Decline In Visual Memory Research Articles

Early cerebral amyloid-β accumulation and hypermetabolism are associated with subtle cognitive deficits before accelerated cerebral atrophy

AimsAlzheimer’s disease (AD) is characterized by the accumulation of amyloid beta (Aβ) in the brain. The deposition of Aβ is believed to initiate a detrimental cascade, including cerebral hypometabolism, accelerated brain atrophy, and cognitive problems—ultimately resulting in AD. However, the timing and causality of the cascade resulting in AD are not yet fully established. Therefore, we examined whether early Aβ accumulation affects cerebral glucose metabolism, atrophy rate, and age-related cognitive decline before the onset of neurodegenerative disease.MethodsParticipants from the Metropolit 1953 Danish Male Birth Cohort underwent brain positron emission tomography (PET) imaging using the radiotracers [11C]Pittsburgh Compound-B (PiB) (N = 70) and [18F]Fluorodeoxyglucose (FDG) (N = 76) to assess cerebral Aβ accumulation and glucose metabolism, respectively. The atrophy rate was calculated from anatomical magnetic resonance imaging (MRI) scans conducted presently and 10 years ago. Cognitive decline was examined from neurophysiological tests conducted presently and ten or 5 years ago.ResultsHigher Aβ accumulation in AD-critical brain regions correlated with greater visual memory decline (p = 0.023). Aβ accumulation did not correlate with brain atrophy rates. Increased cerebral glucose metabolism in AD-susceptible regions correlated with worse verbal memory performance (p = 0.040).ConclusionsAβ accumulation in known AD-related areas was associated with subtle cognitive deficits. The association was observed before hypometabolism or accelerated brain atrophy, suggesting that Aβ accumulation is involved early in age-related cognitive dysfunction. The association between hypermetabolism and worse memory performance may be due to early compensatory mechanisms adapting for malfunctioning neurons by increasing metabolism.

Network Connectivity Alterations across the MAPT Mutation Clinical Spectrum.

Microtubule-associated protein tau (MAPT) mutations cause frontotemporal lobar degeneration, and novel biomarkers are urgently needed for early disease detection. We used task-free functional magnetic resonance imaging (fMRI) mapping, a promising biomarker, to analyze network connectivity in symptomatic and presymptomatic MAPT mutation carriers. We compared cross-sectional fMRI data between 17 symptomatic and 39 presymptomatic carriers and 81 controls with (1) seed-based analyses to examine connectivity within networks associated with the 4 most common MAPT-associated clinical syndromes (ie, salience, corticobasal syndrome, progressive supranuclear palsy syndrome, and default mode networks) and (2) whole-brain connectivity analyses. We applied K-means clustering to explore connectivity heterogeneity in presymptomatic carriers at baseline. Neuropsychological measures, plasma neurofilament light chain, and gray matter volume were compared at baseline and longitudinally between the presymptomatic subgroups defined by their baseline whole-brain connectivity profiles. Symptomatic and presymptomatic carriers had connectivity disruptions within MAPT-syndromic networks. Compared to controls, presymptomatic carriers showed regions of connectivity alterations with age. Two presymptomatic subgroups were identified by clustering analysis, exhibiting predominantly either whole-brain hypoconnectivity or hyperconnectivity at baseline. At baseline, these two presymptomatic subgroups did not differ in neuropsychological measures, although the hypoconnectivity subgroup had greater plasma neurofilament light chain levels than controls. Longitudinally, both subgroups showed visual memory decline (vs controls), yet the subgroup with baseline hypoconnectivity also had worsening verbal memory and neuropsychiatric symptoms, and extensive bilateral mesial temporal gray matter decline. Network connectivity alterations arise as early as the presymptomatic phase. Future studies will determine whether presymptomatic carriers' baseline connectivity profiles predict symptomatic conversion. ANN NEUROL 2023;94:632-646.

The cognitive impairments of electroconvulsive therapy

IntroductionElectroconvulsive therapy (ECT) is one of the most controversial treatments in medicine, mainly because of its still unknown mechanism of action and uncertainty about cognitive side effects. ECT is used mainly when antidepressant medications do not result in an adequate response in severe depression, and may also be indicated for other disorders. During the acute phase after electroconvulsive therapy there are better cognitive outcomes with unilateral ECT compared to bilateral ECT.ObjectivesThis literature review aims to analyze the validity of electroconvulsive therapy despite the cognitive impairment and effectiveness of electroconvulsive therapy.MethodsThe method used was a literary review based on articles published in Scielo and Pubmed. Eighteen electronic articles in English were used in a 10-year time frame, using the term electroconvulsive therapy as descriptors in the title, as well as cognitive impairment in all fields.ResultsWe observed that older individuals benefit the most from ECT, with faster response rates and higher remission rates in rapid responders, on the other hand they have a higher risk of cognitive side effects induced by electroconvulsive therapy. Anterograde and retrograde amnesia usually resolve within months. Recovery from retrograde amnesia may be incomplete, resulting in permanent amnesia for events that occurred close to the time of ECT. Right-sided or bilateral electroconvulsive therapy was more effective in treating depression than left-sided. Patients who used right unilateral electroconvulsive therapy had less impairment of verbal memory and post-ictal recovery and faster reorientation compared to left unilateral and bilateral, whereas left unilateral ECT showed a smaller decline in visual memory and non-verbal tests. Bilateral ECT is more effective and faster acting, but is associated with more cognitive impairments compared to unilateral ECT.ConclusionsWe can conclude that ECT is an effective, safe and tolerable treatment, which results in faster and higher remission rates compared to treatment alone with pharmacotherapy. Cognitive effects are largely transient, usually ending within three months. The decision to use unilateral right, left, or bilateral ECT should be made individually for the patient and should be based on a careful assessment of the relative priorities of efficacy versus minimizing cognitive impairment.Disclosure of InterestNone Declared

Longitudinal trajectories in clinical progression of Alzheimer’s disease tau positron emission tomography subtypes

AbstractBackgroundRecent evidence suggests substantial heterogeneity in Alzheimer's disease (AD). Distinct subtypes have been identified using tau pet positron emissions tomography. There is only limited knowledge about the longitudinal cognitive and clinical trajectories of these subtypes.MethodThree hundred and twenty‐one participants were included with 155 amyloid‐β (Aβ) negative and cognitively normal healthy controls (HC, 74 years, 85 female) and 166 Aβ positive patients with mild cognitive impairment or AD dementia (Alzheimer’s disease spectrum, ADS, 75 years, 76 female). We identified distinct subtypes using an unbiased, data‐driven and similarity‐based Louvain clustering algorithm, modified using a consensus method. Longitudinal trajectories in cognitive domain scores and clinical severity were compared between tau subtypes using mixed effect models.ResultFour distinct tau PET imaging subtypes were identified, including a posterior, a limbic, a medio‐temoral lobe (MTL) sparing and a temporal subtype (Figure 1). In longitudinal analyses, the subtypes differed substantially in disease progression in the different cognitive domains, i.e. episodic memory, executive functioning, language and visual memory. The temporal subtype showed the steepest decline in visual memory and language, the medial temporal lobe sparing subtype showed only minor language degradation and the limbic subtype showed relatively preserved executive functioning but decline in all other cognitive domains. The MTLs was by far worst affected by clinical progression. The remaining subtypes showed only slight deterioration in clinical severity (Figure 2).ConclusionOur results suggest characteristic differences in longitudinal cognitive and clinical trajectories of the tau PET imaging subtypes. Analyzing the heterogeneity in AD using tau PET spatial distribution patterns, significantly improves our understanding of the biological underpinnings of individual differences in clinical presentation and progression. An in‐depth understanding of the subtype’s characteristics in the longitudinal trajectories contributes significantly to improved prevention strategies and individualized precision treatments.

Preliminary findings of accelerated visual memory decline and baseline brain correlates in middle-age and older adults with autism: The case for hippocampal free-water.

Research aimed at understanding cognitive and brain aging in adults with autism spectrum disorder (ASD) is growing, but critical longitudinal work is scant. Adults with ASD struggle with tasks involving visual memory compared with neurotypical adults (NT). This may be related to differences in size or integrity of the hippocampus and its' primary structural connectivity pathway, the fornix. The aim of this study was to describe preliminary findings of longitudinal aging trajectories in short- and long-term visual memory abilities in middle-age and older adults with ASD, compared with matched NT adults. We then evaluated baseline multi-modal imaging metrics of the hippocampal system, including the relatively novel metric of free-water, as potential correlates of longitudinal memory change in the ASD group. Middle-age and older adults with ASD (n = 25) and matched NT adults (n = 25) between the ages of 40 and 70 years were followed longitudinally at ~2-year intervals (range 2-5 years). Participants completed the Wechsler Memory Scale III Visual Reproduction task. Longitudinal mixed models were utilized to detect group differences in memory change with baseline age and sex as covariates. Hippocampal volume was measured via T1-weighted MRI images with FreeSurfer. Fornix fractional anisotropy and hippocampal and fornix free-water were measured from diffusion tensor imaging scans. Exploratory correlations were run between individual hippocampal system metrics and longitudinal slopes of visual memory change. There was a significant group by time interaction for long-term visual memory, such that middle-age and older adults with ASD declined faster than matched NT adults. There was no group by time interaction for short-term visual memory. Baseline hippocampal free-water was the only hippocampal system metric that correlated with long-term visual memory change in the ASD group. As one of the first longitudinal cognitive and brain aging studies in middle-age and older adults with ASD, our findings suggest vulnerabilities for accelerated long-term visual memory decline, compared to matched NT adults. Further, baseline hippocampal free-water may be a predictor of visual memory change in middle-age and older adults with ASD. These preliminary findings lay the groundwork for future prognostic applications of MRI for cognitive aging in middle-age and older adults with ASD.

Optimal Surgical Extent for Memory and Seizure Outcome in Temporal Lobe Epilepsy.

ObjectivePostoperative memory decline is an important consequence of anterior temporal lobe resection (ATLR) for temporal lobe epilepsy (TLE), and the extent of resection may be a modifiable factor. This study aimed to define optimal resection margins for cognitive outcome while maintaining a high rate of postoperative seizure freedom.MethodsThis cohort study evaluated the resection extent on postoperative structural MRI using automated voxel‐based methods and manual measurements in 142 consecutive patients with unilateral drug refractory TLE (74 left, 68 right TLE) who underwent standard ATLR.ResultsVoxel‐wise analyses revealed that postsurgical verbal memory decline correlated with resections of the posterior hippocampus and inferior temporal gyrus, whereas larger resections of the fusiform gyrus were associated with worsening of visual memory in left TLE. Limiting the posterior extent of left hippocampal resection to 55% reduced the odds of significant postoperative verbal memory decline by a factor of 8.1 (95% CI 1.5–44.4, p = 0.02). Seizure freedom was not related to posterior resection extent, but to the piriform cortex removal after left ATLR. In right TLE, variability of the posterior extent of resection was not associated with verbal and visual memory decline or seizures after surgery.InterpretationThe extent of surgical resection is an independent and modifiable risk factor for cognitive decline and seizures after left ATLR. Adapting the posterior extent of left ATLR might optimize postoperative outcome, with reduced risk of memory impairment while maintaining comparable seizure‐freedom rates. The current, more lenient, approach might be appropriate for right ATLR. ANN NEUROL 2022;91:131–144

High Glycemic Load Is Associated with Cognitive Decline in Apolipoprotein E ε4 Allele Carriers.

Recent evidence suggests that a high glycemic load (GL) diet is a risk factor for dementia, especially among apolipoprotein E ε4 allele (APOE4) carriers, while its association with cognitive decline is poorly known. Here, we investigated the association of high-GL meals with cognitive decline in older adults during a 12-year follow-up, according to their APOE4 carrier status. We used random-effect models and data from 2539 elderly participants from the Three-City study who completed a food frequency questionnaire (FFQ) to longitudinally assess the association of GL with changes in different cognitive domains (verbal fluency, visual memory, attention, visual motor processing speed, episodic memory). In APOE4 carriers, afternoon snack with high GL was significantly associated with cognitive decline in visual memory, episodic memory, and global cognition compared with APOE4 non-carriers. This study suggests a detrimental association between a high-GL diet and cognitive decline. The promotion of a low GL diet as a target to prevent cognitive decline in high-risk populations deserves more research.

The association of cognitive phenotypes with postoperative outcomes after epilepsy surgery in patients with temporal lobe epilepsy

IntroductionThe concept of cognitive phenotypes has been developed to categorize the heterogeneity of neuropsychological profiles in patients with temporal lobe epilepsy (TLE). This study examines the utility of cognitive phenotypes derived from clinical criteria in the prediction of postoperative outcomes. MethodsScores from 9 standardized neuropsychological tests were used to sample preoperative performance in 4 core domains (intellectual, memory, language, & executive function) in 445 patients with TLE (206 right: 236 left). Patients were grouped into 3 clinical phenotypes using clinical criteria: 1. intact cognition, 2. isolated memory and/or language impairment, and 3. widespread impairment. Patients who did not meet the criteria for these phenotypes were characterized as having a mixed profile phenotype. ResultsApproximately half of the sample had intact cognitive function, with one-quarter demonstrating isolated impairments in language and memory function. The remainder demonstrated widespread impairment or a mixed pattern of cognitive impairments. The clinically derived cognitive phenotypes were associated with demographic and clinical characteristics. Patients with widespread cognitive impairments had an earlier onset of seizures than those with other cognitive phenotypes. They also reported higher levels of depression. Higher levels of anxiety were reported in those with isolated memory/language impairments. Phenotypes were not associated with postoperative seizure outcome or postoperative declines in verbal memory or language function, but an intact phenotype was associated with a greater risk of decline in visual learning than right-sided surgery. ConclusionsDistinct cognitive phenotypes in TLE can be identified using clinical criteria and may reflect neurodevelopmental influences and mood in addition to progression of the disease. Phenotype may be a more powerful predictor of postoperative decline in visual memory than laterality of surgery.

Hippocampal Shape Is Associated with Memory Deficits in Temporal Lobe Epilepsy.

ObjectiveCognitive problems, especially disturbances in episodic memory, and hippocampal sclerosis are common in temporal lobe epilepsy (TLE), but little is known about the relationship of hippocampal morphology with memory. We aimed to relate hippocampal surface‐shape patterns to verbal and visual learning.MethodsWe analyzed hippocampal surface shapes on high‐resolution magnetic resonance images and the Adult Memory and Information Processing Battery in 145 unilateral refractory TLE patients undergoing epilepsy surgery, a validation set of 55 unilateral refractory TLE patients, and 39 age‐ and sex‐matched healthy volunteers.ResultsBoth left TLE (LTLE) and right TLE (RTLE) patients had lower verbal (LTLE 44 ± 11; RTLE 45 ± 10) and visual learning (LTLE 34 ± 8, RTLE 30 ± 8) scores than healthy controls (verbal 58 ± 8, visual 39 ± 6; p < 0.001). Verbal learning was more impaired the greater the atrophy of the left superolateral hippocampal head. In contrast, visual memory was worse with greater bilateral inferomedial hippocampal atrophy. Postsurgical verbal memory decline was more common in LTLE than in RTLE (reliable change index in LTLE 27% vs RTLE 7%, p = 0.006), whereas there were no differences in postsurgical visual memory decline between those groups. Preoperative atrophy of the left hippocampal tail predicted postsurgical verbal memory decline.InterpretationMemory deficits in TLE are associated with specific morphological alterations of the hippocampus, which could help stratify TLE patients into those at high versus low risk of presurgical or postsurgical memory deficits. This knowledge could improve planning and prognosis of selective epilepsy surgery and neuropsychological counseling in TLE. ANN NEUROL 2020 ANN NEUROL 2020;88:170–182

Microgliosis is associated with visual memory decline in patients with temporal lobe epilepsy and hippocampal sclerosis: A clinicopathologic study

Hippocampal sclerosis (HS) is characterized by neuronal loss and gliosis. The intensity and distribution of these histopathological findings over the Cornu Ammonis (CA) subfields are important for the classification of HS and prognostication of patients with temporal lobe epilepsy (TLE). Several studies have associated the neuronal density reduction in the hippocampus with cognitive decline in patients with TLE. The current study aimed at investigating whether the expression of glial proteins in sclerotic hippocampi is associated with presurgical memory performance of patients with TLE. Before amygdalohippocampectomy, patients were submitted to memory tests. Immunohistochemical and morphometric analyses with glial fibrillary acidic protein (GFAP) for astrogliosis and human leucocyte antigen DR (HLA-DR) for microgliosis were performed in paraffin-embedded HS and control hippocampi. Sclerotic hippocampi exhibited increased gliosis in comparison with controls. In patients with TLE, the area and intensity of staining for HLA-DR were associated with worse performance in the memory tests. Glial fibrillary acidic protein was neither associated nor correlated with memory test performance. Our data suggest association between microgliosis, but not astrogliosis, with visual memory decline in patients with TLE.

The relationship between sleep duration, cognition and dementia: a Mendelian randomization study.

BackgroundShort and long sleep duration have been linked with poorer cognitive outcomes, but it remains unclear whether these associations are causal.MethodsWe conducted the first Mendelian randomization (MR) study with 77 single-nucleotide polymorphisms (SNPs) for sleep duration using individual-participant data from the UK Biobank cohort (N = 395 803) and summary statistics from the International Genomics of Alzheimer’s Project (N cases/controls = 17 008/37 154) to investigate the potential impact of sleep duration on cognitive outcomes.ResultsLinear MR suggested that each additional hour/day of sleep was associated with 1% [95% confidence interval (CI) = 0–2%; P = 0.008] slower reaction time and 3% more errors in visual-memory test (95% CI = 0–6%; P = 0.05). There was little evidence to support associations of increased sleep duration with decline in visual memory [odds ratio (OR) per additional hour/day of sleep = 1.10 (95% CI = 0.76–1.57); P = 0.62], decline in reaction time [OR = 1.28 (95% CI = 0.49–3.35); P = 0.61], all-cause dementia [OR = 1.19 (95% CI = 0.65–2.19); P = 0.57] or Alzheimer’s disease risk [OR = 0.89 (95% CI = 0.67–1.18); P = 0.41]. Non-linear MR suggested that both short and long sleep duration were associated with poorer visual memory (P for non-linearity = 3.44e–9) and reaction time (P for non-linearity = 6.66e–16).ConclusionsLinear increase in sleep duration has a small negative effect on reaction time and visual memory, but the true association might be non-linear, with evidence of associations for both short and long sleep duration. These findings suggest that sleep duration may represent a potential causal pathway for cognition.

Amyloid β Deposition and Suspected Non-Alzheimer Pathophysiology and Cognitive Decline Patterns for 12 Years in Oldest Old Participants Without Dementia

ImportanceThe prevalence of pathologic conditions of the brain associated with Alzheimer disease increases strongly with age. Little is known about the distribution and clinical significance of preclinical biomarker staging in the oldest old, when most individuals without dementia are likely to have positive biomarkers.ObjectiveTo compare the patterns of long-term cognitive decline in multiple domains by preclinical biomarker status in the oldest old without dementia.Design, Setting, and ParticipantsA longitudinal observational study with a mean (SD) of 12.2 (2.2) years (range 7.2-15.1 years) of follow-up was conducted in an academic medical center from August 24, 2000, to January 14, 2016, including and extending observations from the Ginkgo Evaluation of Memory study. A total of 197 adults who had completed the Ginkgo Evaluation of Memory study, were free of dementia, and were able to undergo magnetic resonance imaging were eligible for a neuroimaging study in 2009. Of these patients, 175 were included in the present analyses; 140 (80%) were cognitively normal and 35 (20%) had mild cognitive impairment.Main Outcomes and MeasuresBiomarker groups included amyloid β negative (Aβ−)/neurodegeneration negative (ND−), amyloid β positive (Aβ+)/ND−, Aβ−/neurodegeneration positive (ND+), and Aβ+/ND+ based on Pittsburgh Compound B retention and hippocampal volume in 2009. Participants completed baseline neuropsychological testing from 2000 to 2002 and annual testing from 2004 to 2016. Domains included memory, executive function, language, visual-spatial reasoning, and attention and psychomotor speed. Slopes of decline were evaluated with linear mixed models adjusted for age, sex, and years of education.ResultsOf the 175 participants (71 women and 104 men), at imaging, mean (SD) age was 86.0 (2.9) years (range, 82-95 years). A total of 42 participants (24.0%) were Aβ−/ND−, 32 (18.3%) were Aβ+/ND−, 35 (20.0%) were Aβ−/ND+, and 66 (37.7%) were Aβ+/ND+. On all cognitive measures, the Aβ+/ND+ group showed the steepest decline. Compared with the Aβ−/ND− group, the amyloid deposition alone (Aβ+/ND−) group showed faster decline on tests of verbal and visual memory (–0.3513; 95% CI, –0.5269 to –0.1756), executive function (0.0158; 95% CI, 0.0013-0.0303), and language (–0.1934; 95% CI, –0.3520 to –0.0348). The Aβ−/ND+ group showed faster visual memory decline than the Aβ−/ND− reference group (–0.3007; 95% CI, –0.4736 to –0.1279).Conclusions and RelevanceIn the oldest old without dementia, presence of either or both Aβ and hippocampal atrophy is typical (>75%). Isolated hippocampal volume atrophy is associated only with greater decline in memory. However, isolated Aβ is associated with decline in memory plus language and executive functions. These findings suggest different underlying pathophysiologic processes in the Aβ+/ND− and Aβ−/ND+ groups.

Baseline Neurocognitive Performance and Clearance for Athletes to Return to Contact.

Computerized neurocognitive assessments are commonly used to manage sport-related concussion. Variations in baseline performance may influence neurocognitive performance after injury as well as the amount of time needed for an athlete to be cleared for return to sport participation. To investigate the relationship between mean baseline Immediate Post-Concussion Assessment and Cognitive Test (ImPACT) scores and postconcussion reliable decline as well as the association between postconcussion cognitive decline and days missed after injury. Cross-sectional study. University concussion databank. A total of 84 collegiate athletes who sustained a concussion between 2008 and 2015 were studied. For each ImPACT composite score (verbal memory, visual memory, visual motor speed, reaction time), athletes were grouped based on the presence or absence of reliable decline and on the presence of reliable decline in 0, 1, 2, 3, or 4 cognitive domains. Outcome measures were baseline ImPACT composite scores and days missed due to concussion. Athletes with a reliable decline in visual memory scored higher on baseline visual memory than did athletes with no decline or an improvement (t82 = -2.348, P = .021, d = 0.65). When comparing athletes who displayed a reliable decline with those who showed no change or an improvement in any composite score, days missed did not differ. The number of composite scores with a reliable decline demonstrated no main effect on days missed (P = .530). Athletes who exhibited cognitive decline in most or all of the composite scores did not miss more days after injury than athletes with a decline in fewer or none of the composite scores. Athletes should be educated regarding the lack of association between baseline neurocognitive scores and the presence or absence of a reliable decline after concussion, as well as the fact that, on average, individuals with a reliable decline across multiple domains did not miss more time after concussion.

Vitamin D and Memory Decline: Two Population-Based Prospective Studies.

Vitamin D deficiency has been linked with dementia risk, cognitive decline, and executive dysfunction. However, the association with memory remains largely unknown. To investigate whether low serum 25-hydroxyvitamin D (25(OH)D) concentrations are associated with memory decline. We used data on 1,291 participants from the US Cardiovascular Health Study (CHS) and 915 participants from the Dutch Longitudinal Aging Study Amsterdam (LASA) who were dementia-free at baseline, had valid vitamin D measurements, and follow-up memory assessments. The Benton Visual Retention Test (in the CHS) and Rey's Auditory Verbal Learning Test (in the LASA) were used to assess visual and verbal memory, respectively. In the CHS, those moderately and severely deficient in serum 25(OH)D changed -0.03 SD (95% CI: -0.06 to 0.01) and -0.10 SD (95% CI: -0.19 to -0.02) per year respectively in visual memory compared to those sufficient (p = 0.02). In the LASA, moderate and severe deficiency in serum 25(OH)D was associated with a mean change of 0.01 SD (95% CI: -0.01 to 0.02) and -0.01 SD (95% CI: -0.04 to 0.02) per year respectively in verbal memory compared to sufficiency (p = 0.34). Our findings suggest an association between severe vitamin D deficiency and visual memory decline but no association with verbal memory decline. They warrant further investigation in prospective studies assessing different memory subtypes.

Nonlinear longitudinal trajectories of cholesterol and neuropsychological function.

Prior literature has identified inconsistent longitudinal associations between total cholesterol and cognitive decline. The authors examined prospective nonlinear relations of coincident trajectories of total cholesterol and cognitive function among persons free of stroke, dementia, and other neurological disease. Up to 1,601 participants from the Baltimore Longitudinal Study of Aging (aged 19-93, 51% male, 75% White) underwent fasting cholesterol measurement and neuropsychological assessment on up to 12 occasions (M = 3.2, SD = 2.1) over up to 19 years (M = 6.4, SD = 5.3) of follow-up. Mixed-effects regression analyses were adjusted for age, sex, race, education, systolic blood pressure, body mass index, cardiovascular disease, lipid-lowering medication use, smoking, alcohol use, and depressive symptoms. Analyses revealed significant longitudinal associations between quadratic total cholesterol and performance on measures of global mental status, verbal learning, executive function, and language (all ps < .05). In general, higher total cholesterol was associated with poorer middle-aged or young-old (60-69 years) cognitive performance, but better old-old (80-89 years) cognitive performance. Linear models also revealed an association between lower total cholesterol and accelerated decline in visual memory performance. Overall, results indicate nonlinear longitudinal relations of total cholesterol to cognitive decline. Whereas higher cholesterol levels were associated with cognitive decline in the middle-aged or young-old, lower cholesterol levels were related to cognitive decline among old-old participants.

Prospective analysis of the association between estrogen receptor gene variants and the risk of cognitive decline in elderly women

A plethora of data suggests a role for estrogen in cognitive function and genetic variants in the estrogen receptors ESR1 and ESR2 have been implicated in a range of hormone-sensitive diseases. It remains unknown however, whether ESR polymorphisms are associated with the risk of decline in specific domains of cognitive function. Data came from 3799 non-demented, community-dwelling elderly women recruited in France to the 3C Study. A short cognitive test battery was administered at baseline and 2, 4 and 7 years follow-up to assess global function, verbal fluency, visual memory, psychomotor speed and executive function. Detailed socio-demographic, behavioral, physical and mental health information was also gathered and genotyping of five common ESR1 and ESR2 polymorphisms was also performed. In multivariable-adjusted Cox analysis, ESR1 rs2234693 and rs9340799 were not significantly associated with the risk of decline on any of the cognitive tasks. However, significant associations with ESR2 polymorphisms were identified. The A allele of rs1256049 was associated with an increased risk of substantial decline in visual memory (HR:1.64, 95% CI: 1.23–2.18, p=0.0007), psychomotor speed (HR:1.43, 95% CI: 1.12–1.83, p=0.004), and on the incidence of Mild Cognitive Impairment (HR:1.31, 95% CI: 1.05–1.64, p=0.02). There was also a weaker association between the A allele of rs4986938 and a decreased risk of decline in psychomotor speed. Our large multicentre prospective study provides preliminary evidence that ESR2 genetic variants may be associated with specific cognitive domains and suggests that further examination of the role of this gene in cognitive function is warranted.

Cognitive trajectories associated with β-amyloid deposition in the oldest-old without dementia

To determine whether a high prevalence (55%) of Aβ deposition in a cohort of individuals remaining dementia-free into their 9th and 10th decades is associated with cognitive decline prior to imaging. A total of 194 participants (mean age 85.5 years, range 82-95) who completed the Ginkgo Evaluation of Memory Study (GEMS) and remained dementia-free subsequently completed Pittsburgh compound B-PET imaging. We examined cross-sectional associations between Aβ status and performance on a broad neuropsychological test battery completed at GEMS entry 7-9 years prior to neuroimaging. We also longitudinally examined cognition over annual evaluations using linear mixed models. At GEMS screening (2000-2002), participants who were Aβ-positive in 2009 had lower performance on the Stroop test (p < 0.01) and Raven's Progressive Matrices (p = 0.05), with trend level difference for Block Design (p = 0.07). Longitudinal analyses showed significant slope differences for immediate and delayed recall of the Rey-Osterrieth figure, semantic fluency, and Trail-Making Test parts A and B, indicating greater performance decline prior to neuroimaging for Aβ-positive relative to Aβ-negative participants (ps < 0.05). Highly prevalent Aβ deposition in oldest-older adults is associated with cognitive decline in visual memory, semantic fluency, and psychomotor speed beginning 7-9 years prior to neuroimaging. Mean differences in nonmemory domains, primarily executive functions, between Aβ-status groups may be detectable 7-9 years before neuroimaging.

Stronger effect of amyloid load than APOE genotype on cognitive decline in healthy older adults

Although the APOE ε4 allele is associated with more rapid decline in memory in healthy older adults, the significance of elevated cerebral β-amyloid (Aβ) load for longitudinal changes in cognition is unclear. Healthy and cognitively normal older adults (n = 141; mean age 76 years) underwent PET neuroimaging for cerebral Aβ, APOE genotyping, and cognitive assessment as part of their baseline assessment in the Australian Imaging Biomarkers and Lifestyle study. Cognitive function was reassessed 18 months later. Linear mixed-model analyses adjusted for baseline cognitive function indicated that, relative to individuals with low cerebral Aβ, individuals with high cerebral Aβ showed significantly greater decline in working memory and verbal and visual episodic memory at 18 months. Compared with noncarriers, APOE ε4 carriers showed a greater decline in visual memory at the 18-month assessment. No interaction between APOE ε4 and cerebral Aβ load was observed for any measure of cognitive function. In this prospective study of healthy older adults, high cerebral Aβ load was associated with greater decline in episodic and working memory over 18 months. The APOE ε4 genotype was also associated with a decline in visual memory, although the effect was less than that observed for cerebral Aβ load.

Memory Outcomes Following Selective Versus Nonselective Temporal Lobe Removal: A Systematic Review

The surgical removal of brain tissue for the treatment of temporal lobe epilepsy can be either nonselective, as with an anterior temporal lobectomy (ATL), or selective, as with a selective amygdalohippocampectomy (SAH). Although seizure outcomes are similar with both procedures, cognitive and memory outcomes remain a matter of debate. This study aims to evaluate current evidence with regard to memory outcomes in ATL and SAH. A systematic literature review was conducted combining the search term “memory” with each of the search terms “temporal lobe epilepsy surgery,”“anterior temporal lobectomy,” and “amygdalohippocampectomy,” with articles from 1995 to November 2011 included. A total of 27 articles met the inclusion criteria. These were compared using statistically significant outcomes from validated neuropsychological tests assessing verbal and visual memory. Analysis revealed that verbal memory decline is significantly associated with left ATL, while visual memory decline is significantly associated with right ATL. Evidence for memory outcomes in SAH, however, was inconclusive, as studies failed to show a consistent pattern with regard to type of memory decline and side of surgery. Surgery of the left temporal lobe relates to verbal memory decline, while surgery of the right temporal lobe relates to visual memory decline. Despite this generality, however, further research is necessary to determine the superiority of selective versus nonselective temporal surgical methods in regard to these memory outcomes and their effects on learning.

Imaging memory in temporal lobe epilepsy: predicting the effects of temporal lobe resection

Functional magnetic resonance imaging can demonstrate the functional anatomy of cognitive processes. In patients with refractory temporal lobe epilepsy, evaluation of preoperative verbal and visual memory function is important as anterior temporal lobe resections may result in material specific memory impairment, typically verbal memory decline following left and visual memory decline after right anterior temporal lobe resection. This study aimed to investigate reorganization of memory functions in temporal lobe epilepsy and to determine whether preoperative memory functional magnetic resonance imaging may predict memory changes following anterior temporal lobe resection. We studied 72 patients with unilateral medial temporal lobe epilepsy (41 left) and 20 healthy controls. A functional magnetic resonance imaging memory encoding paradigm for pictures, words and faces was used testing verbal and visual memory in a single scanning session on a 3T magnetic resonance imaging scanner. Fifty-four patients subsequently underwent left (29) or right (25) anterior temporal lobe resection. Verbal and design learning were assessed before and 4 months after surgery. Event-related functional magnetic resonance imaging analysis revealed that in left temporal lobe epilepsy, greater left hippocampal activation for word encoding correlated with better verbal memory. In right temporal lobe epilepsy, greater right hippocampal activation for face encoding correlated with better visual memory. In left temporal lobe epilepsy, greater left than right anterior hippocampal activation on word encoding correlated with greater verbal memory decline after left anterior temporal lobe resection, while greater left than right posterior hippocampal activation correlated with better postoperative verbal memory outcome. In right temporal lobe epilepsy, greater right than left anterior hippocampal functional magnetic resonance imaging activation on face encoding predicted greater visual memory decline after right anterior temporal lobe resection, while greater right than left posterior hippocampal activation correlated with better visual memory outcome. Stepwise linear regression identified asymmetry of activation for encoding words and faces in the ipsilateral anterior medial temporal lobe as strongest predictors for postoperative verbal and visual memory decline. Activation asymmetry, language lateralization and performance on preoperative neuropsychological tests predicted clinically significant verbal memory decline in all patients who underwent left anterior temporal lobe resection, but were less able to predict visual memory decline after right anterior temporal lobe resection. Preoperative memory functional magnetic resonance imaging was the strongest predictor of verbal and visual memory decline following anterior temporal lobe resection. Preoperatively, verbal and visual memory function utilized the damaged, ipsilateral hippocampus and also the contralateral hippocampus. Memory function in the ipsilateral posterior hippocampus may contribute to better preservation of memory after surgery.