Domain-specific Cognitive Decline Research Articles

Brain age and Alzheimer's-like atrophy are domain-specific predictors of cognitive impairment in Parkinson's disease

Recently, it was shown that patients with Parkinson's disease (PD) who exhibit an “Alzheimer's disease (AD)-like” pattern of brain atrophy are at greater risk for future cognitive decline. This study aimed to investigate whether this association is domain-specific and whether atrophy associated with brain aging also relates to cognitive impairment in PD. SPARE-AD, an MRI index capturing AD-like atrophy, and atrophy-based estimates of brain age were computed from longitudinal structural imaging data of 178 PD patients and 84 healthy subjects from the LANDSCAPE cohort. All patients underwent an extensive neuropsychological test battery. Patients diagnosed with mild cognitive impairment or dementia were found to have higher SPARE-AD scores as compared to patients with normal cognition and healthy controls. All patient groups showed increased brain age. SPARE-AD predicted impairment in memory, language and executive functions, whereas advanced brain age was associated with deficits in attention and working memory. Data suggest that SPARE-AD and brain age are differentially related to domain-specific cognitive decline in PD. The underlying pathomechanisms remain to be determined.

Frailty-a risk factor of global and domain-specific cognitive decline among a nationally representative sample of community-dwelling older adult U.S. Medicare beneficiaries.

frail older adults may be more vulnerable to stressors, resulting in steeper declines in cognitive function. Whether the frailty-cognition link differs by cognitive domain remains unclear; however, it could lend insight into underlying mechanisms. we tested whether domain-specific cognitive trajectories (clock-drawing test, (CDT), immediate and delayed recall, orientation to date, time, president and vice-president naming) measured annually (2011-2016) differ by baseline frailty (physical frailty phenotype) in the National Health and Aging Trends Study (n = 7,439), a nationally representative sample of older adult U.S. Medicare beneficiaries, using mixed effects models to describe repeated measures of each cognitive outcome. To determine if the association between frailty and subsequent cognitive change differed by education, we tested for interaction using the Wald test. we observed steeper declines for frail compared to non-frail participants in each domain-specific outcome, except for immediate recall. Largest differences in slope were observed for CDT (difference = -0.12 (standard deviations) SD/year, 95%CI: -0.15, -0.08). By 2016, mean CDT scores for frail participants were 1.8 SD below the mean (95%CI: -1.99, -1.67); for non-frail participants, scores were 0.8 SD below the mean (95%CI: -0.89, -0.69). Associations differed by education for global cognitive function (Pinteraction < 0.001) and for each domain-specific outcome: CDT (Pinteraction < 0.001), orientation (Pinteraction < 0.001), immediate (Pinteraction < 0.001) and delayed (Pinteraction < 0.001) word recalls. frailty is associated with lower levels and steeper declines in cognitive function, with strongest associations for executive function. These findings suggest that aetiologies are multifactorial, though primarily vascular related; further research into its association with dementia sub-types and related pathologies is critical.

Semantic fluency and processing speed are reduced in non-cognitively impaired participants with Parkinson’s disease

ABSTRACT Introduction: Parkinson’s disease (PD) is associated with a range of cognitive deficits. Few studies have carefully examined the subtle impacts of PD on cognition among patients who do not meet formal criteria for MCI or dementia. The aim of the current study was thus to describe the impact of PD on cognition in those without cognitive impairment in a well-characterized cohort. Methods: Non-cognitively impaired participants (122 with PD, 122 age- and sex-matched healthy volunteers) underwent extensive cognitive testing. Linear regression analyses compared diagnostic group performance across cognitive measures. For cognitive tasks that were significantly different between groups, additional analyses examined group differences restricting the group inclusion to PD participants with mild motor symptoms or disease duration less than 10 years. Results: Processing speed and semantic verbal fluency were significantly lower in the PD group (B = −3.77, 95% CIs [−5.76 to −1.77], p < .001, and B = −2.02, 95% CIs [−3.12, −0.92], p < .001, respectively), even after excluding those with moderate to severe motor symptoms (B = −2.73, 95% CIs [−4.94 to −0.53], p = .015 and B = −2.11, 95% CIs [−3.32 to −0.91], p < .001, respectively) or longer disease duration (B = −3.89, 95% CIs [−6.14 to −1.63], p < .001 and B = −1.58, 95% CIs [−2.78 to −0.37], p = .010, respectively). Semantic verbal fluency remained significantly negatively associated with PD diagnosis after controlling for processing speed (B = −1.66, 95% CIs [−2.79 to −0.53], p = .004). Conclusions: Subtle decline in specific cognitive domains may be present among people diagnosed with PD but without evidence to support a formal cognitive diagnosis. These results suggest the importance of early awareness of the potential for diminishing aspects of cognition in PD even among those without mild cognitive impairment or dementia.

Cerebral Microbleeds and White Matter Hyperintensities are Associated with Cognitive Decline in an Asian Memory Clinic Study.

Cerebral Small Vessel Disease (SVD); lacunes, Cerebral Microbleeds (CMBs), and White Matter Hyperintensities (WMH) have a vital role in cognitive impairment and dementia. SVD in lobar location is related to cerebral amyloid angiopathy, whereas SVD in a deep location with hypertensive arteriopathy. It remains unclear how different locations of SVD affect long-term cognitive decline. The present study aimed to analyse the association between different locations and severity of SVD with global and domain-specific cognitive decline over the follow-up interval of 3 years. We studied 428 participants who had performed MRI scans at baseline and at least 3 neuropsychological assessments. Locations of lacunes and CMBs were categorized into strictly lobar, strictly deep and mixed-location, WMH volume into anterior and posterior. The National Institute of Neurological Disorders and Stroke-Canadian Stroke Network Harmonization Neuropsychological Battery was used to assess cognitive function. To analyse the association between baseline location and severity of SVD with cognitive decline, linear regression models with generalized estimated equations were constructed to calculate the mean difference, 95% confidence interval and two-way interaction factor between time and SVD. Increased numbers of baseline CMBs were associated with a decline in global cognition as well as a decline in executive function and memory domains. Location-specific analysis showed similar results with strictly lobar CMBs. There was no association with strictly deep and mixed-location CMBs with cognitive decline. Baseline WMH volume was associated with a decline in global cognition, executive function and memory. Similar results were obtained with anterior and posterior WMH volumes. Lacunes and their locations were not associated with cognitive decline. Strictly lobar CMBs, as well as WMH volume in anterior and posterior regions, were associated with cognitive decline. Future research focuses are warranted to evaluate interventions that may prevent cognitive decline related to SVD.

Dietary patterns and trajectories of global- and domain-specific cognitive decline in the Lothian Birth Cohort 1936.

Healthy dietary patterns may protect against age-related cognitive decline, but results of studies have been inconsistent and few have had extensive longitudinal follow-up with comprehensive cognitive testing. The aim of the present study was to determine associations of dietary patterns with trajectories of global- and domain-specific cognitive change over a 12-year period. Data from 863 community-dwelling, dementia-free participants from the Lothian Birth Cohort 1936 study of ageing completed a FFQ at baseline (aged 70 years) and underwent cognitive testing at baseline, and at the ages of 73, 76, 79 and 82 years. Composite cognitive scores were constructed for four cognitive domains (visuospatial ability, processing speed, memory and verbal ability) and global cognitive function. A Mediterranean-style pattern and a traditional pattern were derived using principal component analysis of self-reported dietary intakes. In fully adjusted latent growth curve models, higher baseline adherence to the Mediterranean-style dietary pattern (β = 0·056, P = 0·009) and lower baseline adherence to the traditional dietary pattern (β = -0·087, P < 0·001) were cross-sectionally associated with better verbal ability. A slightly steeper decline in verbal ability over 12 years was observed in those with higher Mediterranean-style diet scores at baseline (β=-0·003, P = 0·008). All other associations were non-significant. Our findings in this well-characterised Scottish cohort indicate that adherence to a healthy Mediterranean-style diet is associated cross-sectionally with better verbal (crystallised) ability, with the converse being true for the traditional diet. A healthier baseline diet did not predict a reduced risk of global- or domain-specific cognitive decline.

Degeneration of structural brain networks is associated with cognitive decline after ischaemic stroke.

Over one-third of stroke patients has long-term cognitive impairment. The likelihood of cognitive dysfunction is poorly predicted by the location or size of the infarct. The macro-scale damage caused by ischaemic stroke is relatively localized, but the effects of stroke occur across the brain. Structural covariance networks represent voxelwise correlations in cortical morphometry. Atrophy and topographical changes within such distributed brain structural networks may contribute to cognitive decline after ischaemic stroke, but this has not been thoroughly investigated. We examined longitudinal changes in structural covariance networks in stroke patients and their relationship to domain-specific cognitive decline. Seventy-three patients (mean age, 67.41 years; SD = 12.13) were scanned with high-resolution magnetic resonance imaging at sub-acute (3 months) and chronic (1 year) timepoints after ischaemic stroke. Patients underwent a number of neuropsychological tests, assessing five cognitive domains including attention, executive function, language, memory and visuospatial function at each timepoint. Individual-level structural covariance network scores were derived from the sub-acute grey-matter probabilistic maps or changes in grey-matter probability maps from sub-acute to chronic using data-driven partial least squares method seeding at major nodes in six canonical high-order cognitive brain networks (i.e. dorsal attention, executive control, salience, default mode, language-related and memory networks). We then investigated co-varying patterns between structural covariance network scores within canonical distributed brain networks and domain-specific cognitive performance after ischaemic stroke, both cross-sectionally and longitudinally, using multivariate behavioural partial least squares correlation approach. We tested our models in an independent validation data set with matched imaging and behavioural testing and using split-half validation. We found that distributed degeneration in higher-order cognitive networks was associated with attention, executive function, language, memory and visuospatial function impairment in sub-acute stroke. From the sub-acute to the chronic timepoint, longitudinal structural co-varying patterns mirrored the baseline structural covariance networks, suggesting synchronized grey-matter volume decline occurred within established networks over time. The greatest changes, in terms of extent of distributed spatial co-varying patterns, were in the default mode and dorsal attention networks, whereas the rest were more focal. Importantly, faster degradation in these major cognitive structural covariance networks was associated with greater decline in attention, memory and language domains frequently impaired after stroke. Our findings suggest that sub-acute ischaemic stroke is associated with widespread degeneration of higher-order structural brain networks and degradation of these structural brain networks may contribute to longitudinal domain-specific cognitive dysfunction.

Diabetes, Cognitive Decline, and Mild Cognitive Impairment Among Diverse Hispanics/Latinos: Study of Latinos-Investigation of Neurocognitive Aging Results (HCHS/SOL).

Hispanics/Latinos are the largest ethnic/racial group in the U.S., have the highest prevalence of diabetes, and are at increased risk for neurodegenerative disorders. Currently, little is known about the relationship between diabetes and cognitive decline and disorders among diverse Hispanics/Latinos. The purpose of this study is to clarify these relationships in diverse middle-aged and older Hispanics/Latinos. The Study of Latinos-Investigation of Neurocognitive Aging (SOL-INCA) is an ancillary study of the Hispanic Community Health Study/Study of Latinos (HCHS/SOL). HCHS/SOL is a multisite (Bronx, NY; Chicago, IL; Miami, FL; and San Diego, CA), probability-sampled (i.e., representative of targeted populations), and prospective cohort study. Between 2016 and 2018, SOL-INCA enrolled diverse Hispanics/Latinos aged ≥50 years (n = 6,377). Global cognitive decline and mild cognitive impairment (MCI) were the primary outcomes. Prevalent diabetes at visit 1, but not incident diabetes at visit 2, was associated with significantly steeper global cognitive decline (βGC = -0.16 [95% CI -0.25; -0.07]; P < 0.001), domain-specific cognitive decline, and higher odds of MCI (odds ratio 1.74 [95% CI 1.34; 2.26]; P < 0.001) compared with no diabetes in age- and sex-adjusted models. Diabetes was associated with cognitive decline and increased MCI prevalence among diverse Hispanics/Latinos, primarily among those with prevalent diabetes at visit 1. Our findings suggest that significant cognitive decline and MCI may be considered additional disease complications of diabetes among diverse middle-aged and older Hispanics/Latinos.

The role of cerebral microbleeds in the incidence of post-stroke dementia

Microbleeds are a marker of cerebrovascular disease however its role in incident post-stroke dementia (PSD) remains unclear. We investigated whether microbleeds are associated with incident PSD, domain-specific cognitive impairment and cognitive decline over a 2-year follow-up; and whether microbleeds interact with acute stroke-related infarcts to synergistically affect cognitive outcomes. In a cohort of patients with first-episode mild ischemic stroke and no pre-stroke dementia, we found patients with 3 or more mixed microbleeds (presence of both lobar and deep) were 4 times more at risk of developing PSD compared to patients with no microbleeds. Patients with strictly lobar microbleeds were 10 times more at risk of developing memory impairment while patients with possible CAA-related microbleeds were 8 times more at risk of developing memory impairment compared to patients with no microbleeds. Microbleeds did not predict cognitive decline at the 2-year follow-up. Acute stroke infarcts were not related to any cognitive outcomes. Microbleeds did not interact with stroke infracts to synergistically affect cognitive outcomes. Our findings suggest that the combined effect of possible CAA and hypertension-related microbleeds play a large and direct role in incident PSD. Management of vasculopathy and amyloid deposition may positively impact cognitive outcomes after stroke.

Longitudinal and nonlinear relations of dietary and Serum cholesterol in midlife with cognitive decline: results from EMCOA study

BackgroundPrevious studies regarding the cholesterol-cognition relationship in midlife have generated conflicting results. We thus investigated whether dietary and blood cholesterol were associated with cognitive decline.MethodsParticipants were drawn from a large cohort study entitled the Effects and Mechanism Investigation of Cholesterol and Oxysterol on Alzheimer’s disease (EMCOA) study. We included 2514 participants who completed a selection of comprehensive cognitive tests and were followed for an average of 2.3 years. Blood concentrations of total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglycerides (TG) were assessed and dietary intakes were investigated by food frequency questionnaire (FFQ) at baseline. Apolipoprotein E (APOE) was genotyped by Kompetitive Allele Specific PCR (KASP) sequencing. Non-high-density lipoprotein cholesterol (Non-HDL-C) and LDL-C/HDL-C ratio were calculated. The longitudinal effects of dietary and blood cholesterol on risk of global cognitive decline (decrease in Montreal Cognitive Assessment (MoCA) > 2 points) were examined using Cox proportional hazards models. The nonlinear associations with global and domain-specific cognitive decline was evaluated with mixed effect linear models.ResultsIn Cox proportional hazards models, neither cholesterol nor egg intake was associated with a higher risk of accelerated global cognitive decline. In contrast, the higher serum concentrations of TC, LDL-C, non-HDL-C and LDL-C/HDL-C ratio were positively associated with accelerated global cognitive decline regardless of being evaluated continuously or categorically while higher HDL-C was positively associated with accelerated global cognitive decline only when being evaluated categorically (all P < 0.05). In mixed effect linear models, quadratic and longitudinal relations of dietary cholesterol and egg intakes to global cognition, processing speed and executive function were observed. Moreover, there were inverted U-shaped relations of HDL-C, with processing speed and executive function but U-shaped relations of HDL-C and LDL-C/HDL-C ratio with verbal memory. Adverse linear associations of higher LDL-C and LDL-C/HDL-C ratio with multiple cognitive comes were also revealed. Additionally adjusting for APOE genotype did not modify cholesterol-cognition associations. Dietary and serum cholesterol had variable associations with global and domain-specific cognitive decline across educational groups.ConclusionDifferential associations between dietary/serum cholesterol and cognitive decline across different domains of function were observed in a particular population of middle-aged and elderly Chinese. Interventions to improve cognitive reserve regarding dietary instruction and lipid management should be tailored according to specific target.Trial registrationEMCOA, ChiCTR-OOC-17011882, Registered 5th, July 2017-Retrospectively registered, http://www.medresman.org/uc/project/projectedit.aspx?proj=2610

Long-term Exposure to Ambient Air Pollution, APOE-ε4 status, and Trajectories of Cognitive Decline in an Urban Cohort of Older Adults

TPS 732: Neurological effects in adults, Exhibition Hall, Ground floor, August 27, 2019, 3:00 PM - 4:30 PM Background/Aim: Age-related cognitive decline is a growing public health issue as increases in life expectancy and the aging of the baby boom generation are expected to raise the prevalence of cognitive impairment and dementia. Evidence suggests that ambient air pollution from traffic and other sources may be an important risk factor for cognitive decline. We evaluated the association between long-term exposure to ambient air pollution and cognitive decline in a cohort of urban dwelling older adults and tested whether this association is modified by APOE-ε4 status, a known genetic risk factor for cognitive decline. Methods: The Washington Heights Inwood Community Aging Project (WHICAP) is a prospective, community-based study of aging and dementia in older adults in Northern Manhattan, NYC. At baseline, participants underwent neuropsychological testing and medical examinations. Follow-up assessments occur every 18-24 months. We used mixed-effects models to evaluate the association between markers of ambient air pollution (nitrogen dioxide [NO2]), fine [PM2.5], and coarse [PM10] particulate matter) and measures of global and domain-specific cognitive decline, adjusting for sociodemographic factors and temporal trends. Inverse-probability-of-censoring weights were used to account for selective attrition. Interaction terms were included in the models to assess potential effect modification by APOE-ε4 status. Results: Among 5,330 participants, individuals exposed to higher residential concentrations of NO2 (per IQR) had lower global cognitive scores at baseline (β=-0.13, 95%CI -0.19, -0.07) and more rapid decline (β=-0.05, 95%CI -0.06, -0.04), equivalent to approximately one year of aging. Results for PM2.5 and PM10 and from individual functional cognitive domains were similar. The effect of NO2 on cognitive function and decline was stronger among APOE ε4 negative individuals compared to those who were APOE-ε4 positive. Conclusions: These results add to the growing evidence base surrounding the role of air pollution on accelerated cognitive aging and brain health, particularly in aging urban populations.

Gait Characteristics and Cognitive Decline: A Longitudinal Population-Based Study.

Gait impairments are emerging predictors of dementia. However, few studies have examined whether gait predicts decline in specific cognitive domains. This study aimed to determine whether gait speed or other gait characteristics were associated with decline in specific cognitive domains and the role of the ApoE4 genotype in modifying these associations. Participants (n = 410; mean age 72.0±7.0 years) were randomly selected from the electoral roll. At baseline, gait speed was assessed using the GAITRite walkway. Gait variability in step time, step length, step width, and double support time (DST) was calculated as the standard deviation of each measure across all steps. In a subsample (n = 177), speed was measured under fast pace. The difference between usual and fast pace was calculated. At baseline, 2.6 and 4.6 years processing speed, memory, executive and visuospatial function were measured using neuropsychological tests. Multivariable mixed models were used to examine 1) associations between gait and the different cognitive domains over time and 2) whether the presence of ApoE4 genotype modified these associations. Higher DST variability was associated with greater decline in memory (p for interaction 0.03). Slow gait speed predicted decline in processing speed (p = 0.02) and visuospatial function (p = 0.03). In ApoE4 carriers, gait speed also predicted decline in memory (p = 0.02). Other gait characteristics did not predict decline in any of the cognitive domains (p > 0.05). These findings add to the evidence that gait is an early indicator of cognitive decline, but that specific gait measures may provide diagnostic insights into specific cognitive domains.

Age-related cognitive decline in myotonic dystrophy type 1: An 11-year longitudinal follow-up study.

BackgroundMyotonic dystrophy type 1 (DM1) is an inherited multi‐systemic disease involving the central nervous system (CNS) and is consequently characterized by a range of cognitive impairments. However, whether this cognitive profile progresses over time is still a matter of debate. The aim of this study was to longitudinally assess a DM1 sample, in order to compare, for the first time, this progression with that of a control group. Clinical and socio‐demographic predictive factors potentially implicated in this possible decline are analysed.MethodSeventy‐five DM1 patients with childhood, juvenile, adult, and late‐onset, and 54 control participants were re‐assessed in an 11‐year follow‐up with a comprehensive neuropsychological battery. The analyses employed were mixed ANOVA for repeated measures to test intergroup comparisons over time and multiple linear regression for predictive variable analysis.ResultsMyotonic dystrophy type 1 patients significantly worsened in visuospatial/visuoconstructive abilities and visual memory compared with controls. Multiple linear regression revealed that progression of cognitive impairment measured by copy of the Rey–Osterrieth complex figure was predicted by muscular impairment, whilst on the block design test age predicted the change with a cut‐off at 31 years of age.DiscussionA domain‐specific progressive cognitive decline was found in DM1, with visuospatial/visuoconstructive abilities showing the greatest vulnerability to the passage of time. In addition to important clinical implications, these results suggest the need for the scientific community to delve deeper into the potential mechanisms underlying early cognitive decline in this population.

Midlife adiposity predicts cognitive decline in the prospective Multicenter AIDS Cohort Study.

Obesity is a common, modifiable cardiovascular and cerebrovascular risk factor. Among people with HIV, obesity may contribute to multisystem dysregulation including cognitive impairment. We examined body mass index (BMI) and central obesity (waist circumference [WC]) in association with domain-specific cognitive function and 10-year cognitive decline in men with HIV infection (MWH) vs HIV-uninfected (HIV-) men. A total of 316 MWH and 656 HIV- Multicenter AIDS Cohort Study participants ≥40 years at baseline, with neuropsychological testing every 2 years and concurrent BMI and WC measurements, were included. MWH were included if taking ≥2 antiretroviral agents and had HIV-1 RNA <400 copies/mL at >80% of visits. Mixed-effects models included all visits from 1996 to 2015, stratified by HIV serostatus, and adjusted for sociodemographic, behavioral, and clinical characteristics. At baseline and follow-up, 8% of MWH and 15% of HIV- men and 41% of MWH and 56% of HIV- men were ≥60 years, respectively. Cross-sectionally, higher BMI was inversely associated with motor function in MWH and HIV- men, and attention/working memory in HIV- men. WC was inversely associated with motor function in MWH and HIV- men. Longitudinal associations indicated an obese BMI was associated with a less steep decline in motor function in MWH whereas in HIV- men, obesity was associated with a greater decline in motor function, learning, and memory. WC, or central obesity, showed similar patterns of associations. Higher adiposity is associated with lower cognition cross-sectionally and greater cognitive decline, particularly in HIV- men. Overweight and obesity may be important predictors of neurologic outcomes and avenues for prevention and intervention.

The relationship between domain-specific subjective cognitive decline and Alzheimer's pathology in normal elderly adults

We evaluated the associations of subjective (self-reported everyday cognition [ECog]) and objective cognitive measures with regional amyloid-β (Aβ) and tau accumulation in 86 clinically normal elderly subjects from the Alzheimer's Disease Neuroimaging Initiative. Regression analyses were conducted to identify whether individual ECog domains (Memory, Language, Organization, Planning, Visuospatial, and Divided Attention) were equally or differentially associated with regional [18F]florbetapir and [18F]flortaucipir uptake and how these associations compared to those obtained with objective cognitive measures. A texture analysis, the weighted 2-point correlation, was used as an additional approach for estimating the whole-brain tau burden without positron emission tomography intensity normalization. Although the strongest models for ECog domains included either tau (planning and visuospatial) or Aβ (memory and organization), the strongest models for all objective measures included Aβ. In Aβ-negative participants, the strongest models for all ECog domains of executive functioning included tau. Our results indicate differential associations of individual subjective cognitive domains with Aβ and tau in clinically normal adults. Detailed characterization of ECog may render a valuable prescreening tool for pathological prediction.

Neural correlates of domain-specific cognitive decline: The ARIC-NCS Study.

To evaluate the association of cognitive declines in the domains of memory, language, and executive function with brain gray matter (GM) volume in old age. This was a prospective study of 1,846 participants in the Atherosclerosis Risk in Communities (ARIC) Study who underwent 3T brain MRI scans in 2011 to 2013. Participants were categorized by cognitive domain performance trajectory over the prior 20 years (cut point to define decline: 20th percentile). Associations between GM volume and cognitive declines were assessed at the voxel level with voxel-based morphometry and at the regional level with atlas-defined GM volumes of specific regions of interest. Participants were an average age of 76 years; 60% were female; and 28% were black. Participants in the top 20th percentile for decline in the memory domain had smaller GM volumes in the medial temporal lobe (-3.3%, 95% confidence interval [CI] -4.6% to -2.1%), amygdala (-2.7%, 95% CI -4.1% to -1.3%), entorhinal cortex (-4.1%, 95% CI -6.0% to -2.2%), and hippocampus (-3.8%, 95% CI -5.2% to -2.4%) compared to participants who were in the lowest 80th percentile for decline in all domains. In contrast, among participants who were in the top 20th percentile for decline in the language or executive function domains, GM volumes were smaller in more brain regions. Declines in memory function were associated with brain volume loss in the medial temporal and hippocampal formations. Declines in language and executive function were associated with decreases in brain volumes across more noncontiguous brain regions.

Basal Forebrain Volume, but Not Hippocampal Volume, Is a Predictor of Global Cognitive Decline in Patients With Alzheimer's Disease Treated With Cholinesterase Inhibitors.

Background: Predicting the progression of cognitive decline in Alzheimer's disease (AD) is important for treatment selection and patient counseling. Structural MRI markers such as hippocampus or basal forebrain volumes might represent useful instruments for the prediction of cognitive decline. The primary objective was to determine the predictive value of hippocampus and basal forebrain volumes for global and domain specific cognitive decline in AD dementia during cholinergic treatment.Methods: We used MRI and cognitive data from 124 patients with the clinical diagnosis of AD dementia, derived from the ADNI-1 cohort, who were on standard of care cholinesterase inhibitor treatment during a follow-up period between 0.4 and 3.1 years. We used linear mixed effects models with cognitive function as outcome to assess the main effects as well as two-way interactions between baseline volumes and time controlling for age, sex, and total intracranial volume. This model accounts for individual variation in follow-up times.Results: Basal forebrain volume, but not hippocampus volume, was a significant predictor of rates of global cognitive decline. Larger volumes were associated with smaller rates of cognitive decline. Left hippocampus volume had a modest association with rates of episodic memory decline. Baseline performance in global cognition and memory was significantly associated with hippocampus and basal forebrain volumes; in addition, basal forebrain volume was associated with baseline performance in executive function.Conclusions: Our findings indicate that in AD dementia patients, basal forebrain volume may be a useful marker to predict subsequent cognitive decline during cholinergic treatment.

Severe hypoglycaemia, mild cognitive impairment, dementia and brain volumes in older adults with type 2 diabetes: the Atherosclerosis Risk in Communities (ARIC) cohort study.

We aimed to evaluate the link between severe hypoglycaemia and domain-specific cognitive decline, smaller brain volumes and dementia in adults with type 2 diabetes, which so far has been relatively poorly characterised. We included participants with diagnosed diabetes from the community-based Atherosclerosis Risk in Communities (ARIC) study. At the participants' fifth study visit (2011-2013), we examined the cross-sectional associations of severe hypoglycaemia with cognitive status, brain volumes and prior 15year cognitive decline. We also conducted a prospective survival analysis of incident dementia from baseline, visit 4 (1996-1998), to 31 December 2013. Severe hypoglycaemia was identified, using ICD-9 codes, from hospitalisations, emergency department visits and ambulance records. Prior cognitive decline was defined as change in neuropsychological test scores from visit 4 (1996-1998) to visit 5 (2011-2013). At visit 5, a subset of participants underwent brain MRIs. Analyses were adjusted for demographics, APOE genotype, use of diabetes medication, duration of diabetes and glycaemic control. Among 2001 participants with diabetes at visit 5 (mean age 76years), a history of severe hypoglycaemia (3.1% of participants) was associated with dementia (vs normal cognitive status): OR 2.34 (95% CI 1.04, 5.27). In the subset of participants who had undergone brain MRI (n = 580), hypoglycaemia was associated with smaller total brain volume (-0.308 SD, 95% CI -0.612, -0.004). Hypoglycaemia was nominally associated with a 15year cognitive change (-0.14 SD, 95% CI -0.34, 0.06). In prospective analysis (n = 1263), hypoglycaemia was strongly associated with incident dementia (HR 2.54, 95% CI 1.78, 3.63). Our results demonstrate a strong link between severe hypoglycaemia and poor cognitive outcomes, suggesting a need for discussion of appropriate diabetes treatments for high-risk older adults.

Associations between lesions and domain-specific cognitive decline in poststroke dementia.

To investigate whether the effect of prestroke and stroke-related lesions on incident poststroke dementia (PSD) is mediated by a unique pattern of domain-specific cognitive impairment, and the relative strength of these anatomical-cognitive associations in predicting incident PSD. In this incident case-control study (n = 150), we defined incident cases as acute stroke patients who developed PSD and controls as acute stroke patients who remained free from dementia at a 6 month follow-up, matched on age, prestroke cognitive status, and number of stroke-related lesions. MRI was performed at initial clinical presentation; neuropsychological assessments and clinical diagnosis of PSD was performed 6 months poststroke. Moderated mediation analysis evaluated the interactions among PSD, anatomical lesions, cognitive domains, and individual demographic and medical characteristics. Compared to stroke-related lesions, prestroke lesions were associated with the widest range of cognitive domain impairments and had stronger clinical utility in predicting incident PSD. Specifically, global cortical atrophy (GCA) and deep white matter hyperintensities (WMH) were indirectly associated with PSD by disrupting executive functions, memory, and language. Acute infarcts were indirectly associated with PSD by disrupting executive functions and language. The strongest mediator was executive dysfunction, increasing risk of PSD in patients with deep WMH, GCA, and large infarcts by more than 9 times, with sex and educational attainment moderating the magnitude of association. Periventricular WMH were directly associated with incident PSD but not mediated by deficits in cognitive domains. We provide an anatomical-cognitive framework that can be applied to stratify patients at highest risk of PSD and to guide personalized interventions.

Vitamin D Status and Intakes and Their Association With Cognitive Trajectory in a Longitudinal Study of Urban Adults.

Serum 25-hydroxyvitamin D [25(OH)D], and dietary and supplemental vitamin D may influence cognitive outcomes. Sex-, age-, and race-specific associations of vitamin D status and intake with longitudinal change in various cognitive domains were examined in a large sample of ethnically and socioeconomically diverse US urban adults. Two prospective waves of data from the Healthy Aging in Neighborhoods of Diversity across the Life Span study were used. Adults in Baltimore, Maryland, aged 30 to 64 years at baseline (n = 1231 to 1803), were followed for a mean (± standard deviation) of 4.64 ± 0.93 years. Visit 1 occurred between 2004 and 2009; visit 2, between 2009 and 2013; there were 1.5 to 2.0 visits per participant. Cognitive performance was assessed using 11 test scores covering domains of global cognition, attention, learning/memory, executive function, visuospatial/visuoconstruction ability, psychomotor speed, and language/verbal. Serum 25(OH)D, vitamin D intake, and use of supplements containing vitamin D were the key exposures. A consistent relationship was found between vitamin D status (overall) and supplemental intake (older women and black adults), with a slower rate of decline in the domain of verbal fluency. Higher dietary intake of vitamin D was linked to slower rate of decline in verbal memory among younger women, and a slower rate of decline in visual memory/visuoconstructive abilities among white adults. All other associations were inconsistent. Vitamin D status and intakes were inversely related to domain-specific cognitive decline in US urban adults.

Hearing treatment for reducing cognitive decline: Design and methods of the Aging and Cognitive Health Evaluation in Elders randomized controlled trial

IntroductionHearing impairment is highly prevalent and independently associated with cognitive decline. The Aging and Cognitive Health Evaluation in Elders study is a multicenter randomized controlled trial to determine efficacy of hearing treatment in reducing cognitive decline in older adults. Clinicaltrials.gov Identifier: NCT03243422. MethodsEight hundred fifty participants without dementia aged 70 to 84 years with mild-to-moderate hearing impairment recruited from four United States field sites and randomized 1:1 to a best-practices hearing intervention or health education control. Primary study outcome is 3-year change in global cognitive function. Secondary outcomes include domain-specific cognitive decline, incident dementia, brain structural changes on magnetic resonance imaging, health-related quality of life, physical and social function, and physical activity. ResultsTrial enrollment began January 4, 2018 and is ongoing. DiscussionWhen completed in 2022, Aging and Cognitive Health Evaluation in Elders study should provide definitive evidence of the effect of hearing treatment versus education control on cognitive decline in community-dwelling older adults with mild-to-moderate hearing impairment.