Worse Memory Performance Research Articles

The Impact of APOE ɛ4 in Alzheimer's Disease Differs According to Age.

We evaluated how the impact of apolipoprotein E4 (APOE4) differs according to age in Alzheimer's disease (AD) patients. We recruited 846 AD patients and 815 cognitively normal controls and categorized into three groups with respect to their age (<65, 65-74, and ≥75 years). We evaluated the risk of AD in APOE4 carriers and compared cortical thickness and cognitive function according to APOE4 status in each age group. At the point of this study, in young (<65 years) AD, APOE4 noncarriers had the most severe frontal and perisylvian atrophy, while in old (≥75 years) AD, APOE4 carriers had the most severe medial temporal atrophy. In AD under 75 years, APOE4 noncarriers and heterozygotes showed worse performance in language, visuospatial, and frontal function compared to homozygotes, while, in old (≥75 years) AD, APOE4 homozygotes showed worse performance in memory compared to noncarriers. As the detrimental effects of APOE4 seen in older AD patients were not found in younger AD patients, we suggest that some unrevealed factors are associated with cortical atrophy and non-amnestic cognitive dysfunction in young AD with APOE4 noncarriers.

Abstract TP417: Cortical Microinfarcts on 3T MRI in Cerebral Amyloid Angiopathy: Associations With MRI Burden and Cognitive Dysfunction

Background: Cerebral amyloid angiopathy (CAA) causes vascular cognitive impairment, possibly due to ischemic lesions that are caused by impaired cerebral blood flow. Cerebral microinfarcts (CMIs) are small ischemic lesions that are found in CAA patients at autopsy. Hypothesis: Cortical CMIs can be detected on in vivo 3T MR images in CAA and will correlate with markers of CAA-related vascular brain injury and cognitive function. Methods: We analysed data from CAA cases and neurologically healthy controls participating in the Functional Assessment of Vascular Reactivity (FAVR) study. All participants underwent a standardized clinical, neuropsychological and 3T MR assessment. Cortical CMIs were rated according to standardized criteria, by a single rater blinded to clinical information. Results: There were 36 CAA patients (mean age 73.0±9.0 years) and 22 healthy controls (69.0±8.3 years). Cortical CMIs were found in significantly more patients with CAA (50%) (median number: 1, range: 1-9) than in healthy controls (18%) ( p =0.02). In CAA, patients with cortical CMIs had higher white matter hyperintensity volumes (median 29.5 mL vs 13.0 mL, p =0.04) and cerebral microbleed counts (median 28 vs 5.5, p =0.049). CAA patients with cortical CMIs also showed lower occipital fMRI activation (median BOLD change 1.97% vs 2.57%, r =0.24, p =0.15) and worse memory performance (mean z -score -0.60 vs -0.05, p =0.12), although both effects were non-significant. No significant association of cortical CMIs with age, sex or vascular risk factors was found. Conclusions: Cortical CMIs are frequently detected on 3T MRI in CAA. They relate to well-established ischemic and hemorrhagic MRI markers of CAA. Therefore in vivo cortical CMIs can be regarded as a new marker of CAA disease severity. Additional, larger studies are needed to determine the relationship between CMI and clinical outcomes in CAA.

The DRD2 Taq1A A1 Allele May Magnify the Risk of Alzheimer's in Aging African-Americans.

Alzheimer's disease is an irreversible, progressive brain disorder that slowly destroys cognitive skills and the ability to perform the simplest tasks. More than 5 million Americans are afflicted with Alzheimer's; a disorder which ranks third, just behind heart disease and cancer, as a cause of death for older people. With no real cure and in spite of enormous efforts worldwide, the disease remains a mystery in terms of treatment. Importantly, African-Americans are two times as likely as Whites to develop late-onset Alzheimer's disease and less likely to receive timely diagnosis and treatment. Dopamine function is linked to normal cognition and memory and carriers of the DRD2 Taq1A A1 allele have significant loss of D2 receptor density in the brain. Recent research has shown that A1 carriers have worse memory performance during long-term memory (LTM) updating, compared to non-carriers or A2-carriers. A1carriers also show less blood oxygen level-dependent (BOLD) activation in the left caudate nucleus which is important for LTM updating. This latter effect was only seen in older adults, suggesting magnification of genetic effects on brain functioning in the elderly. Moreover, the frequency of the A1 allele is 0.40 in African-Americans, with an approximate prevalence of the DRD2 A1 allele in 50% of an African-American subset of individuals. This is higher than what is found in a non-screened American population (≤28%) for reward deficiency syndrome (RDS) behaviors. Based on DRD2 known genetic polymorphisms, we hypothesize that the DRD2 Taq1A A1 allele magnifies the risk of Alzheimer's in aging African-Americans. Research linking this high risk for Alzheimer's in the African-American population, with DRD2/ANKK1-TaqIA polymorphism and neurocognitive deficits related to LTM, could pave the way for novel, targeted pro-dopamine homeostatic treatment.

PATIENTS WITH SUBJECTIVE COGNITIVE DECLINE AND AMYLOID PATHOLOGY EXHIBIT SIGNIFICANT BRAIN ATROPHY, TAU PATHOLOGY AND MILD MEMORY DIFFICULTIES

To investigate whether amyloid pathology is associated with structural brain changes in cognitively normal (CN) participants with or without subjective cognitive decline (SCD). 303 cognitively normal and 173 participants with SCD between 60–87 years of age was included. Quantification of amyloid beta (Aβ) and tau in cerebrospinal fluid (CSF) was done using ELISA and brain atrophy on structural magnetic resonance images using Freesufer 5.3. Abnormal CSF Aβ42levels was used for classification of amyloid status. Aβ-pathology in cognitively normal subjects was not associated with brain atrophy, but with worse memory performance and increased levels of phosphorylated tau (P-tau) and total tau (Tau).However, patients with SCD, who exhibited Aβ-pathology, displayed significant atrophy in large areas of the brain including the bilateral dorsolateral prefrontal-, medial- and lateral temporal cortex, the left posterior cingulate and the right inferior parietal cortex, the bilateral hippocampus, thalamus and the left amygdala. Further, SCD cases with Aβ-pathology displayed increased levels of P-tau and Tau and poorer memory. SCD in combination with Aβ-pathology is a valid biomarker for preclinical AD with detectable neurodegeneration in the brain.

Maintenance of memory for melodies: Articulation or attentional refreshing?

Past research on the effects of articulatory suppression on working memory for nonverbal sounds has been characterized by discrepant findings, which suggests that multiple mechanisms may be involved in the rehearsal of nonverbal sounds. In two experiments we examined the potential roles of two theoretical mechanisms of verbal working memory-articulatory rehearsal and attentional refreshing-in the maintenance of memory for short melodies. In both experiments, participants performed a same-different melody comparison task. During an 8-s retention interval, interference tasks were introduced to suppress articulatory rehearsal, attentional refreshing, or both. In Experiment 1, only the conditions that featured articulatory suppression resulted in worse memory performance than in a control condition, and the suppression of both attentional refreshing and articulatory rehearsal concurrently did not impair memory more than articulatory suppression alone. Experiment 2 reproduced these findings and also confirmed that the locus of interference was articulatory and not auditory (i.e., the interference was not attributable to the sound of participants' own voices during articulatory suppression). Both experiments suggested that articulatory rehearsal played a role in the maintenance of melodies in memory, whereas attentional refreshing did not. We discuss potential theoretical implications regarding the mechanisms used for the rehearsal of nonverbal sounds in working memory.

The association between subjective memory complaint and objective cognitive function in older people with previous major depression.

The goal of this study is to investigate associations between subjective memory complaint and objective cognitive performance in older people with previous major depression–a high-risk sample for cognitive impairment and later dementia. A cross-sectional study was carried out in people aged 60 or over with previous major depression but not fulfilling current major depression criteria according to DSM-IV-TR. People with dementia or Mini-Mental State Examination score less than 17 were excluded. Subjective memory complaint was defined on the basis of a score ≧4 on the subscale of Geriatric Mental State schedule, a maximum score of 8. Older people aged equal or over 60 without any psychiatric diagnosis were enrolled as healthy controls. Cognitive function was evaluated using a series of cognitive tests assessing verbal memory, attention/speed, visuospatial function, verbal fluency, and cognitive flexibility in all participants. One hundred and thirteen older people with previous major depression and forty-six healthy controls were enrolled. Subjective memory complaint was present in more than half of the participants with depression history (55.8%). Among those with major depression history, subjective memory complaint was associated with lower total immediate recall and delayed verbal recall scores after adjustment. The associations between subjective memory complaint and worse memory performance were stronger in participants with lower depressive symptoms (Hamilton Depression Rating Scale score<7). The results suggest subjective memory complaint may be a valid appraisal of memory performance in older people with previous major depression and consideration should be given to more proactive assessment and follow-up in these clinical samples.

175.4 The Relationship of Aging and Inflammatory Biomarkers to Gray Matter Volume and Episodic Memory Performance in Schizophrenia: Evidence of Pathological Accelerated Aging

Abstract Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ. Therefore, we aim to evaluate the relationships of age, telomere length (TL) and CCL11 (aging and inflammatory biomarkers), and gray matter volumes (GM) to episodic memory performance in individuals with SZ compared to healthy controls (HC). 112 participants (48 SZ and 64 HC) underwent clinical and memory assessments, structural MRI, and had their peripheral blood drawn for biomarkers analysis. Comparisons of group means and correlations were performed. Participants with SZ had decreased TL and GM residual volume, increased CCL11, and worse memory performance compared to HC. In SZ, shorter TL was related to increased CCL11, and they were both related to reduced GM residual volume, all of which were related to worse memory performance. Older age was only associated with reduced GM, but longer duration of illness was related with all the aforementioned variables. Younger age of disease onset was related with increased CCL11 levels and worse memory performance. In HC, there were no significant correlations except for between memory and GM. Our results are consistent with accelerated aging in SZ. These results may indicate that it is not age itself, but the impact of the disease associated with a pathological accelerated aging that leads to impaired outcomes in SZ.Akira Sawa, johns Hopkins University, Johns Hopkins Hospital and Medical Institutions

Telomere Length and CCL11 Levels are Associated With Gray Matter Volume and Episodic Memory Performance in Schizophrenia: Evidence of Pathological Accelerated Aging.

Schizophrenia (SZ) is associated with increased somatic morbidity and mortality, in addition to cognitive impairments similar to those seen in normal aging, which may suggest that pathological accelerated aging occurs in SZ. Therefore, we aim to evaluate the relationships of age, telomere length (TL), and CCL11 (aging and inflammatory biomarkers, respectively), gray matter (GM) volume and episodic memory performance in individuals with SZ compared to healthy controls (HC). One hundred twelve participants (48 SZ and 64 HC) underwent clinical and memory assessments, structural MRI, and had their peripheral blood drawn for biomarkers analysis. Comparisons of group means and correlations were performed. Participants with SZ had decreased TL and GM volume, increased CCL11, and worse memory performance compared to HC. In SZ, shorter TL was related to increased CCL11, and both biomarkers were related to reduced GM volume, all of which were related to worse memory performance. Older age was only associated with reduced GM, but longer duration of illness was related with all the aforementioned variables. Younger age of disease onset was associated with increased CCL11 levels and worse memory performance. In HC, there were no significant correlations except between memory and GM. Our results are consistent with the hypothesis of accelerated aging in SZ. These results may indicate that it is not age itself, but the impact of the disease associated with a pathological accelerated aging that leads to impaired outcomes in SZ.

Tau and β-Amyloid Are Associated with Medial Temporal Lobe Structure, Function, and Memory Encoding in Normal Aging.

Normal aging is associated with a decline in episodic memory and also with aggregation of the β-amyloid (Aβ) and tau proteins and atrophy of medial temporal lobe (MTL) structures crucial to memory formation. Although some evidence suggests that Aβ is associated with aberrant neural activity, the relationships among these two aggregated proteins, neural function, and brain structure are poorly understood. Using in vivo human Aβ and tau imaging, we demonstrate that increased Aβ and tau are both associated with aberrant fMRI activity in the MTL during memory encoding in cognitively normal older adults. This pathological neural activity was in turn associated with worse memory performance and atrophy within the MTL. A mediation analysis revealed that the relationship with regional atrophy was explained by MTL tau. These findings broaden the concept of cognitive aging to include evidence of Alzheimer's disease-related protein aggregation as an underlying mechanism of age-related memory impairment.SIGNIFICANCE STATEMENT Alterations in episodic memory and the accumulation of Alzheimer's pathology are common in cognitively normal older adults. However, evidence of pathological effects on episodic memory has largely been limited to β-amyloid (Aβ). Because Aβ and tau often cooccur in older adults, previous research offers an incomplete understanding of the relationship between pathology and episodic memory. With the recent development of in vivo tau PET radiotracers, we show that Aβ and tau are associated with different aspects of memory encoding, leading to aberrant neural activity that is behaviorally detrimental. In addition, our results provide evidence linking Aβ- and tau-associated neural dysfunction to brain atrophy.

Effects of GRASP variation on memory in psychiatrically healthy individuals and cognitive dysfunction in schizophrenics

Mechanistic studies indicate general receptor for phosphoinositides-1-associated scaffold protein (GRASP, also referred to as Tamalin) is involved in neurite development, proliferation, and branching in hippocampal neurons, but its physiological effects on cognitive function is mostly unknown. Cognitive impairment is a core feature of schizophrenia, and recent reports indicate increased abundance of GRASP proteins in postmortem schizophrenia cortex and hippocampus, both of these structures being highly relevant to cognitive processes. We therefore assessed the effects of a single nucleotide polymorphism (SNP) rs10876227 [G>A] in GRASP on eight different domains of cognitive function in a well-established Caucasian case-control cohort for schizophrenia. In 261 control individuals (166 males), strong effects of rs10876227 were observed on immediate memory, delayed memory, and working memory, with the major G allele associated with worse memory performance on each test. Additional analyses including 249 patients with schizophrenia (174 males) indicated that the G allele of rs10876227 was also able to distinguish male schizophrenia participants with severe cognitive deficits (CD; 81 males) from male schizophrenia participants with relatively spared cognitive function (CS; 91 males). However analyses of the effects of GRASP variation on individual cognitive domains in the combined sample showed no interactive effects of clinical status and rs10876227 variation. These findings converge with prior mechanistic and postmortem studies to strongly support contribution of GRASP variation to memory function, and general cognitive ability in men with schizophrenia, likely via GRASP-directed plasticity. The implications of these findings extend to other disorders where cognitive function is a core component, such as dementia, autism and mental retardation.

War and remembrance: Combat exposure in young adulthood and memory function sixty years later

ObjectiveIdentifying adaptive ways to cope with extreme stress is essential to promoting long-term health. Memory systems are highly sensitive to stress, and combat exposure during war has been shown to have deleterious effects on cognitive processes, such as memory, decades later. No studies have examined coping styles used by combat veterans and associations with later-life cognitive functioning. Defenses are coping mechanisms that manage difficult memories and feelings, with some more closely related to memory processes (e.g., suppression, repression). Utilizing a longitudinal database, we assessed how reliance on certain defense mechanisms after World War II combat exposure could affect cognitive health 60years later. MethodData spanning 75years were available on 71 men who had post-war assessment of combat exposure, defense mechanism ratings (ages 19–50), and late-life neuropsychological testing. Interaction models of combat exposure with defenses predicting late-life memory were examined. ResultsIn bivariate analyses, greater reliance on suppression correlated with worse memory performance (r=−0.30, p=.01), but greater reliance on repression did not. Greater reliance on suppression strengthened the link between combat exposure and worse memory in late life (R2=0.24, p<.001). In contrast, greater reliance on repression attenuated the link between combat exposure and poorer late-life memory (R2=0.19, p<.001). ConclusionsResults suggest that coping styles may affect the relationship between early-adult stress and late-life cognition. Findings highlight the importance of understanding how coping styles may impact cognitive functioning as people move through adult life.

BDNF Val66Met moderates memory impairment, hippocampal function and tau in preclinical autosomal dominant Alzheimer's disease.

SEE ROGAEVA AND SCHMITT-ULMS DOI101093/AWW201 FOR A SCIENTIFIC COMMENTARY ON THIS ARTICLE: The brain-derived neurotrophic factor (BDNF) Val66Met polymorphism is implicated in synaptic excitation and neuronal integrity, and has previously been shown to moderate amyloid-β-related memory decline and hippocampal atrophy in preclinical sporadic Alzheimer's disease. However, the effect of BDNF in autosomal dominant Alzheimer's disease is unknown. We aimed to determine the effect of BDNF Val66Met on cognitive function, hippocampal function, tau and amyloid-β in preclinical autosomal dominant Alzheimer's disease. We explored effects of apolipoprotein E (APOE) ε4 on these relationships. The Dominantly Inherited Alzheimer Network conducted clinical, neuropsychological, genetic, biomarker and neuroimaging measures at baseline in 131 mutation non-carriers and 143 preclinical autosomal dominant Alzheimer's disease mutation carriers on average 12 years before clinical symptom onset. BDNF genotype data were obtained for mutation carriers (95 Val66 homozygotes, 48 Met66 carriers). Among preclinical mutation carriers, Met66 carriers had worse memory performance, lower hippocampal glucose metabolism and increased levels of cerebrospinal fluid tau and phosphorylated tau (p-tau) than Val66 homozygotes. Cortical amyloid-β and cerebrospinal fluid amyloid-β42 levels were significantly different from non-carriers but did not differ between preclinical mutation carrier Val66 homozygotes and Met66 carriers. There was an effect of APOE on amyloid-β levels, but not cognitive function, glucose metabolism or tau. As in sporadic Alzheimer's disease, the deleterious effects of amyloid-β on memory, hippocampal function, and tau in preclinical autosomal dominant Alzheimer's disease mutation carriers are greater in Met66 carriers. To date, this is the only genetic factor found to moderate downstream effects of amyloid-β in autosomal dominant Alzheimer's disease.

Levels of tau protein in plasma are associated with neurodegeneration and cognitive function in a population-based elderly cohort

IntroductionTau protein levels in plasma may be a marker of neuronal damage. We examined associations between plasma tau levels and Alzheimer's disease (AD)–related magnetic resonance imaging (MRI) and positron emission tomography (PET) neuroimaging measures among nondemented individuals. MethodsParticipants included 378 cognitively normal (CN) and 161 mild cognitive impairment (MCI) individuals enrolled in the Mayo Clinic Study of Aging with concurrent neuropsychological measures and amyloid PET, fluorodeoxyglucose PET, and MRI. Baseline plasma tau levels were measured using the Quanterix Simoa-HD1 tau assay. ResultsPlasma tau levels were higher in MCI compared with CN (4.34 vs. 4.14 pg/mL, P = .078). In regression models adjusted for age, gender, education, and APOE, higher plasma tau was associated with worse memory performance (b = −0.30, P = .02) and abnormal cortical thickness in an AD signature region (odds ratio = 1.80, P = .018). DiscussionPlasma tau is associated with cortical thickness and memory performance. Longitudinal studies will better elucidate the associations between plasma tau, neurodegeneration, and cognition.

RISK FACTORS ASSOCIATED WITH DECREASED CORTICAL THICKNESS IN DEMENTIA FREE OKINAWAN ELDERY

Cortical gray matter (GM) decline is a hallmark of neurodegenerative disease; however, its etiology and implication in dementia-free aging is unclear. The aims of this study were to: 1) investigate the impact of cortical thickness on cognition, and, 2) examine systemic inflammation and cerebrovascular disease (CVD) as potential risk factors for GM degeneration. 91 dementia-free Okinawan participants (mean age 83.6) from the Keys to Optimal Cognitive Aging (KOCOA) Project underwent MRI, cognitive, and physical evaluation. Mean cortical thickness (MCT) was derived using FreeSurfer. Serum markers of inflammation and CVD risk were obtained. CVD risk status was calculated based on >2 of the following: ever smoked, glycosylated hemoglobin >5.6, systolic blood pressure > 139, taking anti-hypertension medication, serum triglyceride >150, and high density lipoprotein < 40 in men, or < 50 in women. Inflammatory markers included: interleukin-6 (IL6) and high-sensitivity C-reactive protein (hsCRP). Subjects were surveyed regarding physical activities (PA), including walking and yoga. Multivariate analyses examined relationships between MCT and memory (mini mental word recall) and executive function (verbal fluency). Spearman’s rank order correlation or t-tests examined the relationships between MCT and: age, PA, CVD risk, and inflammatory markers. Voxel based morphometry (VBM) examined relationships between regional GM density and factors significant in the previous univariate analysis. Exploratory analyses examined systemic inflammation in relation to PA. After adjusting for age, gender, and %hippo volume, decreased MCT was associated with worse memory, but not executive function. In univariate analyses, decreased MCT was associated with increased IL6 (0.04), but not with age, PA, hsCRP or CVD risk. VBM analysis demonstrated greater IL6 to be associated with decreased cortical density in the inferior and middle temporal cortex, bilaterally. After adjusting for age and gender, greater yoga participation (p = 0.02), but not walking, was associated with lower IL6 levels. Decreased MCT is associated with worse memory performance in dementia free-Okinawans. Greater IL6 was related to decreased temporal lobe cortical thickness, and decreased PA. Low-impact stretch activities, such as yoga, should be further explored as potential ways to decrease systemic inflammation and prevent cortical thinning and memory loss in older individuals. VBM analysis with threshold-free cluster enhancement and permutation testing to correct for multiple comparisons. Colored voxels indicate regions of decreased GM density significantly associated with higher IL6, age and gender adjusted. Serum IL6 in relation to yoga frequency (p = 0.02 in final model adjusted for age and gender).

IMPACT OF CO-MORBID AMYLOID PATHOLOGY ON CLINICAL PHENOTYPE OF PATIENTS WITH VASCULAR COGNITIVE DISORDERS

Cerebrovascular disease is an important cause of cognitive impairment and dementia, and vascular cognitive disorders (VCD) are conceptually distinct from Alzheimer's disease (AD). However, cerebrovascular and amyloid pathology may be co-morbid, particularly in older patients. Amyloid-beta biomarkers can detect amyloid pathology in vivo. Our aim was to investigate the impact of co-morbid amyloid pathology on the clinical phenotype of patients with VCD. From the Amsterdam Dementia Cohort we included 218 patients with VCD who fulfilled the 2014 VASCOG criteria (66 with Major VCD and 152 with Mild VCD). As a reference group we included 120 patients with (prodromal) AD (85 with MCI and 35 with dementia due to AD). All subjects underwent a diagnostic work-up including brain MRI and lumbar puncture. We defined presence of amyloid pathology (A+) as CSF Abeta-42 <638ng/L. VCD patients were termed V+, patients in the reference group V-. This resulted in 116 A+V+, 102 A-V+, and 120 A+V- patients. We used linear regression analysis to compare MMSE scores, z-scores for neuropsychological test performance in five cognitive domains, and scores on the neuropsychiatric inventory (NPI), adjusting for age, sex and education. The table gives the subject characteristics according to study group. Amyloid-negative VCD patients were younger than those who were amyloid-positive. Mean MMSE scores did not differ between study groups. The figure shows the association of VCD diagnosis and amyloid status with neuropsychological test performance. Greatest memory impairment was found in the A+V- group (p<0.05). In VCD patients (V+), co-morbid amyloid-positivity was associated with worse memory performance (A+V+ < A-V+, p<0.05). Conversely, amyloid-negative VCD patients had greater attentional and executive deficits (A-V+ < A+V+, p<0.05), as well as higher NPI scores (A-V+ [15.3±14.0] > A+V+ [9.8±10.5]; p<0.05). The association of VCD diagnosis and amyloid status with neuropsychological test performance.

Diffusion tensor imaging of the hippocampus in chronic cigarette smokers

PurposePrevious studies have demonstrated neuronal dis-integrity in chronic smokers using diffusion tensor imaging (DTI). However, assessment of hippocampal DTI has not been performed in this group. The purpose of this study was to investigate the hippocampal integrity in chronic smokers and non-smokers and to compare this to memory performance. MethodsWe used in vivo DTI to measure the differences in hippocampal integrity between 88 chronic smoker and 88 non-smoking subjects. DTI was performed on a 3T scanner. We administered a verbal learning test to assess new verbal learning capabilities. The immediate recall (IR) was administered immediately after test procedure and delayed recall (DR) after 15min. ResultsMean values of fractional anisotropy (FA) for non-smokers and smokers were 0.46 and 0.40, respectively (p<0.05). Mean IR word number for non-smokers and smokers was 11.6, 9.04, respectively (p<0.05). The mean word number of DR for non-smokers and smokers was 10.2, 7.2, respectively (p<0.05). ConclusionsThis is the first study of hippocampal DTI assessment in the chronic smokers. We found that decreased hippocampal FA associated with neuronal dis-integrity and worse memory performance in chronic smokers than non-smokers. We also found a low positive correlation hippocampal FA values with memory performance in nonsmoking group

Prefrontal contributions to relational encoding in amnestic mild cognitive impairment

Relational memory declines are well documented as an early marker for amnestic mild cognitive impairment (aMCI). Episodic memory formation relies on relational processing supported by two mnemonic mechanisms, generation and binding. Neuroimaging studies using functional magnetic resonance imaging (fMRI) have primarily focused on binding deficits which are thought to be mediated by medial temporal lobe dysfunction. In this study, prefrontal contributions to relational encoding were also investigated using fMRI by parametrically manipulating generation demands during the encoding of word triads. Participants diagnosed with aMCI and healthy control subjects encoded word triads consisting of a category word with either, zero, one, or two semantically related exemplars. As the need to generate increased (i.e., two- to one- to zero-link triads), both groups recruited a core set of regions associated with the encoding of word triads including the parahippocampal gyrus, superior temporal gyrus, and superior parietal lobule. Participants diagnosed with aMCI also parametrically recruited several frontal regions including the inferior frontal gyrus and middle frontal gyrus as the need to generate increased, whereas the control participants did not show this modulation. While there is some functional overlap in regions recruited by generation demands between the groups, the recruitment of frontal regions in the aMCI participants coincides with worse memory performance, likely representing a form of neural inefficiency associated with Alzheimer's disease.

Hippocampal volume and verbal memory performance in late-stage bipolar disorder

Studies about changes in hippocampal volumes in subjects with bipolar disorder (BD) have been contradictory. Since the number of manic episodes and hospitalization has been associated with brain changes and poor cognitive outcomes among BD patients, we have hypothesized that these variables could clarify this issue. We stratified subjects with BD in early (BD-Early), intermediate (BD-intermediate) and late (BD-Late) stages as a function of number of manic episodes and prior hospitalization. Then, we compared their hippocampal volumes and California Verbal Learning Test-II (CVLT-II) scores with healthy controls (HC) using the general linear model. A total of 173 subjects were included in the study (112 HC, 15 BD-Early, 30 BD-Intermediate, and 16 BD-Late). We found a significant group effect on hippocampus volume (F(3,167) = 3.227, p = 0.024). Post-hoc analysis showed that BD-Late subjects had smaller hippocampus than HC (p = 0.017). BD-Early and BD-Intermediate subjects showed no significant difference in hippocampus volume compared to HC and BD-Late subjects. The CVLT trial 1 to 5 scores were significantly different across the groups (F(3,167) = 6.371, p < 0.001). Post-hoc analysis showed that BD-Intermediate (p = 0.006) and BD-Late (p = 0.017) subjects had worse memory performance during immediate recall than HC, while the performance difference between BD-Early subjects and HC was not significant (p = 0.208). These findings add to the notion that BD is a neuroprogressive disorder with brain changes and cognitive impairment according to prior morbidity (number of manic episodes and hospitalization). Also, they suggest that hippocampus is a brain marker and a potential therapeutic target for patients at late stage.

Memory impairment in multiple sclerosis: Relevance of hippocampal activation and hippocampal connectivity

Background: Memory impairment is frequent in multiple sclerosis (MS), but it is unclear what functional brain changes underlie this cognitive deterioration. Objective: To investigate functional hippocampal activation and connectivity, in relation to memory performance in MS. Methods: Structural and functional magnetic resonance imaging data were acquired for 57 MS patients and 28 healthy controls (HCs), yielding hippocampal measures of volume, lesions, functional activation during a memory task and functional connectivity at rest. Memory function was based on two subtests of a larger neuropsychological test battery and related to hippocampal neuroimaging measures, using linear regression. Results: Hippocampal volume was lower in MS patients, as compared to HCs. In MS, hippocampal activation during the task was increased in cognitively preserved, but decreased in cognitively impaired, patients. Increased hippocampal connectivity was detected in MS patients, as compared to HCs, between the left hippocampus and the right posterior cingulate. Memory impairment in MS was explained (adjusted R2 = 0.27) by male gender, decreased hippocampal activation and increased hippocampal connectivity (p = 0.001). Conclusions: Decreased activation of the hippocampus, increased connectivity and male gender were associated with worse memory performance in MS. These results indicate that increased activation and increased connectivity do not always coincide, and relate differently to cognitive dysfunction in MS.

The effect of repetition in Internet banner ads and the moderating role of animation

Many advertising repetition studies have demonstrated wear-out effects, and found several moderating variables. In the context of Internet banner ads, this study examines the effects of repetition on attention, memory, and attitude, and identifies the moderating role of animation. By analyzing data on users’ actual visual attention, we found attention wear-out occurs with static but not with animated banner ads, which consequently influences the downstream effects: Compared to a static banner ad, an animated ad barely attracts consumers’ attention initially, resulting in worse memory performance and attitude in the beginning. However, with repeated brief exposures, animated banner ads eventually catch up with the static ads on memory and generate even better performance in terms of attitude. To summarize, animations signal the users the existence of ads and lead to ad avoidance behavior, but after repetitive exposures they induce positive user attitude through the mere exposure effect. Both the theoretical and practical implications are explored for using animation on the banner ads.