Deficits In Mild Cognitive Impairment Research Articles

The role of olfactory dysfunction in mild cognitive impairment and Alzheimer's disease: A meta-analysis

PurposeThis comprehensive meta-analysis investigates the association between olfactory deficits in mild cognitive impairment (MCI) and Alzheimer's disease (AD). MethodsA thorough search across databases identified articles analyzing olfactory status in MCI or AD patients. Methodological quality assessment followed PRISMA guidelines. Hedges' g effect size statistic computed standard mean differences and 95% confidence intervals. Moderator analysis was conducted. ResultsAmong the included studies (65 for MCI and 61 for AD), odor identification exhibited larger effect sizes compared to odor threshold and discrimination, in both MCI and AD samples. Moderate effect size is found in OI scores in MCI (k = 65, SE = 0.078, CI 95% = [-1.151, -0.844]). Furthermore, compared to MCI, AD had moderate to large heterogeneous effects in olfactory identification (k = 61, g = -2.062, SE = 0.125, CI 95% = [-2.308, -1.816]). Global cognitive status is positively related to olfactory identification impairment in both MCI (k = 57, Z = 2.74, p = 0.006) and AD (k = 53, Z = 5.03, p < 0.0001) samples. ConclusionOlfactory impairments exhibit a notable and substantial presence in MCI. Among these impairments, odor identification experiences the greatest decline in MCI, mirroring the primary sensory deficit observed in AD. Consequently, the incorporation of a straightforward odor identification test is advisable in the evaluation of individuals vulnerable to the onset of AD, offering a practical screening tool for early detection.

Identification of Hippocampal and Amygdala Subfields Predictive of MoCA Scores in Patients with Dementia with Lewy Bodies

AbstractBackgroundHippocampal and amygdala subfields variably affect cognitive impairment in neurodegenerative diseases. Subfields of these regions can be well segmented using modern neuroimaging tools but their role in neurodegenerative disease is under active investigation. In this study, we identified hippocampal and amygdala subregions predictive of cognitive performance and motor symptoms severity measured by MoCA (Montreal Cognitive Assessment) and MDS‐UPDRS III, respectively, in patients with dementia with Lewy Bodies (DLB).MethodWe selected all participants with probable DLB (N = 48, mean age = 71±7 years, 15% female) enrolled in the Dementia with Lewy Bodies Consortium (DLBC) as of July 2022, with concurrent measures of 3D T1 MRI sequence, MoCA, and MDS‐UPDRS III scores. We performed cortical reconstruction and volumetric segmentation of hippocampal subfields and nuclei of the amygdala using FreeSurfer (v 7.2). We used combat harmonization to account for site and scanner differences. We trained and applied a bootstrapped, bidirectional stepwise regression model of 29 predictor variables comprised of sub‐fields and mean cortical thickness against MoCA and MDS‐UPDRS III, respectively, with an 80‐20 train‐test split ratio, and 5000 repetitions, corrected for age and sex.ResultSubfield segmentation is shown in Figure 1A. The best fitting model for MoCA included mean cortical thickness, parasubiculum, hippocampal and amygdala transition area, corticoamygdaloid transition area, and CA3 body (Figure 1B, adjusted R2 = 0.51). The best fitting model for MDS‐UPDRS III included the cortical nucleus of the amygdala and CA1 body (Figure 1C, adjusted R2 = 0.22). This model was considered a poor fit. We considered MoCA for further analysis and closely predicted scores in our 20% partitioned test sample (Figure 2A, R2 = 0.38).ConclusionWe report model‐based selection of hippocampal and amygdala subfields to predict MoCA scores in DLB. Atrophy in these regions has been associated with global cognitive deficit in mild cognitive impairment and Alzheimer disease cohorts. The model fit for MDS‐UPDRS III scores was poor, providing evidence that these brain regions do not serve a role in motor control.

High-Frequency rTMS Could Improve Impaired Memory in Mild Cognitive Impairment Patients in China: A Randomized Controlled Study.

The purpose of this study was to investigate the effects of repetitive transcranial magnetic stimulation (rTMS) on improving memory deficits in mild cognitive impairment (MCI), as well as to provide visualized evidence for neuronal specificity by using resting-state functional magnetic resonance imaging. Forty MCI patients were enrolled to receive 10-session and sham-controlled 10Hz-rTMS over the left dorsolateral prefrontal cortex. The resting-state functional magnetic resonance imaging combined with memory scales assessment were performed before and after the intervention. To elucidate the therapeutic mechanism of rTMS, amplitude of low-frequency fluctuations (ALFF) and functional connectivity were calculated. The Pearson correlation was used to measure the relationship between ALFF and memory performance. Compared with the sham group, ALFF significantly increased in the right insula, right inferior frontal gyrus-opercular part, and decreased in the left middle occipital gyrus, left angular gyrus, and left lingual gyrus after rTMS. The change in Auditory Verbal Learning Test scores were negatively correlated with ALFF decreases in the left lingual gyrus. Functional connectivity significantly increased between the posterior cingulate cortex and right supramarginal gyrus, and decreased between the right frontoinsular cortex and right supramarginal gyrus after intervention. High-frequency rTMS over the left dorsolateral prefrontal cortex could facilitate improvement on impaired memory in patients with MCI via modulating the neuronal activity and brain network.

Topological changes of fast large-scale brain dynamics in mild cognitive impairment predict early memory impairment: a resting-state, source reconstructed, magnetoencephalography study

Functional connectivity has been used as a framework to investigate widespread brain interactions underlying cognitive deficits in mild cognitive impairment (MCI). However, many functional connectivity metrics focus on the average of the periodic activities, disregarding the aperiodic bursts of activity (i.e., the neuronal avalanches) characterizing the large-scale dynamic activities of the brain. Here, we apply the recently described avalanche transition matrix framework to source-reconstructed magnetoencephalography signals in a cohort of 32 MCI patients and 32 healthy controls to describe the spatio-temporal features of neuronal avalanches and explore their topological properties. Our results showed that MCI patients showed a more centralized network (as assessed by higher values of the degree divergence and leaf fraction) as compared to healthy controls. Furthermore, we found that the degree divergence (in the theta band) was predictive of hippocampal memory impairment. These findings highlight the role of the changes of aperiodic bursts in clinical conditions and may contribute to a more thorough phenotypical assessment of patients.

Decreased GABA levels of the anterior and posterior cingulate cortex are associated with executive dysfunction in mild cognitive impairment.

Executive function impairment, a slight but noticeable cognitive deficit in mild cognitive impairment (MCI) patients, is influenced by gamma-aminobutyric acid (GABA) levels. Reduced cognitive function is accompanied by thinning of the cerebral cortex, which has higher GABA levels than white matter. However, the relationships among GABA levels, cortical thickness, and executive function in MCI patients have not yet been elucidated. We investigated the relationships among GABA levels, cortical thickness, and executive function in MCI patients. In this study, a total of 36 MCI patients and 36 sex-, age-, and education-matched healthy controls (HC) were recruited. But 33 MCI patients and 35 HC were included because of head motion or poor data quality for three MCI patients and one HC. The levels of gamma-aminobutyric acid plus relative to creatine (GABA+/Cr) and glutamate-glutamine relative to creatine (Glx/Cr) in the anterior cingulate cortex (ACC) and posterior cingulate cortex (PCC) were measured using the Meshcher-Garwood point resolved spectroscopy (MEGA-PRESS) sequence. Metabolite ratios, cortical thickness, and executive function and their interrelationships were determined in the MCI and HC groups. Patients with MCI showed lower GABA+/Cr levels in the ACC and PCC. Combined levels of GABA+ and Glx in the ACC and GABA+ in the PCC showed good diagnostic efficacy for MCI (AUC: 0.82). But no differences in cortical thickness were found between the two groups. In the MCI group, lower GABA+/Cr level was correlated to worse performance on the digit span test backward, and the shape trail test-B. The cortical thickness was not associated with GABA+ levels and executive function in patients. These results implied that decreased GABA levels in the ACC and PCC had a critical role in the early diagnosis of impaired executive function of MCI. Therefore, GABA in the ACC and PCC could be a potential diagnostic marker of the executive function decline of MCI.

Working Memory Precision and Associative Binding in Mild Cognitive Impairment

ABSTRACT To better understand working memory (WM) deficits in Mild Cognitive Impairment (MCI), we examined information precision and associative binding in WM in 21 participants with MCI, compared to 16 healthy controls, using an item-location delayed reproduction task. WM, along with other executive functions (i.e. Trail Making Task (TMT) and Stroop task), were measured before and after a 2-h nap. The napping manipulation was intended as an exploratory element to this study exploring potential impacts of napping on executive functions. Compared to healthy participants, participants with MCI exhibited inferior performance not only in identifying encoded WM items but also on item-location associative binding and location precision even when only one item was involved. We also found changes on TMT and Stroop tasks in MCI, reflecting inferior attention and inhibitory control. Post-napping performance improved in most of these WM and other executive measures, both in MCI and their healthy peers. Our study shows that associative binding and WM precision can reliably differentiate MCIs from their healthy peers. Additionally, most measures showed no differential effect of group pre- and post-napping. These findings may contribute to better understanding cognitive deficits in MCI therefore improving the diagnosis of MCI.

DUAL-TASK TRAINING FOR IMPROVING COGNITIVE-MOTOR INTERFERENCE

Abstract Dr. Bhatt will discuss the differences in types of cognitive motor interference patterns experienced for different tasks (gaitand volitional versus reactive balance) in cognitively intact versus people with mild cognitive impairment. She will discuss the effectiveness of dual-task training and exergaming on gait, volitional and reactive balance control in older adults with mild cognitive impairment. After 4 weeks of such training, the results showed beneficial effects on improving volitional based performance when performed with a cognitive task (i.e., spatial memory and executive function) and had significant improvement in NIH toolbox (cognitive- increased working memory, episodic memory and executive function, and motor-increased gait speed). However, its positive effects on dual task reactive balance control were limited. Additionally, the speaker will go on to discuss the associations of balance control deficits in mild cognitive impairment with neural correlates (structural and functional brain integrity) to understand the attributing factors to increased fall risk in people with mild cognitive impairment.

УМЕРЕННЫЕ КОГНИТИВНЫЕ НАРУШЕНИЯ В ПРАКТИКЕ ВРАЧА-НЕВРОЛОГА

Cognitive impairment and dementia are an relevant problem of modern neurology and psychiatry, which is explained by their wide prevalence, as well as the predicted increase in the number of patients in the future. However, dementia in most cases does not occur acutely, its development is preceded by a long period when cognitive impairments do not disrupt the patient’s everyday and professional life yet. Such cognitive impairments are called “pre-dementia” and are divided into subjective, subtle, and mild. With subjective cognitive impairment, patients present complaints; however, neuropsychological testing does not reveal decreased cognitive functions. Subtle cognitive impairment is accompanied by a decrease in cognitive functions when using highly sensitive scales. This article provides an overview of current data on the definition, classification, diagnosis, and treatment of mild cognitive impairment (MCI) from the point of view of the evidence-based medicine for timely diagnostics of the state and its effective correction. In patients with MCI, in addition to complaints of cognitive deficit, it is detected during screening neuropsychological testing; but unlike dementia, it does not impair the patient’s functionality. MCI is a leading risk factor for future dementia. However, according to research, cognitive deficits can not only progress, but also stabilize and even regress. In this regard, it is important to identify patients with MCI on time, establish nosological affiliation for correcting risk factors and prescribing treatment. The most common causes of MCI can be neurodegenerative disorders (primarily Alzheimer’s disease) and cerebrovascular diseases. The authors present the diagnostic value of popular scales such as the Mini-Mental State Examination, the Montreal Cognitive Assessment Scale and the 3-CT test in the diagnosis of MCI. The possibilities of using biomarkers, such as the determination of beta-amyloid and tau-protein in the cerebrospinal fluid, and the detection of signs of neuronal damage during neuroimaging of the brain, are discussed. It is stated that the most proven methods of influencing cognitive deficits in MCI are non-drug measures.

Volume, density, and thickness brain abnormalities in mild cognitive impairment: an ALE meta-analysis controlling for age and education.

Prior meta-analyses have provided important information regarding which brain areas are structurally compromised in individuals with mild cognitive impairment (MCI). These studies have not however separated volume, density, and thickness, controlled for important demographic influences, considered null findings, or recognized studies indicating increased brain volumes in MCI individuals. Furthermore, there is a question as to whether deficits extend into cortical regions, and also into the thalamus. This study aims to address these issues using activation likelihood estimation (ALE) analyses with a sample size more than twice that of prior meta-analyses. A total of 71 studies were identified and entered into the ALE analysis which consisted of 2262 with MCI and 1902 healthy controls. Three major clusters were identified showing decreased gray matter volume in the MCI group compared to controls, with the most salient decreases being in the hippocampus, parahippocampal gyrus, and the amygdala. Reduced thalamic volume was also observed, but to a lesser extent. Density was reduced in the left hippocampus, while thickness was reduced in the uncus. No significant cluster emerged from an ALE meta-analysis of studies finding volume increases in MCI individuals. While the MCI group was significantly older and less educated than controls, controlling for these factors still resulted in significant, albeit attenuated findings. These results support hippocampal and parahippocampal deficits in MCI, and further highlight the amygdala, thalamus, and uncus as other areas to be considered in future MCI studies.

Age and Anterior Basal Forebrain Volume Predict the Cholinergic Deficit in Patients with Mild Cognitive Impairment due to Alzheimer's Disease.

Early and severe neuronal loss in the cholinergic basal forebrain is observed in Alzheimer's disease (AD). To date, cholinomimetics play a central role in the symptomatic treatment of AD dementia. Although basic research indicates that a cholinergic deficit is present in AD before dementia, the efficacy of cholinomimetics in mild cognitive impairment (MCI) remains controversial. Predictors of cholinergic impairment could guide individualized therapy. To investigate if the extent of the cholinergic deficit, measured using positron emission tomography (PET) and the tracer 11C-N-methyl-4-piperidyl acetate (MP4A), could be predicted from the volume of cholinergic basal forebrain nuclei in non-demented AD patients. Seventeen patients with a high likelihood of MCI due to AD and 18 age-matched cognitively healthy adults underwent MRI-scanning. Basal forebrain volume was assessed using voxel-based morphometry and a cytoarchitectonic atlas of cholinergic nuclei. Cortical acetylcholinesterase (AChE) activity was measured using MP4A-PET. Cortical AChE activity and nucleus basalis of Meynert (Ch4 area) volume were significantly decreased in MCI. The extent of the cholinergic deficit varied considerably across patients. Greater volumes of anterior basal forebrain nuclei (Ch1/2 area) and younger age (Spearman's rho(17) = -0.596, 95% -CI [-0.905, -0.119] and 0.593, 95% -CI [0.092, 0.863])) were associated with a greater cholinergic deficit. Data suggest that less atrophy of the Ch1/2 area and younger age are associated with a more significant cholinergic deficit in MCI due to AD. Further investigations are warranted to determine if the individual response to cholinomimetics can be inferred from these measures.

Improved functional connectivity after a 6‐month ketogenic supplementation in mild cognitive impairment

AbstractBackgroundKetones, the brain’s alternative fuel to glucose, bypass the brain glucose deficit in mild cognitive impairment (MCI). The BENEFIC trial conducted in MCI showed improved measures of cognition in multiple domains after a 6‐month ketogenic intervention [Fortier et al. 2019]. Functional connectivity in the dorsal‐attention network (DAN) deteriorates early in MCI, and prior to changes in the ventral‐attention network [Zhang et al. 2015]. We aimed to assess whether improved cognitive outcomes in the BENEFIC Trial were linked to improved brain functional connectivity.MethodParticipants in this 6‐month intervention were randomized to a placebo (n= 15) or ketogenic medium chain triglyceride (kMCT; n= 17) drink. A neurocognitive battery and brain imaging were performed pre‐ and post‐intervention. Functional connectivity was computed from resting‐state functional magnetic resonance images. Independent component analysis (FSL Melodic) was used to segment seven major resting‐state networks (DAN, ventral‐attention, frontoparietal, limbic, somatomotor, default‐mode and visual) [Yeo et al. 2011]. Regional cortical ketone (11C‐acetoacetate) and glucose (18F‐fluorodeoxyglucose) metabolic rates were also quantified using positron emission tomography (PET).ResultChanges (post ‐ pre) in DAN functional connectivity was significantly higher in the kMCT group vs placebo (P= 0.024). After correction for age, sex, education, ApoE status and intracranial volume, the significant difference between groups was still present, with a large effect size (partial h2= 0.16; P= 0.043; Figure 1). Connectivity in no other networks was significantly different between groups. Changes in attention and processing speed composite Z‐score (r= 0.42; P= 0.021) and specific tests targeting attention (Trail Making visual scanning and number sequencing conditions) were significantly associated with the increased DAN functional connectivity. Change in ketone uptake specifically in DAN cortical regions (Figure 2C) was significantly higher in the kMCT vs placebo group (P= 0.001) and was directly associated with the improved DAN functional connectivity, with a large effect size (r= 0.69; P= 0.002; Figure 3).ConclusionWe show that a 6‐month ketogenic intervention improves DAN functional connectivity in MCI, an improvement that is directly linked to increased energy (ketone) supply to the DAN. The beneficial effect of ketones on cognition in MCI may be linked to improved DAN connectivity.

Functional Integrity of Executive Control Network Contributed to Retained Executive Abilities in Mild Cognitive Impairment.

Background: Mild cognitive impairment (MCI) is considered to be a transitional state between normal aging and Alzheimer's dementia (AD). Recent studies have indicated that executive function (EF) declines during MCI. However, only a limited number of studies have investigated the neural basis of EF deficits in MCI. Herein, we investigate the changes of regional brain spontaneous activity and functional connectivity (FC) of the executive control network (ECN) between high EF and low EF groups.Methods: According to EF composite score (ADNI-EF) from the Alzheimer's Disease Neuroimaging Initiative (ADNI), we divided MCI into two groups, including the MCI-highEF group and MCI-lowEF group. Resting-state functional MRI was utilized to investigate the fractional amplitude of low-frequency fluctuation (fALFF) and ECN functional connectivity across 23 healthy controls (HC), 11 MCI-highEF, and 14 MCI-lowEF participants. Moreover, a partial correlation analysis was carried out to examine the relationship between altered fALFF or connectivity of the ECN and the ADNI-EF.Results: Compared to HC, the MCI-highEF participants demonstrated increased fALFF in the left superior temporal gyrus (STG), as well as decreased fALFF in the right precentral gyrus, right postcentral gyrus, and left middle frontal gyrus (MFG). The MCI-lowEF participants demonstrated increased fALFF in the cerebellar vermis and decreased fALFF in the left MFG. Additionally, compared to HC, the MCI-highEF participants indicated no significant difference in connectivity of the ECN. Furthermore, the MCI-lowEF participants showed increased ECN FC in the left cuneus and left MFG, as well as decreased ECN functional connectivity in the right parahippocampal gyrus (PHG). Notably, the altered fALFF in the left MFG was positively correlated to ADNI-EF, while the altered fALFF in cerebellar vermis is negatively correlated with ADNI-EF across the two MCI groups and the HC group. Altered ECN functional connectivity in the right PHG is negatively correlated to ADNI-EF, while altered ECN functional connectivity in the left cuneus is negatively correlated to ADNI-EF across the three groups.Conclusions: Our current study demonstrates the presence of different patterns of regional brain spontaneous activity and ECN FC in the MCI-highEF group and MCI-lowEF group. Furthermore, the ECN FC of the MCI-highEF group was not disrupted, which may contribute to retained EF in MCI.

Cognitive and Neuroimaging Profiles of Older Adults With Attention Deficit/Hyperactivity Disorder Presenting to a Memory Clinic

Objective: Some features of attention-deficit/hyperactivity disorder (ADHD) may resemble those of mild cognitive impairment (MCI) in older adults, contributing to diagnostic uncertainty in individuals seeking assessment in memory clinics. We systematically compared cognition and brain structure in ADHD and MCI to clarify the extent of overlap and identify potential features unique to each. Method: Older adults from a Cognitive Neurology clinic (40 ADHD, 29 MCI, 37 controls) underwent neuropsychological assessment. A subsample (n = 80) underwent structural neuroimaging. Results: Memory was impaired in both patient groups, but reflected a storage deficit in MCI (supported by relatively smaller hippocampi) and an encoding deficit in ADHD (supported by frontal lobe thinning). Both groups displayed normal executive functioning. Semantic retrieval was uniquely impaired in MCI. Conclusion: Although ADHD has been proposed as a dementia risk factor or prodrome, we propose it is rather a pathophysiologically-unique phenotypic mimic acting via overlap in memory and executive performance.

Amnestic MCI in ADNI: Maybe Not Enough Memory Impairment?

Mild cognitive impairment (MCI), especially the amnestic subtype, has been proposed as a prodromal phase of Alzheimer disease (AD), where the patient has memory deficits but no/minimal functional impairment.1 Clinically, the demarcation point for memory deficits in MCI has typically been 1–1.5 SD units below normative data.1,2 Much of what we know about MCI has come from findings from the Alzheimer's Disease Neuroimaging Initiative (ADNI) studies.3

Executive function deficits in mild cognitive impairment: evidence from saccade tasks

Objectives: Early detection of mild cognitive impairment (MCI) is necessary to prevent irreversible brain damage caused by incipient Alzheimer’s disease. It has been showing that amnestic MCI (a-MCI) subjects exhibit subtle deficits in executive function that can be tested using saccade eye movements. Eye-tracking technology is a sensitive method to measure cognitive impairments in dementia and MCI. Methods In this study, we used eye-tracking technology to explore saccade impairments to distinguish between a-MCI and the variants of reference controls. 21 patients with AD, 40 patients with a-MCI, and 59 normal participants were recruited in current study. We measured saccade reaction time, saccade errors, saccade omission, and uncorrected saccades using anti-saccade and pro-saccade tasks with ‘gap’ and ‘overlap’ procedures. These parameters were used as markers of executive function and visual attention deficits.Results: The findings revealed that more errors, more omissions, and fewer corrections characterized the saccade behavior of the a-MCI group compared to the reference group. These eye-tracking characteristics can be considered as inhibitory control and working memory deficits in a-MCI subjects. Our results thus demonstrate the applicability of the anti-saccade task as a cognitive marker in a-MCI. Conclusion The work provides further support for eye-tracking as a useful diagnostic biomarker in the assessment of executive function in aging with cognitive impairments.

Effects of Mental Imagery on Prospective Memory: A Process Analysis in Individuals with Amnestic Mild Cognitive Impairment

Introduction: Prospective memory (PM) is a multiphasic cognitive function important for autonomy and functional independence but is easily disrupted by pathological aging processes. Through cognitive simulation of perceptual experiences, mental imagery could be an effective compensatory strategy to enhance PM performance. Nevertheless, relevant research in individuals with amnestic mild cognitive impairment (MCI) has been limited, and the underlying mechanism of the therapeutic effect has not been sufficiently elucidated. The present study aimed to examine complex PM performances and the effect of mental imagery on each phase in older adults with MCI and to investigate the underlying cognitive mechanism from a process perspective. Methods: Twenty-eight MCI and 32 normal aging controls completed a seminaturalistic PM task, in addition to a series of neuropsychological tests. Participants from each group were randomly assigned to a mental imagery condition or a standard repeated encoding condition before performing the PM task. Four indices were used to measure performance in the intention formation, intention retention, intention initiation, and intention execution phases of PM. Performances in each phase was compared between the 2 diagnostic groups and the 2 instruction conditions. Results: The MCI group performed worse than the normal aging group in the intention formation and intention retention phases. The participants in the mental imagery condition performed significantly better than those in the standard condition during the intention formation, intention retention, and intention execution phases, regardless of the diagnostic group. Moreover, there was a significant interaction between the group and condition during intention retention, showing that people with MCI benefited even more from mental imagery than normal aging in this phase. Performance in the intention retention phase predicted performance in the intention initiation and intention execution phases. Discussion: PM deficits in MCI mainly manifest during planning and retaining intentions. Mental imagery was able to promote performance in all but the initiation phase, although a trend for improvement was observed in this phase. The effects of mental imagery may be exerted in the intention retention phase by strengthening the PM cue-action bond, thereby facilitating the probability of intention initiation and bolstering fidelity to the original plan during intention execution.

Emotional Processing in Healthy Ageing, Mild Cognitive Impairment, and Alzheimer's Disease.

Emotional processing, particularly facial expression recognition, is essential for social cognition, and dysfunction may be associated with poor cognitive health. In pathological ageing conditions, such as mild cognitive impairment (MCI) and Alzheimer’s disease (AD), in which cognitive impairments are present, disturbed emotional processing and difficulty with social interactions have been documented. However, it is unclear how pathological ageing affects emotional processing and human social behaviour. The aim of this study is to provide insight into how emotional processing is affected in MCI and AD and whether this capacity can constitute a differentiating factor allowing the preclinical diagnosis of both diseases. For this purpose, an ecological emotional battery adapted from five subsets of the Florida Affect Battery was used. Given that emotion may not be separated from cognition, the affect battery was divided into subtests according to cognitive demand, resulting in three blocks. Our results showed that individuals with MCI or AD had poorer performance on the emotional processing tasks, although with different patterns, than that of controls. Cognitive demand may be responsible for the execution patterns of different emotional processing tests. Tasks with moderate cognitive demand are the most sensitive for discriminating between two cognitive impairment entities. In summary, emotional processing tasks may aid in characterising the neurocognitive deficits in MCI or AD. Additionally, identifying these deficits may be useful for developing interventions that specifically target these emotional processing problems.

Brainstem substructures and cognition in prodromal Alzheimer\u2019s disease

Neuropathological research suggests the tau pathology of Alzheimer’s disease may originate in brainstem nuclei, yet it remains unknown whether tau-mediated degeneration of brainstem nuclei influences cognitive impairment in prodromal Alzheimer’s disease. The present study examined cognitive domains impacted in prodromal Alzheimer’s disease and brainstem substructure volume in cognitively normal older adults (n = 814) and those with mild cognitive impairment (n = 542). Subsamples of cognitively normal (n = 112) and mild cognitive impairment (n = 202) also had cerebrospinal fluid Alzheimer’s disease biomarker characterization. Region-of-interest and voxel-level analyses related whole brainstem, midbrain, pons, and locus coeruleus volumes to cognition with multiple linear regression models corrected for age, sex, education, apolipoprotein-ε4 carrier status, and MRI magnet strength. Within mild cognitive impairment participants, smaller midbrain and locus coeruleus volumes were significantly related to poorer performance on tests of attention and executive function, and the relationship between locus coeruleus volume and executive abilities remained significant in the mild cognitive impairment subsample with biomarker-confirmed Alzheimer’s disease. A brainstem-masked voxel-wise regression further demonstrated an association between locus coeruleus volume and executive abilities. Brainstem volumes were not significantly related to memory processes. Study findings implicate midbrain and locus coeruleus volume in attention and executive deficits in mild cognitive impairment. Together with prior neuropathological studies, our data suggest a link between Alzheimer’s disease-related degeneration of brainstem nuclei and cognitive deficits in prodromal Alzheimer’s disease.

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.

Characterization of prospective memory in mild cognitive impairment by using the Ecological test of Prospective Memory

ABSTRACT The objective of this study was to explore the exact nature, extent, and cognitive correlates of prospective memory deficits in mild cognitive impairment (MCI) by using the Ecological Test of Prospective Memory (TEMP). Twenty-five MCI participants and 25 healthy older adults (HOA) performed the TEMP, the Envelope Task, the Comprehensive Assessment of Prospective Memory (CAPM), and a neuropsychological test battery. Results showed that, during the TEMP, MCI participants had difficulty detecting the moment to perform the intentions in the time-based condition (prospective component) and retrieving the associated actions in the event- and time-based conditions (retrospective component). The prospective component of the event-based condition was correlated with retrospective memory, whereas the prospective component of the time-based condition was correlated with executive functions. Finally, the TEMP yielded good sensitivity and specificity for discriminating between MCI and HOA, contrary to the Envelope Task and the CAPM.