Verbal Episodic Memory Tests Research Articles

Combining Cognitive Markers to Identify Individuals at Increased Dementia Risk: Influence of Modifying Factors and Time to Diagnosis.

We investigated the extent to which combining cognitive markers increases the predictive value for future dementia, when compared to individual markers. Furthermore, we examined whether predictivity of markers differed depending on a range of modifying factors and time to diagnosis. Neuropsychological assessment was performed for 2357 participants (60+ years) without dementia from the population-based Swedish National Study on Aging and Care in Kungsholmen. In the main sample analyses, the outcome was dementia at 6 years. In the time-to-diagnosis analyses, a subsample of 407 participants underwent cognitive testing 12, 6, and 3 years before diagnosis, with dementia diagnosis at the 12-year follow-up. Category fluency was the strongest individual predictor of dementia 6 years before diagnosis [area under the curve (AUC) = .903]. The final model included tests of verbal fluency, episodic memory, and perceptual speed (AUC = .913); these three domains were found to be the most predictive across a range of different subgroups. Twelve years before diagnosis, pattern comparison (perceptual speed) was the strongest individual predictor (AUC = .686). However, models 12 years before diagnosis did not show significantly increased predictivity above that of the covariates. This study shows that combining markers from different cognitive domains leads to increased accuracy in predicting future dementia 6 years later. Markers from the verbal fluency, episodic memory, and perceptual speed domains consistently showed high predictivity across subgroups stratified by age, sex, education, apolipoprotein E ϵ4 status, and dementia type. Predictivity increased closer to diagnosis and showed highest accuracy up to 6 years before a dementia diagnosis. (JINS, 2020, 00, 1-13).

Relationship Between PET-Assessed Amyloid Burden and Visual and Verbal Episodic Memory Performance in Elderly Subjects.

Studies of elderly subjects using biomarkers that are proxies for Alzheimer's disease (AD) pathology have the potential to document meaningful relationships between cognitive performance and biomarker changes along the AD continuum. To document cognitive performance differences across distinct AD stages using a categorization based on the presence of PET-assessed amyloid-β (Aβ) burden and neurodegeneration. Patients with mild dementia compatible with AD (n = 38) or amnestic mild cognitive impairment (aMCI; n = 43) and a cognitively unimpaired group (n = 27) underwent PET with Pittsburgh compound-B (PiB) assessing Aβ aggregation (A+) and [18F]FDG-PET assessing neurodegeneration ((N)+). Cognitive performance was assessed with verbal and visual episodic memory tests and the Mini-Mental State Examination. The A+(N)+ subgroup (n = 32) showed decreased (p < 0.001) cognitive test scores compared to both A+(N)-(n = 18) and A-(N)-(n = 49) subjects, who presented highly similar mean cognitive scores. Despite its modest size (n = 9), the A-(N)+ subgroup showed lower (p < 0.043) verbal memory scores relative to A-(N)-subjects, and trend lower (p = 0.096) scores relative to A+(N)-subjects. Continuous Aβ measures (standard uptake value ratios of PiB uptake) were correlated most significantly with visual memory scores both in the overall sample and when analyses were restricted to dementia or (N)+ subjects, but not in non-dementia or (N)-groups. These results demonstrate that significant Aβ-cognition relationships are highly salient at disease stages involving neurodegeneration. The fact that findings relating Aβ burden to memory performance were detected only at (N)+ stages, together with the similarity of test scores between A+(N)-and A-(N)-subjects, reinforce the view that Aβ-cognition relationships during early AD stages may remain undetectable unless substantially large samples are evaluated.

EXAMINING THE RELATIONSHIP BETWEEN COGNITIVE FUNCTIONING AND SUBJECTIVE WELL-BEING ACROSS AGE

Higher levels of subjective well-being (SWB) are associated with myriad of positive outcomes, including better physical health. Several variables have been shown to predict SWB, including cognitive functioning. The relationship between aspects of SWB (positive affect, negative affect, and life satisfaction) and cognition were examined in participants (N = 5, 125) between the ages of 18- 99 years from the Virginia Cognitive Aging Project (VCAP). Participants completed a battery of cognitive tasks, including tests of verbal episodic memory, processing speed, reasoning, spatial visualization, and vocabulary. Cross-sectional analyses were conducted using structural equation modeling, using full information maximum likelihood estimation. In the models, the five latent cognitive constructs simultaneously predicted each of the SWB outcome variables separately. Age, education, gender, and self-rated health were included as covariates. Results show that reasoning was a significant unique predictor of negative affect (-.30), vocabulary was a significant unique predictor of positive affect (-.21), and spatial visualization was a significant unique predictor of life satisfaction (.21). Age moderation was examined by dividing the sample into three age groups (younger, middle-aged, and older). There was some evidence of age moderation. Namely, spatial visualization was a significant unique predictor of life satisfaction in the younger sample only. Reasoning and processing speed predicted negative affect in the younger group, whereas only reasoning predicted negative affect in the older group. In conclusion, in a large community-based sample spanning adulthood, there is evidence that cognition predicts aspects of SWB but there is variation across SWB outcome variables, and across age.

Association of Estradiol and Visceral Fat With Structural Brain Networks and Memory Performance in Adults

Changes in estradiol during aging are associated with increased dementia risk. It remains unclear how estradiol supports cognitive health and whether risk factors, such as midlife obesity, are exacerbated by estrogen loss. To assess whether visceral adipose tissue (VAT) moderates the association between age and brain network structure and to investigate whether estradiol moderates the association between VAT and brain network structure. Cross-sectional study of data from 974 cognitively healthy adults in Germany who participated in the Health Study of the Leipzig Research Centre for Civilization Diseases, a previously described population-based cohort study. Two moderation analyses were performed, including VAT as the moderator variable between age and brain network structure and estradiol as the moderator variable between VAT and brain network structure. The study was conducted from August 1, 2011, to November 23, 2014. Analyses were conducted from August 2017 to September 2018. Serum estradiol levels from fasting blood and visceral adipose tissue volume from T1-weighted magnetic resonance imaging (MRI). Brain network covariance (individual loading on structural network derived from T1-weighted MRI) and memory performance (composite score from the Consortium to Establish a Registry for Alzheimer Disease [CERAD] verbal episodic memory test on learning [score range, 0-30], recall [score range, 0-10], and recognition [score range, 0-20]). Final analyses included data from 473 women (mean [SD] age, 50.10 [15.63] years) and 501 men (mean [SD] age, 51.24 [15.67] years). Visceral adipose tissue was associated with an exacerbation of the negative association of aging with network covariance for women (interaction term β = -0.02; 95% bias-corrected bootstrap CI, -0.03 to -0.01; P = .001) and men (interaction term β = -0.02; 95% bias-corrected bootstrap CI, -0.03 to -0.01; P < .001). Estradiol level was associated with a reduction in the negative association of VAT with network covariance in women (interaction term β = 0.63; 95% bias-corrected bootstrap CI, 0.14-1.12; P = .01), with no significant association in men. In the female midlife subgroup (age range, 35-55 years, when menopause transition occurs), low estradiol levels were associated with lower memory network covariance (Cohen d = 0.61; t80 = 2.76; P = .007) and worse memory performance (Cohen d = 0.63; t76 = 2.76; P = .007). This study reports a novel association between VAT, estradiol, and structural brain networks as a potential mechanism underlying cognitive decline in women. These findings appear to highlight the need for sex-specific strategies, including VAT and hormonal screening during midlife, to support healthy cognitive aging.

Women Outperform Men in Verbal Episodic Memory Even in Oldest-Old Age: 13-Year Longitudinal Results of the AgeCoDe/AgeQualiDe Study.

Sex differences in verbal episodic memory function have been widely reported. However, sex-specific effects on rates of episodic memory decline remain controversial, and evidence is particularly scarce in the oldest-old population. We aimed to investigate sex differences in trajectories of episodic memory performance in oldest-old individuals. Based on 13-year longitudinal data with 9 follow-up assessments of a large sample of cognitively unimpaired old (75+) primary care patients (n = 3,254) participating in the German AgeCoDe/AgeQualiDe study, we used linear mixed effects analyses to model sex-specific trajectories of change in verbal episodic memory while accounting for covarying factors. We found that even in the highest age group women outperformed men in immediate (b = -1.71, p < 0.001) and delayed (b = -0.85, p < 0.001) free recall conditions. Associated late-life trajectories, however, did not differ significantly between the sexes. We further demonstrated that younger age, higher education, and an absence of depressive symptoms predicted better performance in both sexes. In contrast, past occurrences of stroke and APOE ɛ4 carrier status showed a negative relation to test scores. Our findings confirm previous research suggesting that women perform better in verbal episodic memory tests. We add that this advantage is still present in the oldest-old age groups. Our results indicate that sociodemographic and health related factors are as important as genetically based APOE ɛ4 carrier status in the prediction of normal cognitive development in advanced old age.

Robust norms for neuropsychological tests of verbal episodic memory in Australian women.

Robust norms for neuropsychological tests may offer superior clinical utility to conventional norms, in their ability to distinguish normal cognitive aging from prodromal dementia. However, the availability of robust norms from midlife, where cognitive changes in those at risk of disease may arise, is limited. This study presents demographically stratified robust norms for tests of verbal memory in Australian women. Participants were from the population-based Women's Healthy Ageing Project. Baseline (1999 to 2002; n = 368; age range = 53-67years) and follow-up (2012 to 2014; n = 291; age range = 65-80years) measures of word-list and story recall were administered at least 10 years apart. Four samples were identified: conventional (derived from a cross-sectional sample), robust (derived from a longitudinal sample), mild cognitive impairment (MCI) or Alzheimer's disease (AD), and lost to follow-up. Area under the curve (AUC) values were generated to assess the diagnostic ability of conventional and robust norms using 1 standard deviation and 1.5 standard deviation cut-offs. There were differences between conventional Australian and American normative data for the Consortium to Establish a Registry for Alzheimer's Disease word-list recall. Individuals who declined to MCI/AD over the follow-up displayed poorer performance at baseline, however no differences in classification ability of robust (AUC range .54 to.64) and conventional (AUC range .51 to .65) norms were observed. Neuropsychological performance in midlife predicted clinical cognitive decline 1 decade later, but conventional and robust norms was similarly predictive of conversion to disease in this cohort. The use of country-specific, representative conventional norms remains a valuable tool for neuropsychologists to assess cognitive performance throughout midlife. (PsycINFO Database Record (c) 2019 APA, all rights reserved).

Visual and Verbal Serial List Learning in Patients with Statistically-Determined Mild Cognitive Impairment.

Background and ObjectivePrior research with patients with mild cognitive impairment (MCI) suggests that visual versus verbal episodic memory test performance may be more sensitive to emergent illness. However, little research has examined visual versus verbal episodic memory performance as related to MCI subtypes.Research Design and MethodsPatients were diagnosed with non-MCI, amnestic MCI (aMCI), and combined mixed/dysexecutive MCI (mixed/dys MCI). Visual and verbal episodic memory were assessed with the Brief Visuospatial Memory Test-Revised (BVMT-R) and the 12-word Philadelphia (repeatable) Verbal Learning Test (P[r]VLT), respectively.ResultsBVMT-R and P(r)VLT scores yielded similar between-group patterns of performance. Non-MCI patients scored better than other groups on all parameters. aMCI and mixed/dys MCI did not differ on immediate or delayed free recall. Both delayed BVMT-R and P(r)VLT recognition test performance dissociated all three groups. Logistic regression analyses found that BVMT-R delayed free recall and delayed recognition scores correctly classified more patients with MCI (75.40%) than analogous P(r)VLT scores (66.20%). Visual versus verbal memory within-group analyses found no differences among non-MCI patients; P(r)VLT immediate free recall was worse among aMCI patients, but BVMT-R immediate free recall and delayed recognition were worse among mixed/dys MCI patients.Discussion and ImplicationsBetween-group analyses found convergent patterns of performance such that both tests identified elements of amnesia. However, logistic and within-group analyses found differing performance patterns suggesting that impaired visual episodic memory performance may be specific to emergent illness in mixed/dys MCI. Complementary but divergent neurocognitive networks may underlie visual versus verbal episodic memory performance in some patients with MCI.

Supplemental Material for Robust Norms for Neuropsychological Tests of Verbal Episodic Memory in Australian Women

Supplemental Material for Robust Norms for Neuropsychological Tests of Verbal Episodic Memory in Australian Women

Effects on cognition of 20 days of anodal trans-cranial Direct Current Stimulation (tDCS) over left dorsolateral-pre-frontal cortex (DLPFC) in patients affected by Mild Cognitive Impairment: A case-control study

Mild Cognitive impairment (MCI) affects as long as 15% of population in the elderly. Trans-cranial direct current stimulation (tDCS) is a non invasive technique of neuro-modulation which has proved to influence performances on different cognitive domains. We investigate effects on cognition of 20 days anodal tDCS in 17 MCI patients compared to 17 matched MCI patients. Patients underwent neuropsychological evaluation at baseline and then were randomly assigned to anodal or sham group. tDCS protocol consisted in 20 min, 5 days per week (up to total 20 days), 2 mA anodal stimulation over left dorsolateral pre-frontal cortex (DLPFC). At the end of the last day of stimulation a second neuropsychological evaluation was performed. We compared baseline and after stimulation neuropsychological results in anodal vs sham groups using repeated ANOVA measures as statistical analysis test. At follow-up anodal group showed improvement in verbal episodic memory (p < 0.001) and figure naming test (p < 0.01), in a general index of cognitive function (Brief Mental Deterioration Battery) (p < 0.0001) and in a mood measurement test (Beck Depression Inventory) (p < 0.01). Anodal tCDS can be an useful low-cost and relative risk-free tool to improve cognitive symptoms in MCI.

A computerized, self-administered test of verbal episodic memory in elderly patients with mild cognitive impairment and healthy participants: A randomized, crossover, validation study

IntroductionPerformance of “Revere”, a novel iPad-administered word-list recall (WLR) test, in quantifying deficits in verbal episodic memory, was evaluated versus examiner-administered Rey Auditory Verbal Learning Test (RAVLT) in patients with mild cognitive impairment and cognitively normal participants. MethodsElderly patients with clinically diagnosed mild cognitive impairment (Montreal Cognitive Assessment score 24–27) and cognitively normal (Montreal Cognitive Assessment score ≥28) were administered RAVLT or Revere in a randomized crossover design. ResultsA total of 153/161 participants (Revere/RAVLT n = 75; RAVLT/Revere n = 78) were randomized; 148 (97%) completed study; 121 patients (mean [standard deviation] age: 70.4 [7.84] years) were included for analysis. Word-list recall scores (8 trials) were comparable between Revere and RAVLT (Pearson's correlation coefficients: 0.12–0.70; least square mean difference [Revere-RAVLT]: −0.84 [90% CI, −1.15; −0.54]). Model factor estimates indicated trial (P < .001), period (P < .001) and evaluation sequence (P = .038) as significant factors. Learning over trials index and serial position effects were comparable. DiscussionParticipants' verbal recall performance on Revere and RAVLT were equivalent.

Vitamin D status is associated with executive function a decade later: Data from the Women’s Healthy Ageing Project

ObjectivesVitamin D deficiency has been associated with cognitive decline and dementia in older adults. However, there is a paucity of studies assessing whether this association manifests from midlife. Given the long prodromal stage of dementia, we investigated the association between midlife vitamin D and cognition 10 years later. Study design252 participants (aged 55–67 years) from the Women’s Healthy Ageing Project had baseline (2002) vitamin D and neuropsychological measures assessed. Of these, 170 (aged 65–77 years) had follow-up neuropsychological testing (2012). Outcome measuresSerum 25-hydroxyvitamin D (25[OH]D) was measured using an automated chemiluminescence system. The neuropsychological tests used were: Consortium to Establish a Registry for Alzheimer’s Disease (CERAD), California Verbal Learning Test Second Edition (CVLT-II), verbal fluency and Trail Making Test-B (TMT-B). Composite scores for verbal episodic memory (CERAD and CVLT-II) and executive function (verbal fluency and TMT-B) were obtained by summating standardized scores for each test. ResultsAnalyses were adjusted for age, education and body mass index (BMI). Further adjustment for physical activity, depression, vascular risk factors, supplementation and APOE4-genotype did not materially change the results. At baseline, those with vitamin D>25nmol/L performed better on verbal fluency (β=2.46, 95%CI=0.53,4.40) and TMT-B time (β=-18.23, 95%CI=−32.86,−3.61), with higher executive function (β=1.40, 95%CI=0.44,2.37). These relationships persisted 10 years later for TMT-B (β=-15.38, 95%CI=−30.82,0.07) and executive function (β=1.05, 95%CI=0.14,1.95). There were no associations with tests of verbal episodic memory. ConclusionMidlife vitamin D>25nmol/L is associated with improved aspects of executive function in ageing. Findings highlight a potential therapeutic age window where midlife vitamin D repletion could be neuroprotective against cognitive decline.

COGNITIVE SUPER-AGING VERSUS TYPICAL AGING IN COMMUNITY-DWELLING OLDER ADULTS: LONGITUDINAL TRAJECTORIES IN GLOBAL CORTICAL THICKNESS OVER SIX YEARS

Background It is common for older adults to experience decline in some cognitive functions with increasing age. Importantly, a subset, usually referred to as super-agers (SA; Rogalski, et al., 2013, J Cog Neurosc, 25: 29-36) live to an old age whilst continuing to maintain cognitive function at levels similar to demographically-matched peers at least 20-30 years their junior. The current study reports trajectories of change in cortical thickness on a well-defined group of SAs vs. typical agers (TA) followed longitudinally over six years in the Australian Imaging, Biomarkers & Lifestyle Study (AIBL) (Ellis et al., 2009, Int Psychogeriat, 2: 672-87). Methods Super-Agers were defined as individuals aged 60+ who scored in the normative range for individuals aged 30 – 44 on the CVLT-II, a test of verbal episodic memory, at baseline and two consecutive time-points 18 months apart. SAs additionally must have performed in the unimpaired range in all other cognitive domains, as compared to same-aged peers. Typical agers must have scored within the normal range on all cognitive measures compared with same-aged peers. This report describes data from 21 SAs and 24 TAs. The TAs were chosen from a larger group matched on age, education and gender to the SA group. All participants completed brain magnetic resonance imaging every 18 months for six years. We conducted multiple linear mixed models analyses to assess the association between preservation of cortical thickness in SAs and TAs. Results From 34 regions of interest identified as potentially differentiating SAs from TAs from previous neuroimaging studies, our results were consistent in finding greater cortical thinning amongst TAs in 20 of these regions (p-values ranging between ≤ .000 and .047), with an additional five regions at trend level (p-values ranging between ≥ .05 and .073). Using false discovery rates, we found significantly preserved thickness in three regions not previously reported including left superior parietal gyrus, left precuneus, and left paracentral lobule. Conclusions SAs and TAs displayed similar cortical thickness at baseline (p >.40), but showed different trajectories over time. The findings will be discussed in the context of current models of cognitive and brain reserve.

Effects of Age and Gender on Recall and Recognition Discriminability.

Recall and recognition memory abilities are known to decline with increasing age, yet much of the evidence stems from studies that used simple measures of total target recall or recognition. The California Verbal Learning Test-Second Edition (CVLT-II) includes a new measure of recall discriminability that is analogous to recognition discriminability. These discriminability measures yield more thorough assessments of recall and recognition by accounting for intrusion and false positive errors, respectively. Research also has shown that women outperform men on verbal episodic memory tests. However, gender differences in recall and recognition discriminability and the age-by-gender interaction on these constructs have not been thoroughly examined. Cognitively healthy adults (N = 223) 18-91 years in age completed the CVLT-II. Multiple regression analyses were conducted to examine effects of age, gender, and the age-by-gender interaction on CVLT-II subtypes of recall and recognition discriminability. Discriminability scores decreased with increasing age, and women outperformed men. There was an age-by-gender interaction on total, immediate, and free recall discriminability - the negative association between age and scores was stronger in men than in women. Exploratory analyses revealed an inverted U-shaped relationship between age and recall discriminability scores in women. The present findings support and expand upon the extant literature on aging, gender, and verbal episodic memory, plus describe a novel age-by-gender interaction intrinsic to subtypes of recall discriminability. The findings suggest that methods traditionally used to assess recognition memory function can be used to elucidate age- and gender-related changes in recall ability across the adult lifespan.

Cognitive profile in prodromal dementia with Lewy bodies

BackgroundCortical and subcortical cognitive impairments have been found in dementia with Lewy bodies (DLB). Roughly, they comprise visuoconstructive and executive dysfunction, whereas memory would remain relatively spared. However, the cognitive profile of patients with prodromal DLB remains poorly illustrated to date.MethodsWe included 37 patients with prodromal DLB (age 67.2 ± 8.6 years, 18 men, Mini Mental State Examination [MMSE] score 27.4 ± 2) and 29 healthy control subjects (HCs; age 68.8 ± 7.9 years, 15 men, MMSE score 29.0 ± 0.9). They were presented with an extensive neuropsychological test battery to assess memory; speed of processing; executive function; visuoperceptual, visuospatial and visuoconstructive abilities; language; and social cognition.ResultsCompared with HCs, patients had lower scores on a visual recognition memory test (Delayed Matching to Sample-48 items; p ≤ 0.021) and lower free recall (all p ≤ 0.035), but not total recall, performance on a verbal episodic memory test (Free and Cued Selective Reminding Test). Short-term memory (p = 0.042) and working memory (p = 0.002) scores were also lower in patients. Assessment of executive function showed no slowing but overall lower performance in patients than in HCs (all p ≤ 0.049), whereas assessment of instrumental function yielded mixed results. Indeed, patients had lower scores on language tests (p ≤ 0.022), apraxia for pantomime of tool use (p = 0.002) and imitation of meaningless gesture (p = 0.005), as well as weakened visuospatial abilities (p = 0.047). Visuoconstruction was also impaired in patients. However, visuoperceptual abilities did not differ between groups. Finally, theory of mind abilities were lower in patients than in HCs (p < 0.05), but their emotion recognition abilities were similar.ConclusionsThis study presents the cognitive profile in patients with prodromal DLB. In line with the literature on DLB with dementia, our results show lower performance on tests of executive function and visuoconstruction. However, we found, from a prodromal stage of DLB, memory (free recall and visual recognition) and social cognition deficits, as well as weakened visuospatial and praxic abilities.

Roles of hippocampal subfields in verbal and visual episodic memory

IntroductionSelective hippocampal (HC) subfield atrophy has been reported in older adults with mild cognitive impairment and Alzheimer’s disease. The goal of this study was to investigate the associations between the volume of hippocampal subfields and visual and verbal episodic memory in cognitively normal older adults. MethodsThis study was conducted on a subset of 133 participants from the Einstein Aging Study (EAS), a community-based study of non-demented older adults systematically recruited from the Bronx, N.Y. All participants completed comprehensive EAS neuropsychological assessment. Visual episodic memory was assessed using the Complex Figure Delayed Recall subtest from the Repeatable Battery for the Assessment of Neuropsychological Status (RBANS). Verbal episodic memory was assessed using Delayed Recall from the Free and Cued Selective Reminding Test (FCSRT). All participants underwent 3T MRI brain scanning with subsequent automatic measurement of the hemispheric hippocampal subfield volumes (CA1, CA2-CA3, CA4-dente gyrus, presubiculum, and subiculum). We used linear regressions to model the association between hippocampal subfield volumes and visual and verbal episodic memory tests while adjusting for age, sex, education, and total intracranial volume. ResultsParticipants had a mean age of 78.9 (SD=5.1) and 60.2% were female. Total hippocampal volume was associated with Complex Figure Delayed Recall (β=0.31, p=0.001) and FCSRT Delayed Recall (β=0.27, p=0.007); subiculum volume was associated with Complex Figure Delayed Recall (β=0.27, p=0.002) and FCSRT Delayed Recall (β=0.24, p=0.010); CA1 was associated with Complex Figure Delayed Recall (β=0.26, p<0.002) and FCSRT Delayed Recall (β=0.20, p=0.025). ConclusionsOur findings confirm previous research on the specific roles of CA1 and subiculum in episodic memory. Our results suggest that hippocampal subfields have sensitive roles in the process of visual and verbal episodic memory.

Episodic memory in depression: the unique contribution of the anterior caudate and hippocampus.

Learning and memory impairments in older adults with depression are linked to hippocampal atrophy. However, other subcortical regions may also be contributing to these deficits. We aimed to examine whether anterior caudate nucleus volume is significantly reduced in older adults with depression compared to controls; whether anterior caudate volume is associated with performance on tasks of episodic learning and memory, and if so, whether this association is independent of the effects of the hippocampus. Eighty-four health-seeking participants meeting criteria for lifetime major depressive disorder (mean age = 64.2, s.d. = 9.1 years) and 27 never-depressed control participants (mean age = 63.9, s.d. = 8.0 years) underwent neuropsychological assessment including verbal episodic memory tests [Rey Auditory Verbal Learning Test and Logical Memory (WMS-III)]. Magnetic resonance imaging was conducted, from which subregions of the caudate nucleus were manually demarcated bilaterally and hippocampal volume was calculated using semi-automated methods. Depressed subjects had smaller right anterior caudate (RAC) (t = 2.3, p = 0.026) and poorer memory compared to controls (t = 2.5, p < 0.001). For depressed subjects only, smaller RAC was associated with poorer verbal memory (r = 0.3, p = 0.003) and older age (r = -0.46, p < 0.001). Multivariable regression showed that the RAC and hippocampus volume uniquely accounted for 5% and 3% of the variance in memory, respectively (β = 0.25, t = 2.16, p = 0.033; β = 0.19, t = 1.71, p = 0.091). In older people with depression, the anterior caudate nucleus and the hippocampus play independent roles in mediating memory. While future studies examining this structure should include larger sample sizes and adjust for multiple comparisons, these findings support the critical role of the striatum in depression.

Longitudinal changes in odor identification performance and neuropsychological measures in aging individuals.

To examine changes in odor identification performance and cognitive measures in healthy aging individuals. While cross-sectional studies reveal associations between odor identification and measures of episodic memory, processing speed, and executive function, longitudinal studies so far have been ambiguous with regard to demonstrating that odor identification may be predictive of decline in cognitive function. One hundred and 7 healthy aging individuals (average age 60.2 years, 71% women) were assessed with an odor identification test and nonolfactory cognitive measures of verbal episodic memory, mental processing speed, executive function, and language 3 times, covering a period of 6.5 years. The cross-sectional results revealed odor identification performance to be associated with age, measures of verbal episodic memory, and processing speed. Using linear mixed models, the longitudinal analyses revealed age-associated decline in all measures. Controlling for retest effects, the analyses demonstrated that gender was a significant predictor for episodic memory and mental processing speed. Odor identification performance was further shown to be a significant predictor for episodic verbal memory. This study shows age-related decline in odor identification as well as nonolfactory cognitive measures. The finding showing that odor identification is a significant predictor for verbal episodic memory is of great clinical interest as odor identification has been suggested as a sensitive measure of incipient pathologic cognitive decline.

Cognitively impaired elderly exhibit insulin resistance and no memory improvement with infused insulin

Insulin resistance is a risk factor for Alzheimer's disease (AD), although its role in AD etiology is unclear. We assessed insulin resistance using fasting and insulin-stimulated measures in 51 elderly subjects with no dementia (ND; n = 37) and with cognitive impairment (CI; n = 14). CI subjects exhibited either mild CI or AD. Fasting insulin resistance was measured using the homeostatic model assessment of insulin resistance (HOMA-IR). Insulin-stimulated glucose disposal was assessed using the hyperinsulinemic-euglycemic clamp to calculate glucose disposal rate into lean mass, the primary site of insulin-stimulated glucose disposal. Because insulin crosses the blood-brain barrier, we also assessed whether insulin infusion would improve verbal episodic memory compared to baseline. Different but equivalent versions of cognitive tests were administered in counterbalanced order in the basal and insulin-stimulated state. Groups did not differ in age or body mass index. Cognitively impaired subjects exhibited greater insulin resistance as measured at fasting (HOMA-IR; ND: 1.09 [1.1] vs. CI: 2.01 [2.3], p = 0.028) and during the hyperinsulinemic clamp (glucose disposal rate into lean mass; ND: 9.9 (4.5) vs. AD 7.2 (3.2), p = 0.040). Cognitively impaired subjects also exhibited higher fasting insulin compared to ND subjects, (CI: 8.7 [7.8] vs. ND: 4.2 [3.8] μU/mL; p = 0.023) and higher fasting amylin (CI: 24.1 [39.1] vs. 8.37 [14.2]; p = 0.050) with no difference in fasting glucose. Insulin infusion elicited a detrimental effect on one test of verbal episodic memory (Free and Cued Selective Reminding Test) in both groups (p < 0.0001) and no change in performance on an additional task (delayed logical memory). In this study, although insulin resistance was observed in cognitively impaired subjects compared to ND controls, insulin infusion did not improve memory. Furthermore, a significant correlation between HOMA-IR and glucose disposal rate was present only in ND (p = 0.0002) but not in cognitively impaired (p = 0.884) subjects, indicating potentially important physiological differences between these cohorts.

Subjective cognitive impairment and Alzheimer's disease: a two year follow up of 51 subjects during two years

Subjective cognitive impairment (SCI) is defined by a state of subjective complaint, without objective cognitive deterioration. Amnestic mild cognitive impairment (A-MCI), which characterizes a syndrome between normal cognitive aging and early Alzheimer's disease (E-AD), is preceded by A-MCI from many years. SCI expresses a metacognitive impairment. A cohort of 51 subjects [7 normal controls (NC), 28 SCI, 12 A-MCI and 5 E-AD] was followed up during 24 months, with a neuropsychological evaluation each 6 months during 1 year (V1, V2, V3), then 1 year later (V4). Among the 28 SCI, 6 converted to A-MCI at V4 (21.42%), 1 to A-MCI-A at V3, then to E-AD at V4. These results suggest a continuum from SCI to A-MCI, and E-AD. Progressive SCI differed from non-progressive SCI on verbal episodic memory and executive functions tests at the initial examination. MRI showed anterior cingular atrophy in all SCI patients but hippocampal atrophy was only observed in 20 patients. Our results suggest that metacognition impairment is the expression of a dysfunction in the anterior pre-frontal cortex, in correlation with a syndrome of hyper-attention.

Computerised working-memory focused cognitive remediation therapy for psychosis — A preliminary study

BackgroundCognitive deficits are a core feature of schizophrenia and related psychotic disorders and are associated with decreased levels of functioning. Behavioural interventions have shown success in remediating these deficits; determining how best to maximise this benefit while minimising the cost is an important next step in optimising this intervention for clinical use. AimsTo examine the effects of a novel working-memory focused cognitive remediation (CR) training on cognitive difficulties based on internet delivery of training and weekly telephone support. MethodParticipants with a diagnosis of psychosis (n=56) underwent either 8weeks of CR (approximately 20h) or 8weeks of treatment as usual (TAU). General cognitive ability, working memory and episodic memory were measured both pre and post intervention for all participants. ResultsIn addition to improvements on trained working memory tasks, CR training was associated with significant improvements in two tests of verbal episodic memory. No association between CR and changes in general cognitive ability was observed. Effect sizes for statistically significant changes in memory were comparable to those reported in the literature based primarily on 1:1 training. ConclusionsThe cognitive benefits observed in this non-randomised preliminary study indicate that internet-based working memory training can be an effective cognitive remediation therapy. The successes and challenges of an internet-based treatment are discussed.