Verbal Episodic Learning Research Articles

Mid-life sleep is associated with cognitive performance later in life in aging American Indians: data from the Strong Heart Study.

Sleep-related disorders have been associated with cognitive decline and neurodegeneration. American Indians are at increased risk for dementia. Here, we aim to characterize, for the first time, the associations between sleep characteristics and subsequent cognitive performance in a sample of aging American Indians. We performed analyses on data collected in two ancillary studies from the Strong Heart Study, which occurred approximately 10 years apart with an overlapping sample of 160 American Indians (mean age at follow-up 73.1, standard deviation 5.6; 69.3% female and 80% with high school completion). Sleep measures were derived by polysomnography and self-reported questionnaires, including sleep timing and duration, sleep latency, sleep stages, indices of sleep-disordered breathing, and self-report assessments of poor sleep and daytime sleepiness. Cognitive assessment included measures of general cognition, processing speed, episodic verbal learning, short and long-delay recall, recognition, and phonemic fluency. We performed correlation analyses between sleep and cognitive measures. For correlated variables, we conducted separate linear regressions. We analyzed the degree to which cognitive impairment, defined as more than 1.5 standard deviations below the average Modified Mini Mental State Test score, is predicted by sleep characteristics. All regression analyses were adjusted for age, sex, years of education, body mass index, study site, depressive symptoms score, difference in age from baseline to follow-up, alcohol use, and presence of APOE e4 allele. We found that objective sleep characteristics measured by polysomnography, but not subjective sleep characteristics, were associated with cognitive performance approximately 10 years later. Longer sleep latency was associated with worse phonemic fluency (β = -0.069, p = 0.019) and increased likelihood of being classified in the cognitive impairment group later in life (odds ratio 1.037, p = 0.004). Longer duration with oxygen saturation < 90% was associated with better immediate verbal memory, and higher oxygen saturation with worse total learning, short and long-delay recall, and processing speed. In a sample of American Indians, sleep characteristics in midlife were correlated with cognitive performance a decade later. Sleep disorders may be modifiable risk factors for cognitive impairment and dementia later in life, and suitable candidates for interventions aimed at preventing neurodegenerative disease development and progression.

Measuring episodic verbal learning ability in alcohol-related cognitive disorders in relation to everyday functioning

Adequate and timely assessment of learning abilities in individuals with alcohol-related cognitive disorders is highly relevant to optimize addiction care. Learning curves of episodic verbal memory tests have been used to assess learning ability in various neurocognitive disorders, but studies in alcohol-related cognitive disorders are lacking. Therefore, this study investigated California Verbal Learning Test (CVLT) learning curves in individuals with alcohol-use disorder (AUD) with and without cognitive impairments and examined associations between learning curves and changes in everyday functioning following a multicomponent care program. We fitted learning curves over the five immediate recall trials of the Dutch version of the CVLT of patients with Korsakoff's syndrome (KS; N = 117), alcohol-related cognitive impairment no KS (ARCI; N = 147), and uncomplicated AUD (N = 43) using a generalized non-linear mixed regression. This model was based on three different parameters: initial memory performance (attention), maximum number of correctly recalled words (maximum learning), and the increase of correctly recalled words over the trials (learning rate). Next, we related these learning curves with ratings of everyday activities using the Patient Competency Rating Scale (PCRS) before and after a care program following admission. Modelled learning curves differed across groups, with significant differences in Attention (KS<ARCI<AUD, p < 0.001), Maximum Learning (KS<ARCI<AUD, p<0.001), and Learning Rate (KS<ARCI=AUD, p < 0.001). However, modelled learning curves were not related to reliable improvement in PCRS scores (p>0.05). Although modelled learning curves may be used to differentiate diagnostic groups in alcohol-related cognitive disorders, future studies are needed to establish the criterion validity of learning curves in this population.

Neurocognitive function outcomes in NRG/RTOG 0534, the SPPORT trial.

12022 Background: RTOG 0534 established the benefit of adding of short term androgen deprivation therapy (PBRT+STADT, Arm 2) to prostate bed salvage radiotherapy (PBRT, Arm 1), and demonstrated that elective pelvic lymph node irradiation combined with STADT (PBRT+STADT+PLNRT, Arm 3) results in further reductions in progression. Longitudinal monitoring of neurocognitive function (NCF) was conducted to evaluate the hypothesis that patients treated with STADT will demonstrate greater decline in NCF compared to patients receiving PBRT alone. Methods: Patients were administered the Clinical Trial Battery [Hopkins Verbal Learning Test – Revised (HVLT-R), Trail Making Test (TMT), and the Controlled Oral Word Association (COWA) test] by certified test administrators at baseline, and at 6 weeks (6w), 1 year (1yr), and 5 years after the end of RT (5yr). Raw NCF tests scores were converted to standardized z-scores adjusted for age and education when necessary. Analyses included z-score change and reliable change index (RCI) determined decline compared to baseline, and longitudinal mixed effect regression models using z-scores. To control for multiplicity, p &lt; 0.025 is required for statistical significance. Results: Among the 1716 analyzable patients, 429 consented to NCF monitoring. There were no significant differences in sociodemographic or clinical characteristics between arms. NCF test completion was 82, 76, 63 and 30% at baseline, 6w, 1yr, and 5yr, respectively. RCI-based NCF deterioration was more frequent in Arm 3 compared to Arm 1 at 6 weeks on Delayed Recall (16% vs. 7%, p = 0.023). Patients in Arm 3 evidenced greater z-score decline compared to patients in Arm 1 at 6w on HVLT-R Total Recall [M(SD) Z-score∆ = -0.1(1.0) vs 0.2(0.9), (p = 0.020)] and Delayed Recall [M(SD) Z-score∆ = -0.4(1.5) vs 0.1(1.2), (p = 0.012)]. Mixed effects models identified statistically significant differences in z-scores between Arm 3 and 1 at 6w on Delayed Recall [-0.541 (SE 0.178, p = 0.002)]. A statistically significant difference was observed between Arm 2 and 1 at 6w on TMTB [1.498 (SE 0.626, p = 0.017) favoring Arm 2]. Between arm differences were not seen at any other time point, or on other NCF outcomes. Conclusions: Compared to patients treated with PBRT alone, patients treated with PBRT+STADT+PLNRT exhibited greater worsening in episodic verbal learning and memory processes at 6 weeks after the end of RT, while patients treated with PBRT+STADT exhibited greater improvement in processing speed. The absence of long term or progressive cognitive decline associated with STADT-containing regimens is promising but limited by substantial missing data at year 5. FUNDING This project was supported by grants 10CA180868 (NRG Oncology Operations), U10CA180822 (NRG Oncology SDMC), CTEP from the National Cancer Institute (NCI). Clinical trial information: NCT00567580 .

The Effect of Self-Reported Visual Impairment and Sleep on Cognitive Decline: Results of the Hispanic Community Health Study/Study of Latinos.

Visual impairment could worsen sleep/wake disorders and cognitive decline. To examine interrelations among self-reported visual impairment, sleep, and cognitive decline in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) Miami-site. HCHS/SOL Miami-site participants ages 45-74 years (n = 665) at Visit-1, who returned for cognitive test 7-years later (SOL-INCA). Participants completed the National Eye Institute Visual Functioning Questionnaire (NEI-VFQ), validated sleep questionnaires and test for obstructive sleep apnea (OSA) at Visit-1. We obtained verbal episodic learning and memory, verbal fluency, processing speed, and executive functioning at Visit-1 and at SOL-INCA. Processing speed/executive functioning were added to SOL-INCA. We examined global cognition and change using a regression-based reliable change index, adjusting for the time lapse between Visit-1 and SOL-INCA. We used regression models to test whether 1) persons with OSA, self-reported sleep duration, insomnia, and sleepiness have an increased risk for visual impairment, 2a) visual impairment is associated with worse cognitive function and/or decline, and 2b) sleep disorders attenuate these associations. Sleepiness (β= 0.04; p < 0.01) and insomnia (β= 0.04; p < 0.001) were cross-sectionally associated with visual impairment, adjusting for sociodemographic characteristics, behavioral factors, acculturation, and health conditions. Visual impairment was associated with lower global cognitive function at Visit-1 (β= -0.16; p < 0.001) and on average 7-years later (β= -0.18; p < 0.001). Visual impairment was also associated with a change in verbal fluency (β= -0.17; p < 0.01). OSA, self-reported sleep duration, insomnia, and sleepiness did not attenuate any of the associations. Self-reported visual impairment was independently associated with worse cognitive function and decline.

Sleep, self‐reported ocular health, and cognition in the Hispanic Community Health Study/Study of Latinos (HCHS/SOL) and SOL‐Investigation of Neurocognitive Aging (SOL‐INCA)

Abstract/ProposalBackgroundVisually impaired individuals may experience increased frequency of sleep/wake disorders, fragmented sleep, insomnia, and short sleep duration. Visual impairment and sleep disorders can have downstream effects on cognitive functioning.MethodSample included n = 590 (unweighted) HCHS/SOL Miami Field Center participants ages 45‐74 at baseline who returned for cognitive examination on average 7‐years later (SOL‐INCA). Participants completed validated ocular (National Eye Institute Visual Functioning Questionnaire; NEI‐VFQ), validated sleep questionnaires for sleepiness, insomnia, sleep duration and objective measures of sleep apnea visit‐1 (2008‐2011). They also completed a battery of neurocognitive tests for verbal episodic learning and memory (Brief Spanish English Verbal Learning Test), verbal fluency (Controlled Oral Word Association), processing speed and executive function (Digit Symbol Substitution) at visit‐1 and at SOL‐INCA. Two additional measures of processing speed/executive functioning were added at SOL‐INCA(Trails‐A, ‐B). We examined global cognitive performance and change using a regression‐based reliable change index, adjusting for the time lapse between visit 1 and SOL‐INCA (all measured in z‐score units). We used regression models to test whether (1) participants with sleep disorders have an increased risk for visual impairment, (2a) ocular health is associated with worse baseline and average 7‐years cognitive function and/or cognitive decline, and (2b) sleep attenuates any of these associations.ResultSleepiness (β = 0.04; p&lt;0.01) and insomnia (β = 0.03; p&lt;0.001) were linked to worse ocular health, and the associations were robust to adjustment for sociodemographic characteristics, acculturation, behavioral risk measures, and health conditions. Worse ocular health was linked to lower global cognitive function at baseline (β = ‐0.14; p&lt;0.001) and on average 7‐years later (β = ‐0.16; p&lt;0.01). The associations were consistent across all considered cognitive domains and robust to demographic adjustments. Ocular health was also associated with a change in verbal fluency (β = ‐0.17; p&lt;0.05), but no change was observed in other cognitive domains. Sleep disorders did not attenuate any of the reported associations.ConclusionSelf‐reported ocular health was independently associated with worse language, memory, and executive function and predicted 7‐year cognitive decline in the language domain.

Investigating Neurophysiological Markers of Symptom Severity in Alzheimer's Disease.

Alzheimer's disease (AD) is characterized by a progressive decline in cognitive functioning for which there is a stark lack of effective treatments. Investigating the neurophysiological markers of symptom severity in AD may aid in the identification of alternative treatment targets. In the current study we used a multimodal approach to investigate the association between functional connectivity (specifically between scalp electrodes placed over frontal and parietal regions) and symptom severity in AD, and to explore the relationship between connectivity and cortical excitability. 40 people with AD (25 mild severity, 15 moderate severity) underwent neurobiological assessment (resting state electroencephalography (EEG) and prefrontal transcranial magnetic stimulation (TMS) with EEG) and cognitive assessment. Neurobiological outcomes were resting state functional connectivity and TMS-evoked potentials. Cognitive outcomes were scores on the Alzheimer's Disease Assessment Scale-Cognitive Subscale, Mini-Mental Status Examination, and a measure of episodic verbal learning. Greater contralateral functional theta connectivity between frontal scalp electrodes and parietal scalp electrodes was associated with poorer cognitive performance. In addition, significant correlations were seen between the contralateral theta connectivity and the N100 and P60 TMS-evoked potentials measured from electrodes over the left dorsolateral prefrontal cortex. Together these findings provide initial support for the use of multimodal neurophysiological approaches to investigate potential therapeutic targets in AD. Suggestions for future research are discussed.

Consequences of mesial temporal sparing temporal lobe surgery in medically refractory epilepsy

ObjectiveWe compared long-term seizure outcome, neuropsychological outcome, and occupational outcome of anterior temporal lobectomy (ATL) with and without sparing of mesial structures to determine whether mesial sparing temporal lobectomy prevents memory decline and thus disability, with acceptable seizure outcome. MethodsWe studied patients (n = 21) and controls (n = 21) with no evidence of mesial temporal sclerosis (MTS) on MRI who had surgery to treat drug-resistant epilepsy. Demographic and pre- and postsurgical clinical characteristics were compared. Patients had neuropsychological assessment before and after surgery. Neuropsychological analyses were limited to patients with left-sided surgery and available data (n = 14 in each group) as they were at risk of verbal memory impairment. The California Verbal Learning Test II (CVLT-II) (sum of trials 1–5, delayed free recall) and the Logical Memory subtest of the Wechsler Memory Scale III or IV (WMS-III or WMS-IV) (learning and delayed recall of prose passages) were used to assess verbal episodic learning and memory. Seizure and occupational outcomes were assessed. ResultsThe chance of attaining seizure freedom was similar in the two groups, so sparing mesial temporal structures did not lessen the chance of stopping seizures. Sparing mesial temporal structures mitigated the extent of postoperative verbal memory impairment, though some of these individuals suffered decline as a consequence of surgery. Occupational outcome was similar in both groups. SignificanceMesial temporal sparing resections provide a similar seizure outcome as ATL, while producing a better memory outcome. Anterior temporal lobectomy including mesial structure resection did not increase the risk of postoperative disability.

How does dementia with Lewy bodies start? prodromal cognitive changes in REM sleep behavior disorder.

We describe the progression of cognitive decline and identify the predictive values of cognitive tests in three groups of REM sleep behavior disorder (RBD) patients classified at their last follow-up as having Parkinson's disease (PD), dementia with Lewy bodies (DLB), or still-idiopathic. Patients (n = 109) underwent polysomnographic, neurological, and neuropsychological assessments. We used linear mixed-model analyses to compare the progression of cognitive test performance between the three groups over a 3-year prodromal period, and performed linear regressions for a 6-year prodromal period. We compared the proportions of patients with clinically impaired performance (z scores < -1.5). DLB patients were pair-matched according to age, sex, and education to healthy controls (2:1 ratio), and receiver operating characteristic curves were performed to identify the psychometric properties of cognitive tests to predict dementia. At follow-up, 38 patients (35%) developed a neurodegenerative disorder: 20 had PD and 18 DLB. Cognitive performance changes over time were strongly associated with later development of dementia. Clear deficits in attention and executive functions were observed 6 years before diagnosis. Verbal episodic learning and memory deficits started later, deviating from normal approximately 5 to 6 years and becoming clinically impaired at 1 to 2 years before diagnosis. Visuospatial abilities progressed variably, with inconsistent prodromal latencies. The Trail Making Test (part B), Verbal Fluency (semantic), and Rey Auditory-Verbal Learning Test (total, immediate, and delayed recalls) were the best predictors for dementia (area under the curve = 0.90-0.97). Prodromal DLB is detectible up to 6 years before onset. For clinical utility, the Trail Making Test (part B) best detects early prodromal dementia stages, whereas Verbal Fluency (semantic) and verbal episodic learning tests are best for monitoring changes over time. Ann Neurol 2018;83:1016-1026.

Blood Pressure and Hispanic/Latino Cognitive Function: Hispanic Community Health Study/Study of Latinos Results.

Hispanics/Latinos are at increased risk for cardiovascular disease and cognitive decline and dementias. High blood pressure (BP) has been implicated in both stroke and dementias. Associations between BP and cognition among diverse Latinos are still unpublished. We examined associations between cognition and four BP based measures among diverse Hispanics/Latinos. We hypothesized that higher BP, particularly systolic pressure, and increased arterial stiffness (i.e., pulse pressure), would be associated with lower cognitive function. We used baseline (2008-2011) Hispanic Community Health Study/Study of Latinos (HCHS/SOL; n = 9,019; ages 45-74 years) data to examine cognition in relation to BP measures. In age, sex, and education adjusted models, systolic, pulse, and mean arterial pressure were consistently negatively associated with executive function, psychomotor speed and sustained attention, verbal episodic learning and memory, speech fluency, and mental status measures. These associations were attenuated but remained statistically significant in fully adjusted models. Among middle-aged and older diverse Hispanics/Latinos, we found modest but consistent associations between indicators of arterial stiffness, and compromised blood flow and lower cognitive function. Clinical management and public health interventions to raise awareness and enhance BP management beginning in midlife could reduce disparities and improve population health by reducing cognitive decline burdens.

Working Memory Deficit as a Risk Factor for Severe Apathy in Schizophrenia: A 1-Year Longitudinal Study.

Apathy, described as impaired motivation and goal-directed behavior, is a common yet often overlooked multidimensional psychopathological state in schizophrenia. Its underlying cognitive processes remain largely unexplored. Data was drawn from a longitudinal hospital study of patients with a DSM-IV diagnosis of schizophrenia; 137 (82.5%) participated at the 1-month follow-up and 81 (59.1%) at the 1-year follow-up. Apathy was assessed with the Lille Apathy Rating Scale, validated in French and in schizophrenia. Severe apathy, overall (total score > -13) and on 4 previously identified distinct dimensions, was considered. Episodic verbal learning was assessed with the California Verbal Learning Test, executive functioning with the Trail Making Test, the Six Element Test and the Stop Signal Paradigm and working memory with the Letter-Number Sequencing Test. After controlling for confounding variables, only episodic verbal learning was associated with severe overall apathy in the cross-sectional study. At 1 year, working memory was associated with an increased risk of severe overall apathy, adjusting for baseline apathy. Using a dimensional approach to apathy, specific types of cognition were found to be associated with specific dimensions of apathy. Our findings confirm the need for a multidimensional approach of negative symptoms in schizophrenia. Moreover, cognitive functioning could be a risk factor for developing severe apathy. Cognitive remediation may thus be a useful non-pharmacological intervention for treating apathy in schizophrenia patients.

The 12 Years Preceding Mild Cognitive Impairment Due to Alzheimer's Disease: The Temporal Emergence of Cognitive Decline.

Background: The identification of the type and sequence of cognitive decline in preclinical mild cognitive impairment (MCI) prior to Alzheimer’s disease (AD) is crucial for understanding AD pathogenesis and implementing therapeutic interventions.Objective: To model the longitudinal courses of different neuropsychological functions in MCI due to AD.Methods: We investigated the prodromal phase of MCI over a 12-year period in 27 initially healthy participants with subsequent MCI preceding AD (NC-MCI) and 60 demographically matched healthy individuals (NC-NC). The longitudinal courses of cognitive performance (verbal and visual episodic memory, semantic memory, executive functioning, constructional praxis, psychomotor speed, language, and informant-based reports) were analyzed with linear mixed effects models.Results: The sequence with which different cognitive functions declined in the NC-MCI relative to the NC-NC group began with verbal memory and savings performance approximately eight years, and verbal episodic learning, visual memory, and semantic memory (animal fluency) circa four years prior to the MCI diagnosis. Executive functioning, psychomotor speed, and informant-based reports of the NC-MCI group declined approximately two years preceding the MCI diagnosis.Conclusions: Measurable neuropsychological deterioration occurs up to approximately eight years preceding MCI due to AD.

Serum 25-hydroxyvitamin D is associated with reduced verbal episodic memory in healthy, middle-aged and older adults

There is increasing evidence supporting an association of higher serum vitamin D concentration with better cognitive performance in older individuals. However, to date, consideration of the putative association between vitamin D and cognition has been based principally on studies investigating clinical participant samples manifesting vitamin D deficiency, particularly in older people. Moreover, relationships between vitamin D and cognition are typically not considered in the context of counter-regulatory calcium-modulating hormones or calcium homeostasis. Serum vitamin D/bioactive (ionised) calcium/parathyroid hormone homeostasis was considered in the context of cognitive performance in healthy, middle-aged and older individuals. A cross-sectional sample of 179 participants between the ages of 47-84years was recruited for this study (114 females, 65 males). Participants provided fasting blood samples for analysis of serum 25-hydroxyvitamin D levels, ionised calcium (iCa) and parathyroid hormone (PTH) and completed cognitive measures of verbal episodic learning and memory. Serum 25-hydroxyvitamin D concentrations were negatively associated (with and without covariates of age, gender, depression and NART scores, iCa, and PTH) with measures of verbal episodic learning and memory, in particular with trial 5 of the Rey Auditory Verbal Learning Test (RAVLT) and long-delay free recall on the RAVLT. Overall, the findings from this study suggest an association between higher vitamin D status and poorer performance on verbal episodic memory in middle-aged and older individuals with normal vitamin D-calcium-PTH homeostasis. Despite requiring replication in other participant samples, this is a potentially important finding as it indicates that it may not be beneficial from a cognitive perspective to provide vitamin D supplements in individuals with already adequate vitamin D status.

Bone mineral density, adiposity, and cognitive functions.

Cognitive decline and dementia due to Alzheimer's disease (AD) have been associated with genetic, lifestyle, and environmental factors. A number of potentially modifiable risk factors should be taken into account when preventive or ameliorative interventions targeting dementia and its preclinical stages are investigated. Bone mineral density (BMD) and body composition are two such potentially modifiable risk factors, and their association with cognitive decline was investigated in this study. 164 participants, aged 34–87 years old (62.78 ± 9.27), were recruited for this longitudinal study and underwent cognitive and clinical examinations at baseline and after 3 years. Blood samples were collected for apolipoprotein E (APOE) genotyping and dual energy x-ray absorptiometry (DXA) was conducted at the same day as cognitive assessment. Using hierarchical regression analysis, we found that BMD and lean body mass, as measured using DXA were significant predictors of episodic memory. Age, gender, APOE status, and premorbid IQ were controlled for. Specifically, the List A learning from California Verbal Learning Test was significantly associated with BMD and lean mass both at baseline and at follow up assessment. Our findings indicate that there is a significant association between BMD and lean body mass and episodic verbal learning. While the involvement of modifiable lifestyle factors in human cognitive function has been examined in different studies, there is a need for further research to understand the potential underlying mechanisms.

Subjective memory complaint only relates to verbal episodic memory performance in mild cognitive impairment.

A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood. We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI. MCI participants were drawn from the Alzheimer's Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n = 191, 77 ± 7 years; complaint n = 206, 73 ± 8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness). Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E4 status, found that cognitive complaint related to immediate (β = -1.07, p < 0.001) and delayed episodic memory performances assessed on a serial list learning task (β = -1.06, p = 0.001) but no other cognitive measures or neuroimaging markers. Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer's disease, across the cognitive aging spectrum.

Distinct episodic verbal memory profiles in schizophrenia.

According to some authors, episodic memory impairment may be a feature shared by all schizophrenic patients, whereas others argue in favor of the mnesic heterogeneity. Our aims were to determine whether patients can be grouped based on according to their mnesic performances. The California Verbal Learning Test (CVLT), an episodic verbal learning test, was compared in 61 schizophrenic patients and 61 matched healthy subjects. The 32 indices were calculated using CVLT Scoring Software. This process allowed us to describe patients’ episodic processes in detail (encoding, storage, retrieval). We isolated one group with normative data, another showed impairment of both encoding and retrieval processes, and in the last one, only encoding process was impaired. As schizophrenia is heterogeneous with regard to episodic memory, impairments should not be considered as a common core to the various forms of the illness and it would be fruitful to systematically assess episodic processes in detail to take into account individual abilities and challenges.

G06 Verbal learning and memory in preclinical Huntington's disease

BackgroundHuntington's disease (HD) is associated with progressive cognitive impairments.AimsThe aim of this ongoing study was to examine verbal episodic learning and memory in preclinical HD.MethodsParticipants were recruited from the predictive...

Olfactory dysfunction, central cholinergic integrity and cognitive impairment in Parkinson's disease

Olfactory dysfunction is common in subjects with Parkinson’s disease. The pathophysiology of such dysfunction, however, remains poorly understood. Neurodegeneration within central regions involved in odour perception may contribute to olfactory dysfunction in Parkinson’s disease. Central cholinergic deficits occur in Parkinson’s disease and cholinergic neurons innervate regions, such as the limbic archicortex, involved in odour perception. We investigated the relationship between performance on an odour identification task and forebrain cholinergic denervation in Parkinson’s disease subjects without dementia. Fifty-eight patients with Parkinson’s disease (mean Hoehn and Yahr stage 2.5 ± 0.5) without dementia (mean Mini-Mental State Examination, 29.0 ± 1.4) underwent a clinical assessment, [11C]methyl-4-piperidinyl propionate acetylcholinesterase brain positron emission tomography and olfactory testing with the University of Pennsylvania Smell Identification Test. The diagnosis of Parkinson’s disease was confirmed by [11C]dihydrotetrabenazine vesicular monoamine transporter type 2 positron emission tomography. We found that odour identification test scores correlated positively with acetylcholinesterase activity in the hippocampal formation (r = 0.56, P < 0.0001), amygdala (r = 0.50, P < 0.0001) and neocortex (r = 0.46, P = 0.0003). Striatal monoaminergic activity correlated positively with odour identification scores (r = 0.30, P < 0.05). Multiple regression analysis including limbic (hippocampal and amygdala) and neocortical acetylcholinesterase activity as well as striatal monoaminergic activity, using odour identification scores as the dependent variable, demonstrated a significant regressor effect for limbic acetylcholinesterase activity (F = 10.1, P < 0.0001), borderline for striatal monoaminergic activity (F = 1.6, P = 0.13), but not significant for cortical acetylcholinesterase activity (F = 0.3, P = 0.75). Odour identification scores correlated positively with scores on cognitive measures of episodic verbal learning (r = 0.30, P < 0.05). These findings indicate that cholinergic denervation of the limbic archicortex is a more robust determinant of hyposmia than nigrostriatal dopaminergic denervation in subjects with moderately severe Parkinson's disease. Greater deficits in odour identification may identify patients with Parkinson's disease at risk for clinically significant cognitive impairment.

Evaluating the Relationship between Memory Functioning and Cingulum Bundles in Acute Mild Traumatic Brain Injury Using Diffusion Tensor Imaging

Compromised memory functioning is one of the commonly reported cognitive sequelae seen following mild traumatic brain injury (mTBI). Diffusion tensor imaging (DTI) has been shown to be sufficiently sensitive at detecting early microstructural pathological alterations after mTBI. Given its location and shape, the cingulate, which is comprised of the cingulate gyrus (gray matter) and cingulum bundles (white matter), is selectively vulnerable to mTBI. In this study we examined the integrity of cingulum bundles using DTI, and the relationship between cingulum bundles and memory functioning. Twelve adolescents with mTBI and 11 demographically-matched healthy controls were studied. All participants with mTBI had a Glasgow Coma Scale score of 15, and were without intracranial findings on CT scan. Brain scans were performed on average 2.92 days post-injury, and all participants were administered the Verbal Selective Reminding Test (VSRT), an episodic verbal learning and memory task. Participants with mTBI had a significantly lower apparent diffusion coefficient (ADC) bilaterally than controls (p < 0.001). Despite the marginal significance of the group difference in fractional anisotropy (FA), the effect size between groups was moderate (d = 0.66). Cognitively, healthy controls performed better than the TBI group on immediate and delayed recall; however, the difference did not reach statistical significance. In the mTBI group, FA of the left cingulum bundle was significantly correlated with 30-min delayed recall (r = -0.56, p = 0.05). A marginally significant correlation was found between ADC of the left cingulum bundle and the total words of immediate recall (r = 0.59, p = 0.07). No significant correlation was found between DTI metrics and memory functioning for the control group. These preliminary findings indicate that cingulate injury likely contributes to the cognitive sequelae seen during the early phase post-mTBI.

Cognitive effects of treating obstructive sleep apnea in Alzheimer's disease: a randomized controlled study.

To examine whether treatment of obstructive sleep apnea (OSA) with continuous positive airway pressure (CPAP) in patients with Alzheimer's disease (AD) results in better cognitive function. Randomized double-blind placebo-controlled trial. Participants were randomized to therapeutic CPAP for 6 weeks or placebo CPAP for 3 weeks followed by therapeutic CPAP for 3 weeks. General clinical research center. Fifty-two men and women with mild to moderate AD and OSA. CPAP. A complete neuropsychological test battery was administered before treatment and at 3 and at 6 weeks. A comparison of subjects randomized to 3 weeks of therapeutic versus placebo CPAP suggested no significant improvements in cognition. A comparison of pre- and posttreatment neuropsychological test scores after 3 weeks of therapeutic CPAP in both groups showed a significant improvement in cognition. The study was underpowered to make definitive statements about improvements within specific cognitive constructs, although exploratory post hoc examination of change scores for individual tests suggested improvements in episodic verbal learning and memory and some aspects of executive functioning such as cognitive flexibility and mental processing speed. OSA may aggravate cognitive dysfunction in dementia and thus may be a reversible cause of cognitive loss in patients with AD. OSA treatment seems to improve some cognitive functioning. Clinicians who care for patients with AD should consider implementing CPAP treatment when OSA is present.

Construct validity of Hopkins Verbal Learning Test—Revised component process measures in an HIV-1 sample

Executive dyscontrol of episodic verbal learning and memory secondary to prefrontostriatal circuit neuropathophysiology is a common feature of HIV-1 infection. Prior research indicates that standard clinical learning and recall indexes from Hopkins Verbal Learning Test—Revised (HVLT-R) are among the most sensitive indicators of HIV-associated neurocognitive disorders. Emerging data support the validity of qualitative component process measures derived from the HVLT-R (e.g., Semantic Clustering); however, no prior studies have examined these particular indices of performance in an HIV-1-infected population. In the present study, we examined the construct validity of HVLT-R component process indices in a sample of 42 persons with HIV-1 infection and 29 demographically similar seronegative comparison participants. The HIV-1 sample performed significantly below the seronegative group on Total and Delayed Recall, Semantic Clustering, and the Retrieval Index. No between-group differences were observed on Serial Clustering, Pair Frequency, Learning, Repetitions, Semantic False Positive Recognition Errors, or the Recognition Discrimination Index. In addition, the HVLT-R component process measures demonstrated evidence of convergent and divergent validity with standard clinical tests in the HIV-1 sample. Findings support the construct validity of HVLT-R component process measures and are commensurate with prior literature indicating that HIV-1 disease is associated with deficient executive control of encoding and retrieval within verbal episodic memory.