Introduction This study investigates whether plasma biomarkers (Aβ42/40 and p‐tau 181), APS, as well as apolipoprotein E (APOE) proteotype predict cognitive deficits in elderly adults from the Democratic Republic of Congo. Methods Forty‐four with possible AD (pAD) and 41 healthy control (HC) subjects were screened using CSID and AQ, underwent cognitive assessment with the African Neuropsychology Battery (ANB), and provided blood samples for plasma Aβ42, Aβ40, Aβ42/40, and APOE proteotype. Linear and logistic regression were used to evaluate the associations of plasma biomarkers with ANB tests and the ability of biomarkers to predict cognitive status. Results Patients with pAD had significantly lower plasma Aβ42/40 levels, higher APS, and higher prevalence of APOE E4 allele compared to HC. Groups did not differ in levels of Aβ40, Aβ42, or P‐tau 181. Results showed that Aβ42/40 ratio and APS were significantly associated with African Naming Test (ANT), African List Memory Test (ALMT), and African Visuospatial Memory Test (AVMT) scores, while the presence of APOE E4 allele was associated with ANT, ALMT, AVMT, and APT scores. P‐tau 181 did not show any significant associations while adjusting for age, education, and gender. APS showed the highest area under the curve (AUC) value (AUC = 0.78, 95% confidence interval [CI]: 0.68–0.88) followed by Aβ42/40 (AUC = 0.75, 95% CI: 0.66–0.86) and APOE E4 (AUC = 0.69 (CI 0.57–0.81) in discriminating pAD from HC. Discussion These results demonstrate associations between select plasma biomarker of AD pathology (Aβ42/40), APS, and APOE E4 allele) and ANB test scores and the ability of these biomarkers to differentiate pAD from cognitively normal SSA individuals, consistent with findings reported in other settings.

Background: Alzheimer’s Disease (AD), the most common cause of dementia, poses a significant global burden. Diagnosis typically involves invasive and costly methods like neuroimaging or cerebrospinal fluid (CSF) biomarker testing of phosphorylated tau (p-tau) and amyloid-β42/40 (Aβ42/40). Such procedures are especially impractical in resource-constrained regions, such as the Democratic Republic of Congo (DRC). Blood-based biomarker testing may provide a more accessible screening opportunity. Objective: This study aims to examine if AD-related blood-based biomarkers are associated with cognitive test performance in the Congolese population, where limited research has been conducted. Methods: In this cross-sectional study of 81 Congolese individuals, cognitive assessments (Alzheimer’s Questionnaire (AQ) and Community Screening Interview for Dementia (CSID)) distinguished dementia cases from controls. Blood draws were taken to assess p-tau 181 and Aβ42/40 biomarkers. Relationships between the biomarkers and cognitive performance were analyzed using multiple linear regression models. Results: Lower plasma Aβ42/40 was significantly associated with lower CSID scores and higher AQ scores, indicative of AD (p<0.001). These relationships were observed in healthy controls (CSID p=0.01, AQ p=0.03), but not in dementia cases. However, p-tau 181 did not exhibit significant associations with either measure. Factors such as age, sex, education, presence of APOE e4 allele, did not alter these relationships. Conclusion: Understanding relationships between AD-related screening tests and blood-biomarkers is a step towards utilization of blood-based biomarker tests as a screening tool for AD, especially in resource-limited regions. Further research should be conducted to evaluate blood biomarker test efficacy in larger samples and other populations.

Objective To determine the impact of different aortic clamping strategies on the incidence of cerebral embolic events during coronary artery bypass grafting (CABG). Methods Between 2012 and 2015, 142 patients with low-grade aortic disease (epiaortic ultrasound grade I/II) undergoing primary isolated CABG were studied. Those undergoing off-pump CABG were randomized to a partial clamp (n = 36) or clampless facilitating device (CFD; n = 36) strategy. Those undergoing on-pump CABG were randomized to a single-clamp (n = 34) or double-clamp (n = 36) strategy. Transcranial Doppler ultrasonography (TCD) was performed to identify high-intensity transient signals (HITS) in the middle cerebral arteries during periods of aortic manipulation. Neurocognitive testing was performed at baseline and 30-days postoperatively. The primary endpoint was total number of HITS detected by TCD. Groups were compared using the Mann–Whitney U test. Results In the off-pump group, the median number of total HITS were higher in the CFD subgroup (30.0; interquartile range [IQR], 22-43) compared with the partial clamp subgroup (7.0; IQR, 0-16; P <.0001). In the CFD subgroup, the median number of total HITS was significantly lower for patients with 1 CFD compared with patients with >1 CFD (12.5 [IQR, 4-19] vs 36.0 [IQR, 25-47]; P =.001). In the on-pump group, the median number of total HITS was 10.0 (IQR, 3-17) in the single-clamp group, compared with 16.0 (IQR, 4-49) in the double-clamp group (P =.10). There were no differences in neurocognitive outcomes across the groups. Conclusions For patients with low-grade aortic disease, the use of CFDs was associated with an increased rate of cerebral embolic events compared with partial clamping during off-pump CABG. A single-clamp strategy during on-pump CABG did not significantly reduce embolic events compared with a double-clamp strategy.

Introduction Memory deficits characterize Alzheimer's dementia and the clinical precursor stage known as mild cognitive impairment. Nonpharmacologic interventions hold promise for enhancing functioning in these patients, potentially delaying functional impairment that denotes transition to dementia. Previous findings revealed that mnemonic strategy training (MST) enhances long-term retention of trained stimuli and is accompanied by increased blood oxygen level–dependent signal in the lateral frontal and parietal cortices as well as in the hippocampus. The present study was designed to enhance MST generalization, and the range of patients who benefit, via concurrent delivery of transcranial direct current stimulation (tDCS). Methods This protocol describes a prospective, randomized controlled, four-arm, double-blind study targeting memory deficits in those with mild cognitive impairment. Once randomized, participants complete five consecutive daily sessions in which they receive either active or sham high definition tDCS over the left lateral prefrontal cortex, a region known to be important for successful memory encoding and that has been engaged by MST. High definition tDCS (active or sham) will be combined with either MST or autobiographical memory recall (comparable to reminiscence therapy). Participants undergo memory testing using ecologically relevant measures and functional magnetic resonance imaging before and after these treatment sessions as well as at a 3-month follow-up. Primary outcome measures include face-name and object-location association tasks. Secondary outcome measures include self-report of memory abilities as well as a spatial navigation task (near transfer) and prose memory (medication instructions; far transfer). Changes in functional magnetic resonance imaging will be evaluated during both task performance and the resting-state using activation and connectivity analyses. Discussion The results will provide important information about the efficacy of cognitive and neuromodulatory techniques as well as the synergistic interaction between these promising approaches. Exploratory results will examine patient characteristics that affect treatment efficacy, thereby identifying those most appropriate for intervention.

Background: Mild cognitive impairment (MCI) is often a precursor to Alzheimer’s disease. Little research has examined the efficacy of cognitive rehabilitation in patients with MCI, and the relevant neural mechanisms have not been explored. We previously reported on a pilot study showing the behavioral efficacy of cognitive rehabilitation using mnemonic strategies for face-name associations in patients with MCI. Here we used functional magnetic resonance imaging (fMRI) to test whether there were training-specific changes in activation and connectivity within memory-related areas. Methods: Six patients with amnestic, multi-domain MCI underwent pre- and post-training fMRI scans, during which they encoded 90 novel face-name pairs, and completed a 4-choice recognition memory test immediately after scanning. Patients were taught mnemonic strategies for half the face-name pairs during three intervening training sessions. Results: Training-specific effects comprised significantly increased activation within a widespread cerebral cortical network involving medial frontal, parietal, and occipital regions, the left frontal operculum and angular gyrus, and regions in left lateral temporal cortex. Increased activation common to trained and untrained stimuli was found in a separate network involving inferior frontal, lateral parietal and occipital cortical regions. Effective connectivity analysis using multivariate, correlation-purged Granger causality analysis revealed generally increased connectivity after training, particularly involving the middle temporal gyrus and foci in the occipital cortex and the precuneus. Conclusion: Our findings suggest that the effectiveness of explicit memory training in patients with MCI is associated with training-specific increases in activation and connectivity in a distributed neural system that includes areas involved in explicit memory.

Learning and memory deficits characterize the diagnosis of amnestic mild cognitive impairment (aMCI), which is widely viewed as a clinical precursor to Alzheimer's type dementia. There is a growing interest in non-pharmacologic interventions, such as mnemonic strategies, for improving learning and memory in patients with aMCI as well as for maintaining functioning in healthy older adults. Using an ecologically relevant object-location association paradigm, we conducted a randomized, controlled, single-blind study in which healthy older adults and patients with aMCI were randomized to either mnemonic strategy training or a control group that was matched for stimulus exposure. We previously reported that mnemonic strategy training resulted in significantly greater learning and memory improvements compared to the matched exposure condition, in both aMCI patients and healthy controls. The current study examined changes in neocortical activation during encoding in a subset of participants who underwent functional magnetic resonance imaging (fMRI) scanning both before and after training. To minimize potential confounds in between-group comparisons, we employed non-linear cortex based alignment and included only correctly encoded stimuli in our analyses. When re-encoding stimuli learned during training (i.e., trained stimuli), we found a general enhancement of activation in right prefrontal and parietal regions, possibly reflecting practice-related improvement in coordinate spatial processing in all but the aMCI exposure group. Left hemisphere activation was typically only evident in the mnemonic strategy trained participants, regardless of diagnostic status, with the ventrolateral prefrontal cortex appearing especially important for strategy use. While encoding relatively novel stimuli, both mnemonic strategy groups (aMCI patients and healthy controls) demonstrated increased activation in a subset of regions showing change for the trained stimuli, indicating a mnemonic strategy-induced change in the processing of new information. These findings could not be explained by repeated exposure since there was little to no activation overlap in the respective exposure control groups. The current results reinforce the potential benefits of cognitive interventions in these growing populations and indicate that neuroplastic change in key rostral and lateral prefrontal regions mediate this behavioral change.

Learning and memory deficits typify patients with mild cognitive impairment (MCI) and are generally attributed to medial temporal lobe dysfunction. Although the hippocampus is perhaps the most commonly studied neuroanatomical structure in these patients, there have been few attempts to identify rehabilitative interventions that facilitate its functioning. Here, we present results from a randomized, controlled, single-blind study in which patients with MCI and healthy elderly controls (HEC) were randomized to either 3 sessions of mnemonic strategy training (MS) or a matched-exposure control group (XP). All participants underwent pre- and post-training fMRI scanning as they encoded and retrieved object-location associations. For the current report, fMRI analyses were restricted to the hippocampus, as defined anatomically. Before training, MCI patients showed reduced hippocampal activity during both encoding and retrieval, relative to HEC. Following training, the MCI MS group demonstrated increased activity during both encoding and retrieval. There were significant differences between the MCI MS and MCI XP groups during retrieval, especially within the right hippocampus. Thus, MS facilitated hippocampal functioning in a partially restorative manner. We conclude that cognitive rehabilitation techniques may help mitigate hippocampal dysfunction in MCI patients.

Objectives To evaluate the efficacy of mnemonic strategy training versus a matched-exposure control condition and also to examine the relationship between training-related gains, neuropsychological abilities, and medial temporal lobe volumetrics in patients with amnestic mild cognitive impairment (aMCI) and age-matched healthy controls. Methods Twenty-three of 45 screened healthy controls and 29 of 42 screened aMCI were randomized to mnemonic strategy or matched-exposure groups. Groups were run in parallel, with participants blind to the other intervention. All participants completed five sessions within two weeks. Memory testing for object-location associations was performed during sessions one and five and at a one-month follow-up. During sessions 2–4, participants received either mnemonic strategy training or a matched number of exposures with corrective feedback for a total of 45 object-location associations. Structural MRI was performed in most participants and medial temporal lobe volumetrics were acquired. Results Twenty-one healthy controls and 28 aMCI patients were included in data analysis. Mnemonic strategy training was significantly more beneficial than matched-exposure immediately after training, p =.006, pη2 = .16, and at one month, p<.001, pη2 = .35, regardless of diagnostic group (healthy controls or aMCI). Although aMCI patients demonstrated gains comparable to the healthy control groups, their overall performance generally remained reduced. Mnemonic strategy-related improvement was positively correlated with baseline memory and executive functioning and negatively with inferior lateral ventricle volume in aMCI patients; no significant relationships were evident in matched-exposure patients. Conclusions Mnemonic strategies effectively improve memory for specific content for at least one month in aMCI.