Longitudinal Cognitive Performance Research Articles

Cognitive performance before and after the onset of subjective cognitive decline in old age

BackgroundOur objectives were (1) to test the association between the report of subjective cognitive decline (SCD) and prospective objective cognitive performance in high age individuals and (2) to study the course of longitudinal cognitive performance before and after the first report of SCD. MethodsCognitively normal elderly participants of the German Study on Ageing, Cognition, and Dementia study (N = 2330) with SCD (subjective decline in memory with and without associated concerns) and without SCD at baseline were assessed over 8 years with regard to immediate and delayed verbal recall, verbal fluency, working memory, and global cognition. Baseline performance and cognitive trajectories were compared between groups. In addition, cognitive trajectories before and after the initial report of SCD (incident SCD) were modelled in those without SCD at baseline. ResultsBaseline performance in the SCD group was lower and declined more steeply in immediate and delayed verbal recall than in the control group (no SCD at baseline). This effect was more pronounced in the SCD group with concerns. Incident SCD was preceded by decline in immediate and delayed memory and word fluency. ConclusionsSCD predicts future memory decline. Incident SCD is related to previous cognitive decline. The latter finding supports the concept of SCD indicating first subtle decline in cognitive performance that characterizes preclinical Alzheimer's disease.

Calibrating Longitudinal Cognition in Alzheimer's Disease Across Diverse Test Batteries and Datasets

Background: We sought to identify optimal approaches by calibrating longitudinal cognitive performance across studies with different neuropsychological batteries. Methods: We examined four approaches to calibrate cognitive performance in nine longitudinal studies of Alzheimer's disease (AD) (n = 10,875): (1) common test, (2) standardize and average available tests, (3) confirmatory factor analysis (CFA) with continuous indicators, and (4) CFA with categorical indicators. To compare precision, we determined the minimum sample sizes needed to detect 25% cognitive decline with 80% power. To compare criterion validity, we correlated cognitive change from each approach with 6-year changes in average cortical thickness and hippocampal volume using available MRI data from the AD Neuroimaging Initiative. Results: CFA with categorical indicators required the smallest sample size to detect 25% cognitive decline with 80% power (n = 232) compared to common test (n = 277), standardize-and-average (n = 291), and CFA with continuous indicators (n = 315) approaches. Associations with changes in biomarkers changes were the strongest for CFA with categorical indicators. Conclusions: CFA with categorical indicators demonstrated greater power to detect change and superior criterion validity compared to other approaches. It has wide applicability to directly compare cognitive performance across studies, making it a good way to obtain operational phenotypes for genetic analyses of cognitive decline among people with AD. i 2014 S. Karger AG, Basel

Synergistic effect of β-amyloid and neurodegeneration on cognitive decline in clinically normal individuals.

Assessing the ability of Alzheimer disease neuroimaging markers to predict short-term cognitive decline among clinically normal (CN) individuals is critical for upcoming secondary prevention trials using cognitive outcomes. To determine whether neuroimaging markers of β-amyloid (Aβ) and neurodegeneration (ND) are independently or synergistically associated with longitudinal cognitive decline in CN individuals. Academic medical center longitudinal natural history study among 166 CN individuals (median age, 74 years; 92 women). The Aβ status was determined with Pittsburgh Compound B-positron emission tomography, while ND was assessed using 2 a priori measures, hippocampus volume (magnetic resonance imaging) and glucose metabolism (positron emission tomography with fludeoxyglucose F 18), extracted from Alzheimer disease-vulnerable regions. Based on imaging markers, CN individuals were categorized into the following preclinical Alzheimer disease stages: stage 0 (Aβ-/ND-), stage 1 (Aβ(+)/ND-), stage 2 (Aβ(+)/ND(+)), and suspected non-Alzheimer disease pathology (Aβ-/ND(+)). Cognition was assessed with a composite of neuropsychological tests administered annually. The Aβ(+) CN individuals were more likely to be classified as ND+: 59.6% of Aβ(+) CN individuals were ND(+), whereas 31.9% of Aβ- CN individuals were ND(+) (odds ratio, 3.14; 95% CI, 1.44-7.02; P = .004). In assessing longitudinal cognitive performance, practice effects were evident in CN individuals negative for both Aβ and ND, whereas diminished practice effects were observed in CN individuals positive for either Aβ or ND. Decline over time was observed only in CN individuals positive for both Aβ and ND, and decline in this group was significantly greater than that in all other groups (P < .001 for all). A significant interaction term between Aβ and ND confirmed that this decline was greater than the additive contributions of Aβ and ND (P = .04). The co-occurrence of Aβ and ND accelerates cognitive decline in CN individuals. Therefore, both factors are important to consider in upcoming secondary prevention trials targeting CN individuals at high risk for progression to the symptomatic stages of Alzheimer disease.

Caffeine and Alcohol Intakes and Overall Nutrient Adequacy Are Associated with Longitudinal Cognitive Performance among U.S. Adults

Among modifiable lifestyle factors, diet may affect cognitive health. Cross-sectional and longitudinal associations may exist between dietary exposures [e.g., caffeine (mg/d), alcohol (g/d), and nutrient adequacy] and cognitive performance and change over time. This was a prospective cohort study, the Baltimore Longitudinal Study of Aging (n = 628–1305 persons depending on the cognitive outcome; ∼2 visits/person). Outcomes included 10 cognitive scores, spanning various domains of cognition. Caffeine and alcohol intakes and a nutrient adequacy score (NAS) were estimated from 7-d food diaries. Among key findings, caffeine intake was associated with better baseline global cognition among participants with a baseline age (Agebase) of ≥70 y. A higher NAS was associated with better baseline global cognition performance (overall, women, Agebase <70 y), better baseline verbal memory (immediate and delayed recall, Agebase ≥70 y), and slower rate of decline or faster improvement in the attention domain (women). For an Agebase of <70 y, alcohol consumption was associated with slower improvement on letter fluency and global cognition over time. Conversely, for an Agebase of ≥70 y and among women, alcohol intake was related to better baseline attention and working memory. In sum, patterns of diet and cognition associations indicate stratum-specific associations by sex and baseline age. The general observed trend was that of putative beneficial effects of caffeine intake and nutrient adequacy on domains of global cognition, verbal memory, and attention, and mixed effects of alcohol on domains of letter fluency, attention, and working memory. Further longitudinal studies conducted on larger samples of adults are needed to determine whether dietary factors individually or in combination are modifiers of cognitive trajectories among adults.

Cross-sectional and longitudinal relationships between cerebrospinal fluid biomarkers and cognitive function in people without cognitive impairment from across the adult life span.

Age-related cognitive decline among older individuals with normal cognition is a complex trait that potentially derives from processes of aging, inherited vulnerabilities, environmental factors, and common latent diseases that can progress to cause dementia, such as Alzheimer disease and vascular brain injury. To use cerebrospinal fluid (CSF) biomarkers to gain insight into this complex trait. Secondary analyses of an academic multicenter cross-sectional (n = 315) and longitudinal (n = 158) study of 5 neuropsychological tests (Immediate Recall, Delayed Recall, Trail Making Test Parts A and B, and Category Fluency) in cognitively normal individuals aged 21 to 100 years. To investigate the association of these cognitive function test results with age, sex, educational level, inheritance of the ε4 allele of the apolipoprotein E gene, and CSF concentrations of β-amyloid 42 (Aβ42) and tau (biomarkers of Alzheimer disease) as well as F2-isoprostanes (measures of free radical injury). Age and educational level were broadly predictive of cross-sectional cognitive performance; of the genetic and CSF measures, only greater CSF F2-isoprostane concentration was significantly associated with poorer executive function (adjusted R2 ≤0.31). Longitudinal measures of cognitive abilities, except Category Fluency, also were associated broadly with age; of the genetic and CSF measures, only lower baseline CSF Aβ42 concentration was associated with longitudinal measures of immediate and delayed recall (marginal R2 ≤0.31). Our results suggest that age and educational level accounted for a substantial minority of variance in cross-sectional or longitudinal cognitive test performance in this large group of cognitively normal adults. Latent Alzheimer disease and other diseases that produce free radical injury, such as vascular brain injury, accounted for a small amount of variation in cognitive test performance across the adult human life span. Additional genetic and environmental factors likely contribute substantially to age-related cognitive decline.

Exploration of 100 commonly used drugs and supplements on cognition in older adults

BackgroundThere are conflicting reports and a lack of evidence-based data regarding effects of medications on cognition in cognitively normal older adults. We explored whether use of 100 common medications taken by older adults is associated with longitudinal cognitive performance. MethodsA longitudinal observational cohort was used with analysis of data collected from September 2005 through May 2011 and maintained in the National Alzheimer's Coordinating Center (NACC) Uniform Data Set. Participants were aged 50 years or older and cognitively normal (N = 4414). Composite scores were constructed from 10 psychometric tests. Scores for each participant reflecting change in the psychometric composite score from the baseline clinical assessment to the next assessment were calculated. General linear models were used to test whether the mean composite change score differed for participants who reported starting, stopping, continuing, or not taking each of the 100 most frequently used medications in the NACC sample. ResultsThe average time between assessments was 1.2 years (SD = 0.42). Nine medications showed a difference (P < .05) across the four participant groups in mean psychometric change scores from the first to the second assessment. Medications associated with improved psychometric performance were naproxen, calcium-vitamin D, ferrous sulfate, potassium chloride, flax, and sertraline. Medications associated with declining psychometric performance were bupropion, oxybutynin, and furosemide. ConclusionsReported use of common medications is associated with cognitive performance in older adults, but studies are needed to investigate the mechanisms underlying these effects.

Caffeine, alcohol and overall nutrient adequacy are associated with longitudinal cognitive performance among US adults

The relationships of caffeine, alcohol and nutrient adequacy with cognitive performance were examined using data from a prospective cohort study, the Baltimore Longitudinal Study of Aging (n=628–1,305;~2 visits/person). Outcomes included ten cognitive test scores, spanning various domains. Caffeine and alcohol intakes and a nutrient adequacy score(NAS) were estimated from 7‐d food diaries. Multiple linear mixed models (Time=years since baseline assessment), indicated that caffeine was associated with better baseline global cognition, overall and for subjects with baseline age(Agebase)≥70y. Caffeine was also related to better baseline performance on visual memory overall, but with a faster decline on that domain over time. Higher NAS was linked to slower decline on verbal memory, immediate recall(overall,men, Agebase&lt;70y) and attention(women, Agebase&lt;70y), better baseline performance on immediate and delayed recall(Agebase≥70y), but with faster decline on global cognition and visual memory(Agebase&lt;70y). For Agebase&lt;70y, alcohol was linked to faster decline on letter fluency and global cognition. Conversely, for Agebase≥70y, alcohol was related to better baseline attention and working memory. Models with Time=Age centered at 50y were consistent. In sum, mixed patterns of association indicate modification by baseline age and sex, requiring more longitudinal studies.

Alzheimer disease pathology and longitudinal cognitive performance in the oldest-old with no dementia

It has been hypothesized that individuals without dementia with Alzheimer disease (AD) neuropathology may be in the preclinical stages of dementia and could be experiencing subtle cognitive decline. The purpose of this study was to compare longitudinal cognitive performance in oldest-old individuals without dementia with and without AD neuropathology. The study included 58 individuals without dementia from The 90+ Autopsy Study, a population-based study of aging and dementia in individuals aged 90 and older. Participants had neurologic and neuropsychological testing every 6 months with an average of 3 years of follow-up. We compared the trajectory of cognitive performance on the Modified Mini-Mental State Examination (3MS) and the California Verbal Learning Test II (CVLT) by level of AD neuropathology. Based on Consortium to Establish a Registry for Alzheimer's Disease plaque staging, individuals were categorized as having low (none or sparse) or high (moderate or frequent) plaques. Based on Braak and Braak staging, participants were classified as having low (stages I-III) or high (IV-VI) tangles. No significant differences were found in 3MS or CVLT cognitive performance over time based on plaque or tangle staging. Both high and low pathology groups showed modest improvements on the 3MS and CVLT consistent with learning effects. AD neuropathology at autopsy is not associated with the trajectory of cognitive performance in the 3 years before death in oldest-old without dementia. Despite the presence of AD neuropathology at death, oldest-old without dementia display learning effects on cognitive tests. Further research is necessary to understand factors other than AD neuropathology that may affect cognition in the oldest-old.

P4‐095: Association between variants in newly discovered Alzheimer's susceptibility genes and longitudinal cognitive performance in late middle‐aged adults: The WRAP cohort

known “AD genes’” regions, AD subjects have greater rate and total length of duplications than controls. We did not find evidence for common CNV association to AD using logistic regression with numerous covariates. In chr15q11 20.2M-22.6Mwe found large (>1⁄4500 kbp) duplications are overrepresented by AD cases (47 cases, 4 controls, OR1⁄43.4). This 15q11 region is upstream of the region where deletions are associated with either PraderWilli or Angelman syndromes. The presence of abundant segmental duplications in this region makes it a hot spot for Non Allelic Homologous Recombinations (NAHRs). We were able to identify potential pairs of segmental duplications that might have facilitated some of the recurrent duplications. Conclusions: Duplications in the chr15q11 region are associated with increased risk of late onset AD in the Caucasian population.

Brain atrophy accelerates cognitive decline in cerebral small vessel disease

To examine the independent contributions and combined interactions of medial temporal lobe atrophy (MTA), cortical and subcortical atrophy, and white matter lesion (WML) volume in longitudinal cognitive performance. A total of 477 subjects with age-related WML were evaluated with brain MRI and annual neuropsychological examinations in 3-year follow-up. Baseline MRI determinants of cognitive decline were analyzed with linear mixed models controlling for multiple confounders. MTA and subcortical atrophy predicted significantly steeper rate of decline in global cognitive measures as well as compound scores for psychomotor speed, executive functions, and memory after adjusting for age, gender, education, lacunes/infarcts, and WML volume. Cortical atrophy independently predicted decline in psychomotor speed. WML volume remained significantly associated with cognitive decline even after controlling for the atrophy scores. Moreover, significant synergistic interactions were found between WML and atrophy measures in overall cognitive performance across time and the rate of cognitive decline. Synergistic effects were also observed between baseline lacunar infarcts and all atrophy measures on change in psychomotor speed. The main results remained robust after exclusion of subjects with clinical stroke or incident dementia, and after additional adjustments for progression of WML and lacunes. Brain atrophy and WML are independently related to longitudinal cognitive decline in small vessel disease. MTA, subcortical, and cortical atrophy seem to potentiate the effect of WML and lacunes on cognitive decline.

130 A pilot study of a timed short addition test as a tool for the longitudinal study of cognitive dysfunction in multiple sclerosis

Cognition is a routinely measured in Multiple Sclerosis (MS) clinical trials using the Paced Auditory Serial Addition Task (PASAT) which tests arithmetic processing via a 60 element, time-paced list of...

Abstract 3165: Influence Of Hypertension On Cognition Is Mediated By Brain Injury

Background Substantial evidence indicates that hypertension is a major risk factor for cognitive decline and incident dementia. Unfortunately, community based, longitudinal studies examining this association are limited. In addition, while it is assumed that vascular brain injury likely mediates this association, these studies are similarly limited. Methods The Sacramento Area Latino Study of Aging is a community based longitudinal study of life-style factors and cognitive performance among individuals 65 years and older. Comprehensive assessment including blood pressure measures and yearly cognitive testing was performed. In addition, a subgroup of 207 subjects received brain MRI with quantitative analysis of gray matter, hippocampus and white matter hyperintensity (WMH) volumes. We analyzed the relationship between baseline measures of blood pressure (systolic (SBP), diastolic (DBP) and pulse pressure (PP)), MRI measures and longitudinal cognitive performance over an average of six visits as measured by the 3MMSE using random mixed models regression analysis. Results On average, subject performance improved slightly during the first two visits after baseline measurement, but then began to deteriorate in a fashion best estimated by a quadratic term (trial*trial). 3MMSE performance was significantly and inversely associated with increased baseline SBP and PP, as well as linear (BP*trial) and quadratic (BP*trial*trial) declines over time (p&lt;0.03 for all comparisons). Similarly, baseline 3MMSE performance was associated with gray matter and hippocampal volumes (p &lt; 0.01 for all comparisons). Hippocampal and WMH volumes were also associated with change in 3MMSE performance over time (p &lt;0.002 for all comparisons). In a multivariate model that included blood pressure and MRI measures, the MRI associations remained significant predictors of 3MMSE performance at baseline and over time, whereas blood pressure measures were no longer significant. Conclusion The impact of elevated blood pressure on cognition is mediated through measures of brain injury. This has implications for clinical trials of blood pressure modification designed to improve cognitive health in our aging society.

Vitamin D receptor and megalin gene polymorphisms and their associations with longitudinal cognitive change in US adults

Vitamin D receptor (VDR) and the megalin gene polymorphism's link with longitudinal cognitive change remains unclear. The associations of single nucleotide polymorphisms (SNPs) for VDR [rs11568820 (CdX-2:T/C), rs1544410 (BsmI:G/A), rs7975232 (ApaI:A/C), rs731236 (TaqI:G/A)], and Megalin (rs3755166:G/A; rs2075252:C/T; rs4668123:C/T) genes with longitudinal cognitive performance changes were examined. Data from 702 non-Hispanic white participants in the Baltimore Longitudinal Study of Aging were used. Longitudinal annual rates of cognitive change (LARCCs) between age 50 y and the individual mean follow-up age were predicted with linear mixed models by using all cognitive score time points (prediction I) or time points before dementia onset (prediction II). Latent class, haplotype, and ordinary least squares (OLS) regression analyses were conducted. Among key findings, in OLS models with SNP latent classes as predictors for LARCCs, Megalin(2) [rs3755166(-)/rs2075252(TT)/rs4668123(T-)] compared with Megalin(1) [rs3755166(-)/rs2075252(CC)/rs4668123(-)] was associated with greater decline among men for verbal memory (prediction II). Significant sex differences were also found for SNP haplotype (SNPHAP). In women, VDR(1) [BsmI(G-)/ApaI(C-)/TaqI(A-); baT] was linked to a greater decline in category fluency (prediction I: β = -0.031, P = 0.012). The Megalin(1) SNPHAP (GCC) was related to greater decline among women for verbal memory, immediate recall [California Verbal Learning Test (CVLT), List A; prediction II: β = -0.043, P = 0.006) but to slower decline among men for delayed recall (CVLT-DR: β > 0, P < 0.0125; both predictions). In women, the Megalin(2) SNPHAP (ACC) was associated with slower decline in category fluency (prediction II: β = +0.026, P = 0.005). Another finding was that Megalin SNP rs3755166:G/A was associated with greater decline in global cognition in both sexes combined and in verbal memory in men. Sex-specific VDR and Megalin gene variations can modify age-related cognitive decline among US adults.

Reduced regional gray matter in cognitively normal young adults at genetic risk for early-onset Alzheimer's disease

Background: The neural mechanisms by which genetic variation increases risk for a disease have long been elusive, as there is a pathway between genes, cognitive performance, and clinical disease manifestations. We conducted a candidate gene study exploring genetic variation in brain volumes and cognitive performance measures that have been used to define heritable intermediate phenotypes related to the risk for dementia. These possible genetic bases of brain magnetic resonance imaging (MRI) measures and performance on cognitive tests were investigated in a large sample of older, community-dwelling individuals. Methods: We employed data from 997 non-demented participants (M 1⁄4 528, F 1⁄4 469; age range 1⁄4 50-92) who were prospectively followed through the Baltimore Longitudinal Study of Aging (BLSA). 119 of them also underwent annual MRI assessments. We performed both cross sectional and longitudinal analyses with APOE, a known AD risk gene, and four other putative genes for cognitive impairment and dementia (COMT, BDNF, SORL1, and KIBRA) as predictors. We used linear mixed effects models, adjusting for sex and education, to relate single nucleotide polymorphisms (SNPs; Illumina 550K Human Gene Chip) to 16 global and regional brain volumes and to performance on 12 standard cognitive tests spanning five cognitive domains (memory, word knowledge, attention, executive function, and visuo-spatial abilities). Results: Our findings provide evidence for gene associations with both cross-sectional and longitudinal cognitive performance, with the most persistent and selective associations observed between the decline in executive function (Trails B) and SORL1 and KIBRA respectively (p‘ s< 0.05). Polymorphisms in BDNF and COMT showed evidence for cross-sectional associations with white matter volume, while SORL1 polymorphisms were related to both cross-sectional and longitudinal differences specific to whole brain and white matter volume (p’ s< 0.05). Conclusions: Our results suggest that putative genes for cognitive impairment and dementia also have detectable effects on cognition and brain volume in non-demented older adults. This approach may not only aid in the discovery of novel pathways involved in structural and functional brain aging, but may also lead to better understanding of individual differences in brain structure and function.

Cognitive Decline and Brain Volume Loss as Signatures of Cerebral Amyloid-β Peptide Deposition Identified With Pittsburgh Compound B

To examine the relation of amyloid-beta peptide (Abeta) levels in the cerebral cortex with structural brain integrity and cognitive performance in cognitively healthy older people. Longitudinal study from May 22, 1985, through October 15, 2008. Washington University Alzheimer Disease Research Center. A total of 135 individuals aged 65 to 88 years with a Clinical Dementia Rating of 0. The relations between mean cortical carbon 11 ((11)C)-labeled Pittsburgh compound B (PiB) binding potential values, proportional to the density of fibrillar Abeta binding sites in the brain, concurrent regional brain volumes as assessed by magnetic resonance imaging, and both concurrent and longitudinal cognitive performance in multiple domains. Elevated cerebral Abeta levels, in some cases comparable to those seen in individuals with Alzheimer disease, were observed in 29 participants, who also had smaller regional volumes in the hippocampus, temporal neocortex, anterior cingulate, and posterior cingulate. Concurrent cognitive performance was unrelated to Abeta levels but was related to regional brain volumes with the exception of the caudate. Longitudinal cognitive decline in episodic and working memory and visuospatial ability was associated with elevated Abeta levels and decreased hippocampal volume. The in vivo measure of cerebral amyloidosis known as [(11)C]PiB is associated with cross-sectional regionally specific brain atrophy and longitudinal cognitive decline in multiple cognitive domains that occur before the clinical diagnosis of Alzheimer disease. These findings contribute to the understanding of the cognitive and structural consequences of Abeta levels in cognitively healthy older adults.

Longitudinal Study of the Transition From Healthy Aging to Alzheimer Disease

Detection of the earliest cognitive changes signifying Alzheimer disease is difficult. To model the cognitive decline in preclinical Alzheimer disease. Longitudinal archival study comparing individuals who became demented during follow-up and people who remained nondemented on each of 4 cognitive factors: global, verbal memory, visuospatial, and working memory. Alzheimer Disease Research Center, Washington University School of Medicine, St Louis, Missouri. One hundred thirty-four individuals who became demented during follow-up and 310 who remained nondemented. Inflection point in longitudinal cognitive performance. The best-fitting model for each of the 4 factors in the stable group was linear, with a very slight downward trend on all but the Visuospatial factor. In contrast, a piecewise model with accelerated slope after a sharp inflection point provided the best fit for the group that progressed. The optimal inflection point for all 4 factors was prior to diagnosis of dementia: Global, 2 years; Verbal and Working Memory, 1 year; and Visuospatial, 3 years. These results were also obtained when data were limited to the subset (n = 44) with autopsy-confirmed Alzheimer disease. There is a sharp inflection point followed by accelerating decline in multiple domains of cognition, not just memory, in the preclinical period in Alzheimer disease when there is insufficient cognitive decline to warrant clinical diagnosis using conventional criteria. Early change was seen in tests of visuospatial ability, most of which were speeded. Research into early detection of cognitive disorders using only episodic memory tasks may not be sensitive to all of the early manifestations of disease.

Longitudinal cognitive performance in older adults with cardiovascular disease: evidence for improvement in heart failure.

Cardiovascular disease (CVD) and particularly heart failure (HF) have been associated with cognitive impairment in cross-sectional studies, but it is unclear how cognitive impairment progresses over time in older adults with these conditions. The aim of this study was to prospectively examine cognitive function in patients with HF versus other forms of CVD. Seventy-five older adults (aged 53-84 years) with CVD underwent Doppler echocardiogram to evaluate cardiac status and 2 administrations of the Dementia Rating Scale (DRS), a test of global cognitive functioning, 12 months apart. Although DRS performance did not statistically differ between groups at either administration, a significant between-group difference in the rate of cognitive change emerged (lambda = 0.87; F = 10.50; P = .002; omega 2 = 0.11). Follow-up analyses revealed that patients with HF improved significantly on global DRS performance, whereas patients with other forms of CVD remained stable. More specifically, patients with HF showed improvement on subscales of attention, initiation/perseveration, and conceptualization. Exploratory analyses indicated that higher diastolic blood pressure at baseline was associated with improved DRS performance in patients with HF (r = 0.38; P = .02). Patients with HF exhibited modest cognitive improvements during 12 months, particularly in attention and executive functioning. Higher diastolic blood pressure at baseline was associated with improvement. These results suggest that cognitive impairment in patients with HF may be modifiable and that improved blood pressure control may be an important contributor to improved function. Further prospective studies are needed to replicate results and determine underlying mechanisms.

Longitudinal Cognitive Decline in Subcortical Ischemic Vascular Disease – The LADIS Study

Background: Cross-sectional studies have indicated that subcortical ischemic vascular disease (SIVD), as defined according to imaging criteria, is associated with a specific clinical and cognitive profile. Much less is known about the long-term cognitive consequences of SIVD. The aim of the study was to investigate the longitudinal cognitive performance and incident dementia in subjects with and without SIVD in a sample of older adults with white matter lesions. Methods: In the Leukoaraiosis and Disability (LADIS) study, 639 participants were examined with annual clinical and neuropsychological evaluations for 3 years. The subjects meeting the MRI criteria of SIVD at baseline were compared to the other subjects of the sample with linear mixed models. Results: The overall level of cognitive performance over the follow-up period was inferior in multiple cognitive domains in SIVD subjects as compared to the reference group. The subjects with SIVD presented significantly steeper decline of performance in the Stroop test (parts I and II), Trail Making A test, Verbal fluency test, and Mini-Mental State Examination. They also had a threefold risk of developing dementia during follow-up independently of age, sex, education and medial temporal lobe atrophy. Conclusions: SIVD, as a manifestation of cerebral small vessel disease, is related to progressive cognitive impairment and a considerable risk of developing dementia. SIVD seems to specifically contribute to the deterioration of psychomotor speed, executive control, and global cognitive function.

Can Cognitive Exercise Prevent the Onset of Dementia? Systematic Review of Randomized Clinical Trials with Longitudinal Follow-up

Epidemiological and preclinical studies suggest that mental activity levels may alter dementia risk. Clinical trials are now beginning to address the key issues of persistence of effect over extended follow-up and transfer of effect to nontrained domains. The aim of this report was to therefore systematically review results from clinical trials, which have examined the effect of cognitive exercise on longitudinal cognitive performance in healthy elderly individuals. MEDLINE, PubMed, and key references were used to generate an initial list of relevant studies (N = 54). These were reviewed to identify randomized controlled trials, which tested the effect of a discrete cognitive exercise training regime on longitudinal (>3 months) posttraining neuropsychological performance in healthy older adults. Seven RCTs met entry criteria. Prechange and postchange scores were integrated using a random effects weighted mean difference (WMD) meta-analytic approach (Review Manager Version 4.2). A strong effect size was observed for cognitive exercise interventions compared with wait-and-see control conditions (WMD = 1.07, CI: 0.32-1.83, z = 2.78, N = 7, p = 0.006, N = 3,194). RCTs with follow-up greater than 2 years did not appear to produce lower effect size estimates than those with less extended follow-up. Quality of reporting of trials was in general low. Cognitive exercise training in healthy older individuals produces strong and persistent protective effects on longitudinal neuropsychological performance. Transfer of these effects to dementia-relevant domains such as general cognition and daily functioning has also been reported in some studies. Importantly, cognitive exercise has yet to be shown to prevent incident dementia in an appropriately designed trial and this is now an international priority.

Hormone Replacement Therapy and Longitudinal Cognitive Performance in Postmenopausal Women

The authors examined the impact of hormone replacement therapy (HRT) on longitudinal cognitive performance (controlling for mood state) in 69 community-dwelling, postmenopausal women. The authors conducted a 5-year follow-up of cognitive performance in 37 postmenopausal HRT users and 32 non-users. The groups did not differ with respect to age, years of education, or inter-test interval. No main effect of HRT was observed on any of the cognitive measures, and depressive symptomatology did not affect the relationship between HRT and cognition. Overall, our findings do not suggest that HRT affects longitudinal cognitive performance in postmenopausal, community-dwelling older women.