's disease (PD) is controversial. The present study sought to understand disparate findings in a manner analogous to the relative preservation of exogenously evoked movement and impairment of endogenously evoked movement. The authors examined inhibition of return (i.e., exogenously evoked inhibition; IOR) and negative priming (i.e., endogenously evoked inhibition; NP) in a group of 14 patients with PD and 14 healthy controls (HC). Unlike the HC, who demonstrated significant inhibition in both tasks, the group with PD demonstrated intact inhibition only in the IOR task. Dopamine replacement therapy did not affect performance. The findings are discussed within the context of a model that differentiates the essential involvement of the basal ganglia for endogenously evoked spatial inhibition.

The Clock-in-the-Box, a brief cognitive screen, is associated with failure to return home in an elderly hospitalized sample.

PURPOSE: Cognitive screening upon hospital admission can provide important information about the patient's ability to process information during the inpatient stay. The Clock-in-the-Box (CIB) is a rapidly administered cognitive screening measure which has been previously validated with cognitive screening and neuropsychological assessments. The purpose of this study is to demonstrate the predictive validity of the CIB for discharge location among a sample of older medical inpatients. PATIENTS AND METHODS: Hospitalized Veterans (N=218), aged 55 years and older, were recruited on the day after admission after they gave their consent. These participants completed the CIB, the Montreal Cognitive Assessment, and self-report measures of daily functioning. Using logistic regression models, the bivariable and multivariable impact of the cognitive screening and functional assessments were examined for their ability to predict whether the participants did not return home after hospitalization (eg, admission to subacute rehabilitation facilities or nursing facilities). RESULTS: The participants were older (mean 71.5±9.5 years) and predominantly male (92.7%). The CIB score was independently associated with discharge to locations other than home (odds ratio =0.72, 95% confidence interval =0.60-0.87, P=0.001) and remained associated after adjusting for demographics, prehospitalization functional abilities, and Montreal Cognitive Assessment score (adjusted odds ratio =0.55, 95% confidence interval =0.36-0.83, P=0.004). CONCLUSION: The current evidence, combined with its brevity and ease of use, supports the use of the CIB as a cognitive screen for inpatient older adults, in order to help inform clinical treatment decisions and discharge planning.

Event-based prospective memory among veterans: The role of posttraumatic stress disorder symptom severity in executing intentions.

OBJECTIVE: Posttraumatic stress disorder (PTSD) has been linked with neuropsychological deficits in several areas, including attention, learning and memory, and cognitive inhibition. Although memory dysfunction is among the most commonly documented deficits associated with PTSD, our existing knowledge pertains only to retrospective memory. The current study investigated the relationship between PTSD symptom severity and event-based prospective memory (PM). METHOD: Forty veterans completed a computerized event-based PM task, a self-report measure of PTSD, and measures of retrospective memory. RESULTS: Hierarchical regression analysis results revealed that PTSD symptom severity accounted for 16% of the variance in PM performance, F(3, 36) = 3.47, p < .05, after controlling for age and retrospective memory. Additionally, each of the three PTSD symptom clusters was related, to varying degrees, with PM performance. CONCLUSIONS: Results suggest that elevated PTSD symptoms may be associated with more difficulties completing tasks requiring PM. Further examination of PM in PTSD is warranted, especially in regard to its impact on everyday functioning.

Glucose Dysregulation Interacts With APOE-∊4 to Potentiate Temporoparietal Cortical Thinning.

We examined the interactive effects of apolipoprotein ∊4 (APOE-∊4), a risk factor for Alzheimer's disease (AD), and diabetes risk on cortical thickness among 107 healthy elderly participants; in particular, participants included 27 APOE-∊4+ and 80 APOE-∊4- controls using T1-weighted structural magnetic resonance imaging. Regions of interests included select frontal, temporal, and parietal cortical regions. Among APOE-∊4, glucose abnormalities independently predicted reduced cortical thickness among temporoparietal regions but failed to predict changes for noncarriers. However, among noncarriers, age independently predicted reduced cortical thickness among temporoparietal and frontal regions. Diabetes risk is particularly important for the integrity of cortical gray matter in APOE-∊4 and demonstrates a pattern of thinning that is expected in preclinical AD. However, in the absence of this genetic factor, age confers risk for reduced cortical thickness among regions of expected compromise. This study supports aggressive management of cerebrovascular factors and earlier preclinical detection of AD among individuals presenting with genetic and metabolic risks.

Interactive effects of apolipoprotein E4 and diabetes risk on later myelinating white matter regions in neurologically healthy older aged adults.

Possession of the apolipoprotein E4 (APOE4) allele and diabetes risk are independently related to reduced white matter (WM) integrity that may contribute to the development of Alzheimer's disease (AD). The purpose of this study is to examine the interactive effects of APOE4 and diabetes risk on later myelinating WM regions among healthy elderly individuals at risk of AD. A sample of 107 healthy elderly (80 APOE4-/27 APOE4+) individuals underwent structural magnetic resonance imaging/diffusion tensor imaging (DTI). Data were prepared using Tract-Based Spatial Statistics, and a priori regions of interest (ROIs) were extracted from T1-based WM parcellations. Regions of interest included later myelinating frontal/temporal/parietal WM regions and control regions measured by fractional anisotropy (FA). There were no APOE group differences in DTI for any ROI. Within the APOE4 group, we found negative relationships between hemoglobin A1c/fasting glucose and APOE4 on FA for all later myelinating WM regions but not for early/middle myelinating control regions. Results also showed APOE4/diabetes risk interactions for WM underlying supramarginal, superior temporal, precuneus, superior parietal, and superior frontal regions. Results suggest interactive effects of APOE4 and diabetes risk on later myelinating WM regions, which supports preclinical detection of AD among this particularly susceptible subgroup.

Independent association between preoperative cognitive status and discharge location after cardiac surgery.

BACKGROUND: Among cardiac surgery patients, those with impaired cognitive status before surgery may have longer postoperative stays than do patients with normal status and may require additional care upon discharge. OBJECTIVES: To determine if preoperative scores on a screening measure for cognitive status (the Clock-in-the-Box), were associated with postoperative length of stay and discharge to a location other than home in patients who had cardiac surgery. METHODS: A total of 181 consecutive patients scheduled for cardiac surgery at a single site were administered the Clock-in-the-Box as part of the preoperative evaluation. Scores on the Clock-in-the-Box tool, demographic and operative information, postoperative length of stay, and discharge location were collected retrospectively from medical records. RESULTS: The mean age of the patients was 68.1 years (SD, 0.7), and 99% were men. Mean postoperative length of stay was 10.5 days (SD, 8.2), and 35 patients (19%) were discharged to a facility. Scores on the Clock-in-the-Box assessment were not associated with postoperative length of stay. Increasing age, living alone before surgery, and duration of cardiopulmonary bypass were associated with discharge to a facility and were used as covariates in adjusted analyses. After adjustment, better preoperative cognitive status reduced the risk of being discharged to a facility (adjusted relative risk, 0.93; 95% confidence interval, 0.89-0.98) after cardiac surgery. CONCLUSIONS: Cognitive screening before cardiac surgery can identify patients with impaired cognitive status who are less likely than patients with normal cognitive status to return home after cardiac surgery.

Cognitive screening in community-dwelling elders: performance on the clock-in-the-box.

BACKGROUND: The Clock-in-the-Box is a rapid (2-minute) cognitive screening tool. The purpose of this study was to compare the Clock-in-the-Box with the Mini-Mental State Exam and neuropsychologic tests; to determine Clock-in-the-Box score normative values by age and education group; and to determine if the Clock-in-the-Box score is associated with measures of physical function. METHODS: Community-dwelling older participants in the Boston area were recruited for a prospective, longitudinal study in which they completed a variety of cognitive and functional assessments. RESULTS: At baseline, participants (n=798; mean age [± standard deviation]=78.2 [±5.5] years; 14 [±3] mean years of education) completed in-home assessments of cognition (Clock-in-the-Box and Mini-Mental State Exam), measures of independent function (Activities of Daily Living and Instrumental Activities of Daily Living), and measures of physical function (Short Physical Performance Battery). The mean Mini-Mental State Exam score was 27.1 (±1.6; range 0-30 [0 worst]), and the mean Clock-in-the-Box score was 6.2 (±1.6; range 0-8 [0 worst]). Performance on the Clock-in-the-Box was correlated (Spearman) with the Mini-Mental State Exam (r=0.49, P<.001) and neuropsychologic measures (r=0.37-0.50; P<.001). Higher Clock-in-the-Box score was significantly associated with no difficulty in Activities of Daily Living (χ(2) = 39.6, P<.001) and Instrumental Activities of Daily Living (χ(2) = 35.5, P<.001). In addition, higher Clock-in-the-Box scores were associated with higher scores on the Short Physical Performance Battery (F=5.4, P<.001). CONCLUSION: The Clock-in-the-Box is a brief cognitive screening test that is correlated with the Mini-Mental State Exam, neuropsychologic tests, and measures of independent and physical function in community-dwelling older adults.

Variation in blood pressure is associated with white matter microstructure but not cognition in African Americans.

Although hypertension is a major risk factor for cerebrovascular disease (CVD) and is highly prevalent in African Americans, little is known about how blood pressure (BP) affects brain-behavior relationships in this population. In predominantly Caucasian populations, high BP is associated with alterations in frontal-subcortical white matter and in executive functioning aspects of cognition. We investigated associations among BP, brain structure, and neuropsychological functioning in 52 middle-older-age African Americans without diagnosed history of CVD. All participants underwent diffusion tensor imaging for examination of white matter integrity, indexed by fractional anisotropy (FA). Three regions of interest were derived in the anterior (genu) and posterior (splenium) corpus callosum and across the whole brain. A brief neuropsychological battery was administered from which composite scores of executive function and memory were derived. Blood pressure was characterized by mean arterial blood pressure (MABP). When controlling for age, higher MABP was associated with lower FA in the genu, and there was a trend for this same relationship with regard to whole-brain FA. When the sample was broken into groups on the basis of treatment for BP regulation (medicated vs. nonmedicated), MABP was related to genu and whole-brain FA only in the nonmedicated group. Neither MABP nor FA was significantly related to either neuropsychological composite score regardless of medication use. These data provide important evidence that variation in BP may contribute to significant alterations in specific neural regions of white matter in nonmedicated individuals without symptoms of overt CVD.

The effects of movement direction and hemispace on estimates of distance traveled.

BACKGROUND/HYPOTHESIS: The degree of attention directed to a stimulus and the presence of anisometric representations can alter the perception of the magnitude of a stimulus. We wanted to learn if normal right-handed subjects' estimates of distance traveled are influenced by the right-left direction or hemispace of movements. METHODS: We had blindfolded participants estimate the distance their arm was moved in a rightward or leftward direction, in right and left hemispace. Since we wanted subjects to estimate the distance traveled rather than compute the distance between the start and finish points, the subjects' arms were passively moved in sinusoidal trajectories at a constant speed. RESULTS: Subjects estimated leftward movements as longer than rightward movements, but there was no effect of hemispace. COMMENTS/CONCLUSIONS: People often attend more to novel than routine conditions and therefore participants might have overestimated the distance associated with leftward versus rightward movement because right-handed people more frequently move their right hand in a rightward direction and learn to read and write using rightward movements. Thus, leftward movements might be more novel and more attended than rightward movements and this enhanced directional attention might have influenced estimates of magnitude (distance).

Temporal lobe epilepsy as a model to understand human memory: the distinction between explicit and implicit memory.

Decades of research have provided substantial evidence of memory impairments in patients with temporal lobe epilepsy (TLE), including deficits in the encoding, storage, and retrieval of new information. These findings are not surprising, given the associated underlying neuroanatomy, including the hippocampus and surrounding medial temporal lobe structures. Because of its associated anatomic and cognitive characteristics, TLE has provided an excellent model by which to examine specific aspects of human memory functioning, including classic distinctions such as that between explicit and implicit memory. Various clinical and experimental research studies have supported the idea that both conscious and unconscious processes support memory functioning, but the role of relevant brain structures has been the subject of debate. This review is concerned with a discussion of the current status of this research and, importantly, how TLE can inform future studies of memory distinctions.