Criteria For Mild Cognitive Impairment Research Articles

The Longitudinal Early-onset Alzheimer's Disease Study (LEADS): Framework and methodology.

Patients with early‐onset Alzheimer's disease (EOAD) are commonly excluded from large‐scale observational and therapeutic studies due to their young age, atypical presentation, or absence of pathogenic mutations. The goals of the Longitudinal EOAD Study (LEADS) are to (1) define the clinical, imaging, and fluid biomarker characteristics of EOAD; (2) develop sensitive cognitive and biomarker measures for future clinical and research use; and (3) establish a trial‐ready network. LEADS will follow 400 amyloid beta (Aβ)‐positive EOAD, 200 Aβ‐negative EOnonAD that meet National Institute on Aging–Alzheimer's Association (NIA‐AA) criteria for mild cognitive impairment (MCI) or AD dementia, and 100 age‐matched controls. Participants will undergo clinical and cognitive assessments, magnetic resonance imaging (MRI), [18F]Florbetaben and [18F]Flortaucipir positron emission tomography (PET), lumbar puncture, and blood draw for DNA, RNA, plasma, serum and peripheral blood mononuclear cells, and post‐mortem assessment. To develop more effective AD treatments, scientists need to understand the genetic, biological, and clinical processes involved in EOAD. LEADS will develop a public resource that will enable future planning and implementation of EOAD clinical trials.

Using historical data to facilitate clinical prevention trials in Alzheimer disease? An analysis of longitudinal MCI (mild cognitive impairment) data sets

BackgroundThe Placebo Group Simulation Approach (PGSA) aims at partially replacing randomized placebo-controlled trials (RPCTs), making use of data from historical control groups in order to decrease the needed number of study participants exposed to lengthy placebo treatment. PGSA algorithms to create virtual control groups were originally derived from mild cognitive impairment (MCI) data of the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database. To produce more generalizable algorithms, we aimed to compile five different MCI databases in a heuristic manner to create a “standard control algorithm” for use in future clinical trials.MethodsWe compared data from two North American cohort studies (n=395 and 4328, respectively), one company-sponsored international clinical drug trial (n=831) and two convenience patient samples, one from Germany (n=726), and one from Switzerland (n=1558).ResultsDespite differences between the five MCI samples regarding inclusion and exclusion criteria, their baseline demographic and cognitive performance data varied less than expected. However, the five samples differed markedly with regard to their subsequent cognitive performance and clinical development: (1) MCI patients from the drug trial did not deteriorate on verbal fluency over 3 years, whereas patients in the other samples did; (2) relatively few patients from the drug trial progressed from MCI to dementia (about 10% after 4 years), in contrast to the other four samples with progression rates over 30%.ConclusionConventional MCI criteria were insufficient to allow for the creation of well-defined and internationally comparable samples of MCI patients. More recently published criteria for MCI or “MCI due to AD” are unlikely to remedy this situation. The Alzheimer scientific community needs to agree on a standard set of neuropsychological tests including appropriate selection criteria to make MCI a scientifically more useful concept. Patient data from different sources would then be comparable, and the scientific merits of algorithm-based study designs such as the PGSA could be properly assessed.

799 Automated Detection of Slow Wave Coherence in Sleep EEG: A potential neurophysiological correlate of cognitive decline

Abstract Introduction A bidirectional relationship exists between sleep disruption and neuropathology in Alzheimer’s disease (AD). The sleep electroencephalogram (EEG) is a highly stereotyped, direct neurophysiological window into brain function; prior studies have identified abnormalities in EEG slow waves in early AD. EEG coherence across channels during sleep, a normally highly coherent brain state, could be an indicator of network coordination across brain regions. Accordingly, altered slow wave coherence during sleep may be an early indicator of cognitive decline. Methods EEG was collected during an attended overnight polysomnogram (PSG) from a community-based cohort of older subjects (n=44, average age = 71), approximately 25% of whom met criteria for mild cognitive impairment or early AD. Files were exported to EDF and a slow wave peak detector was implemented in MATLAB to count the number of slow wave oscillations, with automated artifact rejection, across 6 EEG leads standard for PSG (C3, C4, F3, F4, O1, and O2). Slow wave coherence was inferred when slow waves occurred in temporal synchrony across channels within 100 ms. Results Subjects with cognitive impairment showed significantly reduced total sleep time and time spent in rapid eye movement (REM) sleep compared to age-matched controls. EEG slow wave coherence was reliably quantified during wake, non-REM stages N1, N2, N3, and REM vigilance states as well as during transition periods between sleep stages. Using this algorithm, specific signatures of slow wave propagation during sleep were identified, including increased variability in slow wave activity and coherence, that appeared more prominent in subjects with impaired cognition. Conclusion EEG slow wave coherence during sleep and wake states can be calculated by applying automated algorithms to PSG data, and may be associated with cognitive impairment. Support (if any) NIH R01 AG059507

Cognitive profile and mild cognitive impairment in people with chronic lower back pain

A growing body of evidence suggests Chronic Lower Back Pain (CLBP) is associated with cognitive dysfunction. Little is known, however, about the extent of cognitive impairment in CLBP. The present study explored the cognitive profile of people with CLBP and sought to determine the extent of Mild Cognitive Impairment (MCI) according to the DSM-V and the Movement Disorders Society criteria for MCI. Thirty-one participants with CLBP and 27 age and gender matched healthy controls completed a full neuropsychological battery, consisting of two tasks for each of the five cognitive domains (Executive Function, Attention/Working Memory, Memory, Language, and Visuospatial). Participants with CLBP performed worse, compared to controls, on measures of Attention/Working Memory, Memory, Language, and Visuospatial performance. Cognitive performance in CLBP was also compared to equivalent normative data to determine cognitive impairment. Sixteen CLBP participants were impaired on at least one cognitive measure, with 5 participants meeting criteria for MCI. MCI was not associated with pain-related experience, or psychological health. The present study supports and extends previous findings that CLBP is associated with cognitive dysfunction and some people with CLBP meet criteria for MCI. These findings support that rehabilitation in people with CLBP requires a multidisciplinary approach.

Neural signatures of predictive language processing in Parkinson's disease with and without mild cognitive impairment

Cognitive deficits are common in Parkinson's disease (PD), with some PD patients meeting criteria for mild cognitive impairment (MCI). An unaddressed question is whether linguistic prediction is preserved in PD. This ability is nowadays deemed crucial for achieving fast and efficient comprehension, and it may be negatively impacted by cognitive deterioration in PD. To fill this gap of knowledge, we used event-related potentials (ERPs) to evaluate mechanisms of linguistic prediction in a sample of PD patients (on dopamine compensation) with and without MCI. To this end, participants read sentence contexts that were predictive or not about a sentence-final word. The final word appeared after one sec, matching or mismatching the prediction. The introduction of the interval allowed to capture neural responses both before and after sentence-final words, reflecting semantic anticipation and semantic processing. PD patients with normal cognition (N = 58) showed ERP responses comparable to those of matched controls. Specifically, in predictive contexts, a slow negative potential developed prior to sentence-final words, reflecting semantic anticipation. Later, expected words elicited reduced N400 responses (compared to unexpected words), indicating facilitated semantic processing. PD patients with MCI (N = 20) showed, in addition, a prolongation of the N400 congruency effect (compared to matched PD patients without MCI), indicating that further cognitive decline impacts semantic processing. Finally, lower verbal fluency scores correlated with prolonged N400 congruency effects and with reduced pre-word differences in all PD patients (N = 78). This relevantly points to a role of deficits in temporal-dependent mechanisms in PD, besides prototypical frontal dysfunction, in altered semantic anticipation and semantic processing during sentence comprehension.

Assessing the capacity for mental manipulation in patients with statically-determined mild cognitive impairment using digital technology

Aims: Prior research employing a standard backward digit span test has been successful in operationally defining neurocognitive constructs associated with the Fuster’s model of executive attention. The current research sought to test if similar behavior could be obtained using a cross-modal mental manipulation test. Methods: Memory clinic patients were studied. Using Jak-Bondi criteria, 24 patients were classified with mild cognitive impairment (MCI), and 33 memory clinic patients did not meet criteria for MCI (i.e. non-MCI). All patients were assessed with the digital version of the WRAML-2 Symbolic Working Memory Test-Part 1, a cross-modal mental manipulation task where patients hear digits, but respond by touching digits from lowest to highest on an answer key. Only 4 and 5-span trials were analyzed. Using an iPad, all test stimuli were played; and, all responses were obtained with a touch key. Only correct trials were analyzed. Average time to complete trials and latency for each digit was recorded. Results: Groups did not differ when average time to complete 4-span trials was calculated. MCI patients displayed slower latency, or required more time to re-order the 1st and 3rd digits. Regression analyses, primarily involving initial and latter response latencies, were associated with better, but different underlying neuropsychological abilities. Almost no 5-span analyses were significant. Conclusions: This cross-modal test paradigm found no difference for total average time. MCI patients generated slower 1st and 3rd response latency, suggesting differences in time allocation to achieve correct serial order recall. Moreover, different neuropsychological abilities were associated with different time-based test components. These data extend prior findings using a standard backward digit span test. Differences in time epochs are consistent with constructs underlying the model of executive attention and help explain mental manipulation deficits in MCI. These latency measures could constitute neurocognitive biomarkers that track emergent disease.

Body Temperature Is Associated With Cognitive Performance in Older Adults With and Without Mild Cognitive Impairment: A Cross-sectional Analysis.

Wearable devices for remote and continuous health monitoring in older populations frequently include sensors for body temperature measurements (i.e., skin and core body temperatures). Healthy aging is associated with core body temperatures that are in the lower range of age-related normal values (36.3 ± 0.6°C, oral temperature), while patients with Alzheimer’s disease (AD) exhibit core body temperatures above normal values (up to 0.2°C). However, the relation of body temperature measures with neurocognitive health in older adults remains unknown. This study aimed to explore the association of body temperature with cognitive performance in older adults with and without mild cognitive impairment (MCI). Eighty community-dwelling older adults (≥65 years) participated, of which 54 participants were cognitively healthy and 26 participants met the criteria for MCI. Skin temperatures at the rib cage and the scapula were measured in the laboratory (single-point measurement) and neuropsychological tests were conducted to assess general cognitive performance, episodic memory, verbal fluency, executive function, and processing speed. In a subgroup (n = 15, nine healthy, six MCI), skin and core body temperatures were measured continuously during 12 h of habitual daily activities (long-term measurement). Spearman’s partial correlation analyses, controlled for age, revealed that lower median body temperature and higher peak-to-peak body temperature amplitude was associated with better general cognitive performance and with better performance in specific domains of cognition; [e.g., rib median skin temperature (single-point) vs. processing speed: rs = 0.33, p = 0.002; rib median skin temperature (long-term) vs. executive function: rs = 0.56, p = 0.023; and peak-to-peak core body temperature amplitude (long-term) vs. episodic memory: rs = 0.51, p = 0.032]. Additionally, cognitively healthy older adults showed lower median body temperature and higher peak-to-peak body temperature amplitude compared to older adults with MCI (e.g., rib median skin temperature, single-point: p = 0.035, r = 0.20). We conclude that both skin and core body temperature measures are potential early biomarkers of cognitive decline and preclinical symptoms of MCI/AD. It may therefore be promising to integrate body temperature measures into multi-parameter systems for the remote and continuous monitoring of neurocognitive health in older adults.

Cognitive subtypes in individuals with essential tremor seeking deep brain stimulation

Objective: Essential tremor (ET) is a common neurological disorder that has been associated with 60% increased risk of developing dementia. The goals of the present study were to: (a) learn whether individuals with advanced ET symptoms seeking deep brain stimulation (DBS) surgery would fall into distinct cognitive subgroups, and (b) learn how empirically derived subgroups map onto criteria for mild cognitive impairment (MCI). Method: Patients with ET (N = 201; mean age = 68.9 ± 8.9 years) undergoing pre-surgical evaluation for DBS completed a multi-domain neurocognitive assessment consisting of memory, executive function, visuospatial skill, language, and processing speed. Two cluster analytic approaches (K-means, hierarchical) were independently conducted to classify cognitive patterns using domain composites. Demographics, clinical characteristics, and proportion of cases meeting neuropsychologically defined criteria for MCI were examined among clusters. Results: A three-cluster solution reflected a Low Executive group (N = 64), Low Memory Multi-Domain group (N = 41), and Cognitively Normal group (N = 96). The Cognitively Normal group was older and more educated, with a higher Dementia Rating Scale-2 score. In total, 27.4% of participants met criteria for MCI. Of the MCI cases, most were in the Low Executive (41.8%) or Low Memory Multi-Domain groups (49.1%). In the latter, 65.9% of its members were classified as MCI versus 35.9% in the Low Executive group. Conclusions: Our study identified three cognitive subtypes of ET patients presenting for DBS. Future work should examine the subgroups for progression to dementia, particularly the Low Memory Multi-Domain subgroup which may be at highest risk.

The oral microbiome and inflammation in mild cognitive impairment.

Inflammation and immune mechanisms are believed to play important roles in Alzheimer's disease pathogenesis. Research supports the link between poor oral health and Alzheimer's disease. Periodontal disease and dental caries represent the two most common infections of the oral cavity. This study focused on a precursor to Alzheimer's disease, mild cognitive impairment (MCI). Using 16S rRNA sequencing, we characterized and compared the oral microbiome of 68 older adults who met the criteria for MCI or were cognitively normal, then explored relationships between the oral microbiome, diagnostic markers of MCI, and blood markers of systemic inflammation. Two taxa, Pasteurellacae and Lautropia mirabilis were identified to be differentially abundant in this cohort. Although systemic inflammatory markers did not differentiate the two groups, differences in five cerebrospinal fluid inflammatory mediators were identified and had significant associations with MCI. Because inflammatory markers may reflect CNS changes, pursuing this line of research could provide opportunities for new diagnostic tools and illuminate mechanisms for prevention and mitigation of Alzheimer's disease.

Differential effects of sex on longitudinal patterns of cognitive decline in Parkinson\u2019s disease

BackgroundCognitive impairment is an important and diverse symptom of Parkinson’s disease (PD). Sex is a purported risk variable for cognitive decline in PD, but has not been comprehensively investigated.ObjectivesThis cross-sectional and longitudinal study examined sex differences in global and domain-specific cognitive performance in a large PD cohort.MethodsCognitive function was evaluated using the Addenbrooke’s Cognitive Examination in 392 people with PD (PwP) from the Australian Parkinson’s Disease Registry. The influence of sex on domain-specific cognitive performance was investigated using covariate-corrected generalised linear models. In a repeated measures longitudinal subset of 127 PwP, linear mixed models were used to assess the impact of sex on cognition over time, while accounting for covariates.ResultsCross-sectional-corrected modelling revealed that sex was significantly predictive of cognitive performance, with males performing worse than females on global cognition, and memory and fluency domains. Longitudinally, sex was significantly predictive of cognitive decline, with males exhibiting a greater reduction in global cognition and language, whereas females showed a greater decline in attention/orientation, memory and visuospatial domains, despite starting with higher baseline scores. At follow-up, a significantly higher proportion of males than females fulfilled criteria for mild cognitive impairment or PD dementia.ConclusionsSex was revealed as a significant determinant of overall cognitive performance as well as specific cognitive domains, with a differential pattern of decline in male and female participants. Such sex-specific findings appear to explain some of the heterogeneity observed in PD, warranting further investigation of mechanisms underlying this sexual dimorphism.

Photobiomodulation Enhances Memory Processing in Older Adults with Mild Cognitive Impairment: A Functional Near-Infrared Spectroscopy Study.

Recent studies of photobiomodulation (PBM) in patients with cognitive or psychological disorders (including traumatic brain injury, stroke, and dementia) have yielded some encouraging results. In this study, we aimed to investigate the effect of a single stimulation on memory in older adults with mild cognitive impairment (MCI). After PBM, hemodynamic changes, as a measure of functional brain activity, were evaluated using functional near-infrared spectroscopy (fNIRS). Eighteen subjects who met the criteria of MCI were randomly assigned to control and experimental groups. A single real or sham PBM session was administered to the forehead of each patient in the experimental and control groups, respectively. All subjects performed a visual memory span test before and after the stimulation, and their hemodynamic responses during the tasks were measured using fNIRS. The results showed that among the MCI subjects, only those who received PBM, but not those who received the sham stimulation, demonstrated significant improvement in the visual memory performance and a reduction in the hemodynamic response during the tasks. These findings suggest that PBM may reduce the cognitive efforts needed to complete tasks that require high memory loads, and thus improve the cognitive performance of individuals with MCI.

Distinguishing Amnestic Mild Cognitive Impairment From HIV-Associated Neurocognitive Disorders

Memory impairment occurs in human immunodeficiency virus (HIV)-associated neurocognitive disorders (HAND) and amnestic mild cognitive impairment (aMCI), the precursor to Alzheimer disease (AD). Methods are needed to distinguish aMCI-associated from HAND-associated impairment in people with HIV (PWH). We developed a neuropsychological method of identifying aMCI in PWH and tested this by relating AD neuropathology (β-amyloid, phospho-Tau) to aMCI versus HAND classification. Seventy-four HIV-positive cases (aged 50-68 years) from the National NeuroAIDS Tissue Consortium had neurocognitive data within 1 year of death and data on β-amyloid and phospho-Tau pathology in frontal brain tissue. High aMCI risk was defined as impairment (<1.0 SD below normative mean) on 2 of 4 delayed recall or recognition outcomes from a verbal and nonverbal memory test (at least 1 recognition impairment required). Differences in β-amyloid and phospho-Tau by aMCI and HAND classification were examined. High aMCI risk was more common in HAND (69.0%) versus no HAND (37.5%) group. β-amyloid pathology was 4.75 times more likely in high versus low aMCI risk group. Phospho-Tau pathology did not differ between aMCI groups. Neither neuropathological feature differed by HAND status. Amnestic mild cognitive impairment criteria that include recognition impairment may help to detect AD-like cognitive/biomarker profiles among PWH.

Variability in working memory performance on mobile devices is sensitive to mild cognitive impairment: Results from the Einstein Aging Study

AbstractBackgroundMost prior research on distinguishing cognitive impairment from healthy controls focuses on measuring mean‐level of cognitive performance on one or relatively few assessments, ignoring potentially valuable information about variability. Within‐person variability in cognitive performance is emerging as a promising indicator of mild cognitive impairment (MCI) and dementia. The limited research on this topic, however, typically examines speeded responses and variability transpiring across moments during a single test administration. The current study extends prior work by using ecological momentary assessments (EMA) to examine cognitive status differences in variability across hours and days in three dimensions of working memory (WM): object‐location binding, object‐feature binding, and spatial WM.MethodIn a sample of 243 systematically recruited, community‐dwelling adults age 70+ from the Einstein Aging Study (Mean age=77.46 years, SD=5.13), we identified 68 individuals meeting Jak‐Bondi criteria for MCI and 175 cognitively normal controls (Table 1). All participants performed object‐location binding, object‐feature binding, and spatial WM tasks on a smartphone up to four times daily for 14 days, totaling up to 56 assessments per person. We employed heterogeneous variance models using log‐linear prediction of residual variance to simultaneously assess MCI differences in mean performance and within‐person variability. Models adjusted for linear trends across assessments and study days, as well as age, education, gender, and ethnicity (Table 2; Figure 1).ResultsFor mean performance, individuals with MCI exhibited worse performance than healthy controls in measures of object‐location binding (Est.=0.14, SE=0.02, p&lt;.001), object‐feature binding (Est.=‐0.27, SE=0.04, p&lt;.001), and spatial WM (Est.=0.90, SE=0.20, p&lt;.001). For variability across assessments, individuals with MCI exhibited greater within‐person variability than controls in object‐location binding (Est.=0.89, SE=0.03, p&lt;.001) and object‐feature binding (Est.=0.37, SE=0.03, p&lt;.001) performance. Variability in spatial WM performance did not vary as a function of cognitive status (Est.=0.02, SE=0.03, p=.63).ConclusionResults suggest both mean and variability in performance are sensitive to MCI and exhibit dissociative patterns by WM dimension. Variability in object‐location and object‐feature binding performance may provide specific detection of MCI. The 14‐day smartphone‐based EMA offers novel opportunity to leverage performance variability across frequent assessments for identifying early clinical manifestations of cognitive impairment.

Memory impairment is a clinical marker of tau pathology in cerebral amyloid angiopathy

AbstractBackgroundCerebral Amyloid Angiopathy (CAA) shows a high comorbidity with Alzheimer’s Disease (AD). Nonetheless, CAA is an independent neuropathological disorder, and over half of CAA cases present without AD‐related tau pathology. Differentiating CAA patients with or without concomitant tau pathology could have important implications for therapeutic approaches. We aimed to determine whether memory impairments in CAA are indicative of underlying tau pathology.MethodThis study included 29 patients fulfilling criteria for mild cognitive impairment (MCI) and probable CAA. Subjects underwent a neuropsychological evaluation, a MRI, and PET scans for in‐vivo estimation of amyloid ([11C]– PiB) and tau ([18F]‐AV‐1451) burden. Structural markers of small vessel disease, total brain volume and hippocampal volume were quantified on MRI images. [11C]‐PiB specific binding was expressed as distribution volume ratios (DVR) and [18F]‐AV‐1451 specific binding as standardized uptake value ratio (SUVR), using the cerebellar cortex as the reference region. CAA subjects were classified as “amnestic” or “non‐amnestic” based on neuropsychological performance. Groups were contrasted on demographic features and quantified MRI markers. Between‐group voxel‐wise comparisons of SUVR [18F]‐AV‐1451 and DVR [11C]‐PiB maps were performed. Mean [18F]‐AV‐1451 SUVR in areas of group differences was extracted for each subject and correlated to memory performance.ResultIn our sample, 14 CAA subjects were classified as “amnestic”, and 15 as “non‐amnestic”. Amnestic and non‐amnestic subjects did not differ in age, education, or sex representation. Groups did not differ on any MRI markers of small vessel disease, nor in total brain volume (p&gt;0.05, for all). However, amnestic subjects showed smaller hippocampal volume (F(1,28)=5.65, p&lt;0.05). Voxel‐wise comparison of DVR [11C]‐PiB maps did not reveal any differences between amnestic and non‐amnestic CAA. Comparison of SUVR [18F]‐AV‐1451 maps revealed significant increase in tau PET binding in several regions for amnestic subjects (Figure 1). Mean tau PET binding in these regions was correlated with memory performance (r=‐0.68, p&lt;0.001), and hippocampal volume (r=‐0.44, p&lt;0.05), after accounting for age.ConclusionAmnestic CAA subjects present higher tau PET binding, and smaller hippocampal volume than non‐amnestic CAA. Our results suggest that memory impairments in CAA are related to tau pathology and medial temporal lobe neurodegeneration, consistent with the presence of concomitant AD.

Magnetic resonance imaging subtypes in subjective cognitive decline

AbstractBackgroundOlder adults who do not meet clinical criteria for mild cognitive impairment (MCI) or dementia, but who report progressive change in their cognitive abilities (i.e. subjective cognitive decline, SCD) are at increased risk for developing Alzheimer’s disease (AD). However, SCD can be associated to other conditions and its heterogeneity needs to be investigated further. In patients with AD dementia, data‐driven approaches to biological information have been useful in disentangling heterogeneity. We therefore utilized a data‐driven clustering method on regional structural magnetic resonance imaging (MRI) data to identify subtypes of SCD.MethodCognitively normal adults with SCD (n=86) and without SCD (n=68) from the AIBL cohort were studied. Clusters of SCD were determined based on 82 cortical and subcortical grey matter volumes using random forest pairwise similarity, multidimensional scaling, and distance‐based hierarchical clustering. The number of clusters was decided according to Carlinski‐Harabasz index. We also studied neuroanatomical, clinical, cognitive, and genetic characteristics at baseline, and clinical and cognitive progression over 7.5 years of follow‐up.ResultsThe data driven analyses yielded four SCD subtypes. The largest proportion (49%) showed regional volumes equivalent to those without SCD. Nonetheless, this group could be divided into two subtypes depending on the volume of the thalamus (no atrophy + low thalamic volume, 35%; and no atrophy + high thalamic volume, 15%). We also identified a Hippocampal‐sparing SCD subtype (32%), which displayed reduced cortical volumes but normal volume of the hippocampus; and a Diffuse SCD subtype (16%), which displayed reduced volume in both the hippocampus and cortical regions. Diffuse, Hippocampal‐sparing, and no atrophy + low Thalamic volume SCD subtypes were each associated with increased risk for MCI or dementia over 7.5 years, and showed faster decline in MMSE. The Diffuse SCD subtype was also characterized by an increased amyloid‐PET burden, small vessel disease (white matter hypointensities), and worse CDR scores at baseline.ConclusionsData‐driven analyses of structural MRI data revealed that SCD characterized by a Diffuse, Hippocampal‐sparing, or no atrophy with a low Thalamic volume pattern were at increased risk for MCI or dementia. Thus, these data‐driven methods show great potential for disentangling biological heterogeneity within SCD.

Subjective cognitive decline is associated with neurocognition in the SOL‐INCA study

AbstractBackgroundSubjective cognitive decline (SCD) is the experience of cognitive decline not yet apparent through formal neuropsychological testing. SCD is required to meet clinical criteria for mild cognitive impairment (MCI) and is a potential early risk marker of neurocognitive changes. Despite increased risk of cognitive decline in US Hispanics/Latinos, SCD research in this group is lacking. We investigated if SCD is cross‐sectionally associated with objective neurocognitive performance in SOL‐INCA, a large community‐based sample of diverse Hispanics/Latinos.MethodParticipants (N=5,282) were age 50+ and without reported dementia. The Everyday Cognition Short Form (ECog‐12) scale measured SCD. A global score, as well as memory and executive ECog‐12 sub‐scale scores, were calculated by averaging across z‐scores of individual items assessing memory and executive functional abilities (all items were averaged for the global score). Objective neurocognitive function was measured with tests of memory (Spanish English Verbal Learning Test‐Sum and Recall scores) and executive functions (word fluency, Trail Making Test A &amp; B, and Digit Symbol Substitution scores). Memory, executive, and global neurocognitive composite scores were created by averaging across z‐scores for each cognitive domain listed above, and across all tests for the global composite. Regression models interrogated associations of ECog‐12 (global and sub‐scale scores) with their respective objective neurocognitive function counterparts (global cognition, memory, and executive function neurocognitive composite scores), adjusting for age, sex, education, Hispanic/Latino background, depression, anxiety, and cardiovascular risk factors.ResultWomen comprised 53% of the sample and 25% of the sample were age 70+. Global score, memory, and executive sub‐scale ECog‐12 scores were significantly associated with global (B= ‐0.14), memory (B= ‐0.11), and executive function (B= ‐0.11) neurocognitive composite scores respectively (all p‐values &lt;.001), such that higher ECog‐12 scores (more complaints) were related to lower neurocognition for all three neurocognitive composites.ConclusionContrary to previous research in non‐Hispanic Whites, SCD is associated with concurrent objective neurocognitive function among Hispanic/Latino community‐dwelling adults. SCD may have utility as an early risk marker in this population. More research is needed to determine the predictive value of SCD reporting within Hispanics/Latinos as well as the utility of informant’s report in predicting neurocognitive change.

Diagnostic rates and amyloid positivity vary by definition of mild cognitive impairment

AbstractBackgroundThe concept of mild cognitive impairment (MCI) has evolved, and various approaches are used to classify MCI. Conventional MCI criteria, such as those used in the Alzheimer’s Disease Neuroimaging Initiative (ADNI), rely on a single memory test to detect objective cognitive impairment. Actuarial neuropsychological criteria for MCI that incorporate comprehensive neuropsychological performance have been proposed to balance sensitivity and reliability. We applied both actuarial and conventional criteria to a sample of non‐demented older adults. Resulting groups were compared on diagnostic rates and amyloid positivity.Method51 cognitive normal (CN) and 62 MCI participants from the Center for Neurodegeneration and Translational Neuroscience were previously classified by a diagnostic consensus review. Actuarial criteria required impairment (&gt;1 SD below means) on at least 2 tests within a cognitive domain. Conventional criteria were a modified version of ADNI criteria and required Mini Mental State Exam scores ≥ 24 and different cutoffs for Logical Memory based on education. Amyloid positron emission tomography (PET) determined amyloid status.ResultActuarial criteria classified 58 CN and 55 MCI, resulting in 77% agreement with consensus diagnosis. Conventional criteria diagnosed 36 CN and 77 MCI, resulting in 62% agreement with consensus diagnosis. McNemar tests indicated that the proportion of CN and MCI diagnoses were not significantly different between the actuarial and consensus (p=.23) but were significantly different between the conventional and consensus classifications (p=.03), with a 25% false positive rate for the conventional criteria. Chi‐squares demonstrated amyloid positivity was higher in MCI compared to CN for both the actuarial criteria (χ2(1)=31.16, p&lt;.001, Φ=.54) and conventional criteria (χ2(1)=4.71, p=.03, Φ=.21). However, actuarial MCI was twice as likely to be amyloid‐positive than amyloid‐negative (Figure 1), whereas conventional MCI showed similar frequencies of amyloid‐positive and amyloid‐negative status (Figure 2).ConclusionComparisons between MCI diagnostic methods found higher agreement between actuarial criteria and consensus diagnosis versus conventional criteria, which tended to over‐diagnose MCI. A stronger association between amyloid positivity and MCI diagnosis was found using actuarial criteria. Findings support the use of comprehensive neuropsychological criteria to increase the accuracy of identifying individuals with MCI who are at risk for AD dementia.

Extracellular complex of beta‐amyloid with glyceraldehyde‐3‐phosphate dehydrogenase contributes to neurodegeneration in Alzheimer’s disease

AbstractBackgroundThe discovery of migrating protein complexes armed with β‐amyloid (Aβ) and acting as the driving force of Alzheimer’s disease (AD) mechanism led us to suggest that besides the pathogenic peptide some other proteins may cooperate with the latter and enhance its cytotoxicity and intercellular propagation. One of such proteins was suggested to be glyceraldehyde‐3‐phosphatedehydrogenase (GAPDH), enzyme that in normal conditions maintains cellular glycolysis and under action of oxidative stress is converted to monomers and dimers and forms tight, insoluble complexes with aggregation‐prone polypeptides.MethodCSF samples were collected from patients of both genders. The cohort comprised four patient groups: (1) mild cognitive impairment (MCI) n = 21; (2) mild AD‐type dementia (‘Mild’), n = 58; (3) moderate AD‐type dementia (‘Moderate’) n = 57; and (4) severe AD‐type dementia (‘Severe’), n = 56. The diagnosis was established according to the NINCDS‐ARDRA criteria for AD and the Petersen criteria for MCI. Patients were assigned to severity subgroups based on their scores on the Mini‐Mental State Examination (MMSE). Two animal models of AD were used in this study: (1) “chemical” model in rats and (2) transgenic 5XFAD mice.ResultGAPDH is present in cerebrospinal fluid samples of AD patients as covalent complex with Aβ, and the heavier the stage of the disease, the higher is the level of such complexes. The increase of constitutional GAPDH level in AD animal models results in aggravation of cognitive and brain deficits linked to AD progression.ConclusionThe findings imply a potential role of GAPDH as biomarker and prerequisite of massive neuronal death on the late stages of Alzheimer’s disease Supported by RSF grant #19‐74‐30007.

Abstract 14215: Cognitive Impairment in Adult Congenital Heart Disease Survivors: A Pilot Study

Introduction: The most common comorbidities in children with congenital heart disease (CHD) are neurodevelopmental and psychosocial impairments, particularly in areas of executive function, memory, attention, and behavioral control. Limited studies in the adult CHD population suggest similar impairments exist and adults with CHD may be at increased risk for dementia. No studies have screened specifically for mild cognitive impairment and dementia in adult CHD patients. Methods: We performed a prospective cross-sectional study of adult CHD patients, ages 30-65 years, who were coming for routine clinic visits. We administered the Mini-Mental State Exam (MMSE) and scores were compared with population norms adjusted by age and education level. We also evaluated the association of MMSE scores with CHD complexity, demographic and clinical risk factors. Results: A total of 125 patients were recruited (55% male). The median age was 40 years (range 30-65). Almost all participants (97%) had a high school degree and 75% had some college education or advanced degrees. The majority of patients (94%) had moderate or complex CHD. Adjusting for age and education, CHD participants scored significantly lower than the general population (median 1 point lower, p=0.001). The greatest impairments occurred in recall and orientation. Factors associated with lower scores included decreased systemic ventricular function (p=0.028) and having ≥2 cardiac catheterizations (p=0.006). Five percent of the total cohort met the general threshold for mild cognitive impairment (MMSE&lt;24). Clinical factors associated with this degree of cognitive impairment were duration of cyanosis (p=0.005) and decreased systemic ventricular function (p=0.003). Conclusions: Our pilot study showed that, when adjusted for age and education level, adult CHD patients had significantly lower MMSE scores than the general population, with 5% meeting criteria for mild cognitive impairment. These findings suggest that subtle and early neurodevelopmental changes are present in the adult CHD population. Further studies are needed to investigate those changes and evaluate potential disease modifying therapies that might influence long-term outcomes in the adult CHD population.

Predictive and diagnostic utility of brief neuropsychological assessment in detecting Alzheimer's pathology and progression to dementia.

Objective: To assess the role of brief neuropsychological assessments in prediction and identification of Alzheimer's disease (AD) pathology and progression to AD dementia. Method: Adults (N = 255; range = 40-81 years) with self-reported cognitive decline underwent baseline and 2-year follow-up clinical assessment, including a brief neuropsychological screening and lumbar puncture. Five different mild cognitive impairment (MCI) algorithms were applied on baseline cognitive test results: one conventional, three amnestic (lenient, stringent, multidomain), and one comprehensive criterion. We compared predictive and diagnostic accuracy of these MCI criteria by performing logistic regression analyses and calculating diagnostic accuracy measures for 2-year outcomes of (1) clinical diagnosis of AD dementia and (2) cerebrospinal fluid biomarkers in the Alzheimer's continuum. Results: The lenient amnestic MCI criterion showed the largest effect size for predicting progression to AD dementia (OR = 13.762, 99% CI = 1.969-96.194, p = .001) and AD biomarkers (OR = 4.855, 99% CI = 1.974-11.924, p < .001) after 2 years. This criterion was sensitive for progression to dementia (sensitivity = 92.0%, specificity = 54.8%, positive likelihood ratio [LR+] = 2.03, LR- = 0.15) and showed the highest overall diagnostic accuracy for AD biomarkers (sensitivity = 72.7%, specificity = 59.1%, LR+ = 1.78, negative likelihood ratio [LR-] = 0.46). The multidomain amnestic MCI criterion produced the highest specificity for dementia (sensitivity = 76.0%, specificity = 73.0%, LR+ = 2.82, LR- = 0.33) and AD biomarkers (sensitivity = 46.8% specificity = 70.9% LR+ = 1.61, LR- = 0.75). Conclusions: Defining MCI using a brief neuropsychological battery provided limited accuracy for progression to AD dementia and cerebrospinal fluid Aβ. The lenient amnestic MCI criterion identified the highest number of individuals who progressed to clinical AD or showed biomarker pathology, but this approach included a substantial number of false positives. (PsycInfo Database Record (c) 2020 APA, all rights reserved).