Memory In Mild Cognitive Impairment Research Articles

Bodily and Visual-Cognitive Navigation Aids to Enhance Spatial Recall in Mild Cognitive Impairment.

Individuals with mild cognitive impairment (MCI) syndrome often report navigation difficulties, accompanied by impairments in egocentric and allocentric spatial memory. However, studies have shown that both bodily (e.g., motor commands, proprioception, vestibular information) and visual-cognitive (e.g., maps, directional arrows, attentional markers) cues can support spatial memory in MCI. We aimed to assess navigation cues for innovative spatial training in aging. Fifteen MCI patients were recruited for this study. Their egocentric and allocentric memory recall performances were tested through a navigation task with five different virtual reality (VR) assistive encoding navigation procedures (bodily, vision only, interactive allocentric map, reduced executive load, free navigation without cues). Bodily condition consisted of an immersive VR setup to engage self-motion cues, vision only condition consisted of passive navigation without interaction, in the interactive allocentric map condition patients could use a bird-view map, in the reduced executive load condition directional cues and attentional markers were employed, and during free navigation no aid was implemented. Bodily condition improved spatial memory compared to vision only and free navigation without cues. In addition, the interactive allocentric map was superior to the free navigation without cues. Surprisingly, the reduced executive load was comparable to vison only condition. Moreover, a detrimental impact of free navigation was observed on allocentric memory across testing trials. These findings challenge the notion of an amodal representation of space in aging, suggesting that spatial maps can be influenced by the modality in which the environment was originally encoded.

Improvement in Motor Skills, Attention, and Working Memory in Mild Cognitive Impairment and Alzheimer’s Disease Patients Using COSMA Cognitive App

Improvement in Motor Skills, Attention, and Working Memory in Mild Cognitive Impairment and Alzheimer’s Disease Patients Using COSMA Cognitive App

Neuromodulation for Mild Cognitive Impairment: Improvements in Spatial Navigation and Associative Memory with Acute Transcutaneous Vagus Nerve Stimulation: VINCI‐AD

AbstractBackgroundNew therapeutic strategies to treat Mild Cognitive Impairment (MCI) are urgently needed. Transcutaneous Vagus Nerve Stimulation (tVNS) is a neuromodulation technique which uses a handheld device to peripherally stimulate the afferent vagus nerve. tVNS has shown promise in augmenting memory in cognitively healthy populations but data in cognitively impaired populations is sparse.MethodVINCI‐AD is an investigator‐led, single‐blind, sham‐controlled crossover pilot study assessing the effects of tVNS in amnestic MCI. All participants have MCI (CDR global 0.5) with amnestic neuropsychological profile (RBANS delayed memory index <85). Participants are randomised over 3 study visits to baseline (no stimulation) active stimulation (at the CC of left ear) or sham stimulation (earlobe). Cognitive tests include Face‐Name Association Task (FNAT), Sustained Attention Response Test (SART) and Sea Hero Quest Navigation Test (SHQ) among others.ResultInterim data analysis of 28 participants is presented (mean age 71.5 (range 55‐85), 17 male, RBANS DMI 73.3 ±11.1). CSF AD biomarkers were positive for 75% (21/28) (AB‐42 460.4pg/ml (± 83.3pg/ml) and p‐tau181 82.5pg/ml [± 53.2pg/ml]) and 78% (22/28) of participants had a Charleston Comorbidity Index of ≥3. Mean tVNS stimulation time pre‐cognitive assessments was 21.2 minutes, with mean amplitude setting during active stimulation of 2.5mA (1.8‐4.5) and sham of 2.0mA (0.9‐3.1). During FNAT, active tVNS had no effect on facial recognition or reaction times, however recall accuracy was significantly improved (69.2% ±3.13) compared to baseline (44.7% ±3.51 p = 0.016) and sham (50.1% ±3.28 p = 0.021) and during active tVNS spatial navigation (38.94sec [±1.68]) was quicker than baseline (51.49sec (±3.2) p = 0.0164) and sham (51.9sec (±3.15) p = 0 .0038). We noted no significant improvements in SART or other cognitive tests performance during tVNS.ConclusiontVNS may be a useful complementary tool to augment spatial and associative memory in MCI. Further larger studies are needed to delineate precise settings in this population.

Circulating cell‐free mitochondrial DNA (ccf‐mtDNA) and memory in mild cognitive impairment (MCI) and Alzheimer’s disease (AD)

AbstractBackgroundCirculating cell‐free mitochondrial DNA (ccf‐mtDNA), a measure of mitochondrial dysfunction, is emerging as a potential biomarker for early Alzheimer’s disease (AD). Decreased levels of cerebrospinal fluid ccf‐mtDNA concentrations have been detected in early AD patients. Few studies have investigated peripheral ccf‐mtDNA in early AD or with cognitive measures, much less evaluating the role of physical activity within the relationships. Considering the hallmark of episodic memory impairment in early AD, we examined the association between serum ccf‐mtDNA and memory, while considering potential contributing factors, physical activity level and age.MethodsParticipants were diagnosed with mild cognitive impairment (MCI) or mild AD using the Diagnostic and Statistical Manual of Mental Disorders criteria for mild or major neurocognitive disorder. Serum ccf‐mtDNA concentration (copies/uL) was measured using quantitative polymerase chain reaction from circulating cell free DNA purified by spin columns with primer for the MT‐ND4 gene. Memory was assessed using the Word Recall Task from the Alzheimer’s Disease Assessment Scale‐Cog (ADAS‐Cog). Physical activity level was assessed by Leisure‐Time Exercise Questionnaire (LTEQ). Linear regression analyses were used to assess the association between ccf‐mtDNA levels and recall memory with a priori covariates, age and LTEQ score. Ccf‐mtDNA levels were log‐transformed prior to analyses due to significant departure from normality in Shapiro‐Wilk tests.ResultsOf 29 participants [17 (59%) male, 21 (72%) MCI], the mean (SD) age was 74.2 (8.7), years of education was 16.2 (2.2), Montreal Cognitive Assessment (MoCA) total score was 22.1 (3.3), LTEQ score was 36.2 (17.4), and ccf‐mtDNA levels were 2545.8 (2223.6) copies/uL. Higher ccf‐mtDNA was associated with worse recall [F(3,25) = 5.21, R2 = .39, p = .006]. Controlling for LTEQ and age, one log ccf‐mtDNA unit was associated with 1.87 (SE = .71) fewer words recalled (p = .01, f2 = .21).ConclusionIn this sample, higher serum ccf‐mtDNA concentrations were associated with worse recall, controlling for age and physical activity level. This relationship supports the potential involvement of mitochondrial dysfunction in cognitive functions and neurodegenerative diseases and suggest the need for further research to explore the role of physical activity and age with mitochondrial dysfunction and memory.

Time-Based and Event-Based Prospective Memory in Mild Cognitive Impairment and Alzheimer's Disease Patients: A Systematic Review and Meta-analysis.

Prospective memory (PM) is the ability to remember to perform planned actions in a future moment and it is of fundamental importance for an independent and autonomous lifestyle from development to late adulthood. Deficits in episodic memory and executive functions, which are involved in PM are characteristic features of mild cognitive impairment (MCI) and Alzheimer's disease (AD). Considering that the number of older adults is drastically increasing over the next decades, it is of great interest to understand how PM decline in healthy older adults and patients with different degree of cognitive decline. The present meta-analysis included 46 studies investigating PM performance in AD patients (17 studies) and people with MCI (24 studies); 5 studies included both clinical conditions in the same article. The 46 studies contributed a total of 63 independent samples and 129 effect sizes from 4668 participants (2115 patients and 2553 controls). Unlike previous reviews of the literature, our results with a larger and updated sample of studies confirmed lower PM abilities in AD compared to MCI and controls, although we did not observe conclusive differences between event-based and time-based PM in patients. Surprisingly, PM deficits shown by MCI and AD patients have decreased across years, in parallel to a reduction of the evidence of publication bias and an increase in the number of observations per task. We propose the use of more reliable research designs as one plausible explanation for the reduction of PM impairments.

Olfactory memory in mild cognitive impairment and Alzheimer's disease.

Olfaction is impaired in Alzheimer's disease (AD). However, olfactory memory has rarely been examined. As the pathogenesis of AD remains largely unknown, collecting more data regarding the occurrence and progression of its symptoms would help gain more insight into the disease. To investigate olfactory memory and its relationship with verbal memory and other clinical features in patients with early-stage AD. Three groups of participants were enrolled in this study: patients with mild dementia due to AD (MD-AD, N = 30), patients with mild cognitive impairment due to AD (MCI-AD, N = 30), and cognitively normal older participants (CN, N = 30). All participants underwent cognitive evaluation (Clinical Dementia Rating scale, Mini Mental State Examination, Alzheimer's Disease Assessment Scale-Cognitive Subscale, delayed verbal recall, and verbal fluency tests) and assessment of olfactory immediate and delayed recognition memory. Olfactory immediate and delayed recognition memory scores were significantly lower in the MD-AD group than in the MCI-AD and CN groups. The MCI-AD and CN groups did not differ significantly [in both cases, Kruskal-Wallis test, p < 0.05; post hoc analysis revealed significant differences between the MD-AD and MCI-AD groups and between the MD-AD and CN groups (p < 0.05), and no significant difference between the MCI-AD and CN groups (p > 0.05)]. Verbal immediate recall, delayed recall after 5 min, and delayed recall after 30 min scores were significantly worse in the MD-AD and MCI-AD groups than in the CN group. MD-AD and MCI-AD groups did not differ significantly [in all cases Kruskal-Wallis test, p < 0.05; post hoc analysis revealed significant differences between MD-AD and CN groups, and MCI-AD and CN groups (p < 0.05) and no significant difference between MD-AD and MCI-AD groups (p > 0.05)]. Duration of AD symptoms was a strong predictor of both immediate and delayed olfactory recognition memory scores. Olfactory memory impairment was observed in patients with AD. The changes progress during the course of the disease. However, unlike verbal memory, olfactory memory is not significantly impaired in the prodromal stage of AD.

Subjective and objective prospective memory in mild cognitive impairment and Alzheimer’s disease

AbstractBackgroundProspective memory (PM) involves remembering to execute an intended action in the future, and it is an important skill that predicts everyday functioning in older adults. Older adults with mild cognitive impairment (MCI) and Alzheimer’s disease (AD) exhibit difficulties in PM. This study examined subject and caregiver reports of PM ability and their associations with objective PM.MethodParticipants included older healthy controls (n = 58), persons with MCI (n = 65), and individuals with AD (n = 18). The Prospective‐Retrospective Memory Questionnaire was used to assess self‐ and caregiver‐reports of participants’ PM skills. Objective abilities were measured using tests of “simple” and “complex” PM. Simple PM was defined as remembering to perform a single action in the future. Complex PM was defined as selecting the correct action based on the context.ResultRegression analyses revealed that caregiver‐reported PM predicted complex PM only in healthy controls. In contrast, self‐reported PM did not predict objective PM in any group.ConclusionThe results showed that self‐reports of PM are not good indicators of objective PM. While caregiver reports may be more accurate in relation to PM in healthy older adults, they do not align as well with objective PM for those with cognitive impairment. Overall, this research indicates that objective measures should be used to evaluate this important skill that contributes to everyday functioning.

Background Music and Memory in Mild Cognitive Impairment: The Role of Interindividual Differences.

Recent research has shown that background music may improve memory consolidation and retrieval. Nevertheless, in the clinical conditions preceding dementia such as mild cognitive impairment (MCI), there is no current evidence speaking to what effect background music during memory tasks has on impaired cognition. Across three experiments, we investigated if background music is able to improve memory performance, the most impacted cognitive domain in amnestic MCI. We tested the effect of background music by using a face recognition memory task in patients with amnestic MCI. In Experiment 1, we tested the effect of background music on memory when it was played solely during an encoding phase. In Experiment 2, we explored effects of background music when played during both encoding and recognition phases. In Experiment 3, we explored the role of musically induced arousal on memory. The main finding from these three experiments was that background music played during a memory task did not improve or worsen participant performance. However, when exposed to high-arousal music, memory performance was predicted by individual mood regulation. For low-arousal music conditions, there was a negative relationship between rating scores for music pleasantness and performance on the memory task. Our results suggest that the benefits of background music on memory in individuals with MCI are modulated by interindividual preferences towards music.

Forgetting Rates of Prose Memory in Mild Cognitive Impairment.

Some authors report steeper slopes of forgetting in early Alzheimer's disease (AD), while others do not. Contrasting findings are thought to be due to methodological inconsistencies or variety of testing methods, yet they also emerge when people are assessed on the same testing procedure. We aimed to assess if forgetting slopes of people with mild cognitive impairment due to AD (MCI-AD) are different from age-matched healthy controls (HC) by using a prose paradigm. Twenty-nine people with MCI-AD and twenty-six HC listened to a short prose passage and were asked to freely recall it after delays of 1 h and 24 h. Generalized linear mixed modelling revealed that, compared to HC, people with MCI-AD showed poorer encoding at immediate recall and steeper forgetting up to 1 h in prose memory as assessed by free recall and with repeated testing of the same material. Forgetting rates between groups did not differ from 1 h to 24 h. The differences observed in MCI-AD could be due to a post-encoding deficit. These findings could be accounted either by a differential benefit from retrieval practice, whereby people with MCI-AD benefit less than HC, or by a working memory deficit in people with MCI-AD, which fails to support their memory performance from immediate recall to 1 h.

Time Perception and Memory in Mild Cognitive Impairment and Alzheimer's Disease: A Preliminary Study.

Episodic memory is a system that receives and stores information about temporally dated episodes and their interrelations. Our study aimed to investigate the relevance of episodic memory to time perception, with a specific focus on simultaneity/order judgment. Experiment 1 employed the simultaneity judgment task to discern differences in time perception between patients with mild cognitive impairment or dementia, and age-matched normals. A mathematical analysis capable of estimating subjects' time processing was utilized to identify the sensory and decisional components of temporal order and simultaneity judgment. Experiment 2 examined how differences in temporal perception relate to performance in temporal order memory, in which time delays play a critical role. The temporal decision windows for both temporal order and simultaneity judgments exhibited marginal differences between patients with episodic memory impairment, and their healthy counterparts (p = 0.15, t(22) = 1.34). These temporal decision windows may be linked to the temporal separation of events in episodic memory (Pearson's ρ = -0.53, p = 0.05). Based on our findings, the frequency of visual events accumulated and encoded in the working memory system in the patients' and normal group appears to be approximately (5.7 and 11.2) Hz, respectively. According to the internal clock model, a lower frequency of event pulses tends to result in underestimation of event duration, which phenomenon might be linked to the observed time distortions in patients with dementia.

Regional amyloid correlates of cognitive performance in ageing and mild cognitive impairment.

Beta-amyloid deposition is one of the earliest pathological markers associated with Alzheimer's disease. Mild cognitive impairment in the setting of beta-amyloid deposition is considered to represent a preclinical manifestation of Alzheimer's disease. In vivo imaging studies are unique in their potential to advance our understanding of the role of beta-amyloid deposition in cognitive deficits in Alzheimer's disease and in mild cognitive impairment. Previous work has shown an association between global cortical measures of beta-amyloid deposition (‘amyloid positivity’) in mild cognitive impairment with greater cognitive deficits and greater risk of progression to Alzheimer's disease. The focus of the present study was to examine the relationship between the regional distribution of beta-amyloid deposition and specific cognitive deficits in people with mild cognitive impairment and cognitively normal elderly individuals. Forty-seven participants with multi-domain, amnestic mild cognitive impairment (43% female, aged 57–82 years) and 37 healthy, cognitively normal comparison subjects (42% female, aged 55–82 years) underwent clinical and neuropsychological assessments and high-resolution positron emission tomography with the radiotracer 11C-labelled Pittsburgh compound B to measure beta-amyloid deposition. Brain–behaviour partial least-squares analysis was conducted to identify spatial patterns of beta-amyloid deposition that correlated with the performance on neuropsychological assessments. Partial least-squares analysis identified a single significant (P < 0.001) latent variable which accounted for 80% of the covariance between demographic and cognitive measures and beta-amyloid deposition. Performance in immediate verbal recall (R = −0.46 ± 0.07, P < 0.001), delayed verbal recall (R = −0.39 ± 0.09, P < 0.001), immediate visual-spatial recall (R = −0.39 ± 0.08, P < 0.001), delayed visual-spatial recall (R = −0.45 ± 0.08, P < 0.001) and semantic fluency (R = −0.33 ± 0.11, P = 0.002) but not phonemic fluency (R = −0.05 ± 0.12, P < 0.705) negatively covaried with beta-amyloid deposition in the identified regions. Partial least-squares analysis of the same cognitive measures with grey matter volumes showed similar associations in overlapping brain regions. These findings suggest that the regional distribution of beta-amyloid deposition and grey matter volumetric decreases is associated with deficits in executive function and memory in mild cognitive impairment. Longitudinal analysis of these relationships may advance our understanding of the role of beta-amyloid deposition in relation to grey matter volumetric decreases in cognitive decline.

Effects of vitamin B12 on cognitive function in elderly patients

AbstractBackgroundEstablishing preventive and therapeutic methods for Alzheimer's disease (AD) is an urgent issue. Because Vitamin B12(VB12) has a neuroprotective effect on the central nervous system, it has begun to receive attention. Recently, we found that VB12 can suppress β‐amyloid toxicity in vitro. Besides, it has been reported that VB12 might be useful for keeping memory in Mild Cognitive Impairment (MCI). To clarify the effects of VB12 in AD and MCI patients, we examined the effects of the VB12 on cognitive function and regional cerebral blood flow (rCBF).MethodWe examined 46 participants who consulted to our memory clinic. They were divided into three groups: Alzheimer's disease (AD), mild cognitive impairment (MCI), and healthy controls (HC) based on the National Institute on Aging‐Alzheimer’s Association (NIA‐AA) diagnostic criteria. We used Wechsler Memory Scale‐Revised(WMS‐R) to assess the cognitive function and evaluate what kind of function is degraded. Three‐dimensional stereotactic surface projection(3D‐SSP)was used to quantify the rCBF of hippocampus, thalamus, and callosomarginal regions, which had a well‐established connection with AD. Multiple regression analysis was conducted to examine the correlations among serum VB12, WMS‐R, and rCBF in each group.ResultRegarding the correlations between VB12 and memory function, we found that the VB12 was significantly correlated with the WMS‐R scores of visual paired association I/II in the MCI group and the verbal paired associates I in the AD group (all, p&lt;0.05). Besides, there were significant correlations between VB12 and WMS‐R scores of the visual reproduction I, logical memory I, and visual memory span in the HC group (all, p&lt;0.05). Regarding the correlations between VB12 and rCBF, VB12 concentration was significantly correlated with the rCBF of the left hippocampal in the MCI group (all, p&lt;0.05). Neither AD nor HC groups showed significant correlations between rCBF and VB12. Finally, the rCBF of the left hippocampus was positively correlated with visual paired association I/II(all, p&lt;0.05).ConclusionThese results suggested that VB12 affects memory function and rCBF, especially in the MCI. Considering the relationship between WMS‐R and rCBF, VB12 may affect the progression of dementia. The early intervention with VB12 can be more effective in AD treatment strategies.

Evaluating the relationship between vascular endothelial growth factor (VEGF) and cognitive improvements following exercised‐primed transcranial direct current stimulation (tDCS) in mild cognitive impairment (MCI) and Alzheimer’s disease (AD)

AbstractBackgroundVEGF has been associated with memory decline in neurodegenerative diseases. As an angiogenesis biomarker, VEGF should be analyzed to better understand the variable treatment response from tDCS, a non‐invasive brain stimulation, and the priming effect of exercise on tDCS for memory improvements in MCI and AD. Using blinded data from an ongoing clinical trial (EXPRESS), we aimed to evaluate the ability of serum VEGF to predict improvements for recall memory in MCI and mild AD patients.MethodParticipants were enrolled in a five‐week, randomized, blinded tDCS clinical trial to receive either exercise and sham tDCS, exercise and tDCS, or exercise‐education only and tDCS intervention. Exercise groups included a three‐week ramp‐up period. Participants were diagnosed using the Diagnostic and Statistical Manual of Mental Disorders (DSM‐5) criteria for major or mild neurocognitive disorder due to AD or mixed AD/vascular disease (etiology). VEGF serum concentrations were measured from blood samples at screening. Recall memory was assessed using the Word Recall Task from the Alzheimer's Disease Assessment Scale‐Cog (ADAS‐Cog) at screening, baseline and endpoint (2 weeks from baseline). Analysis of variance (ANOVA) evaluated recall memory and VEGF concentrations at screening between the two etiology groups. Multiple linear regression analysis determined the association between VEGF concentrations (pg/mL) and recall memory score improvements over treatment period (Δrecall).ResultIn 17 participants (58.8% male, 70.6% MCI, mean(±SD) age 72.8±7.2, years of education 17.1±2.0, VEGF 332.4±157.5, Δrecall 0.5±0.9), six participants (35.3%) were diagnosed as AD etiology only and eleven participants (64.7%) were mixed vascular/AD etiology with no differences in recall memory [F(1,15)=0.019,p=0.893] or VEGF concentrations [F(1,15)=1.488,p=0.241] between these two groups at screening. The regression analysis found that VEGF and etiology predicted Δrecall [F(2,14)=7.103,p=0.007,R2=0.504]. Controlling for etiology, VEGF concentrations were associated with Δrecall [B(SE)=‐0.003(0.001),p=0.039]; Δrecall decreased 0.003 for each pg/mL of VEGF.ConclusionIn this pilot sample, lower serum VEGF concentrations at screening predicted greater recall memory improvements when controlling for etiology. After un‐blinding, longitudinal analysis and a larger sample size will allow further examination of VEGF’s predictive and monitoring capacity as a biomarker for recall memory and other cognitive responses to exercise‐primed tDCS.

Emotion regulation in mild cognitive impairment and subjective cognitive decline

AbstractBackgroundOur previous research in emotional verbal memory in mild cognitive impairment (MCI) and work from others suggest the hypothesis that emotion dysregulation is a signature of Alzheimer’s disease (AD) risk. Whether subjective cognitive decline (SCD), conceptualized as a possible preclinical stage of AD, is associated with emotion dysregulation is unknown. In the current study, we compared responses on the Cognitive Emotion Regulation Questionnaire (CERQ) and behavioural responses on a threat task amongst SCD, MCI, and cognitively unimpaired (CU) older adults.MethodsThe sample included 146 older adults free of lifetime history of psychiatric illness/neurological conditions: 33 MCI [17F, age 72.3(SD7.6)] defined as subjective memory/other cognitive complaints, impaired neuropsychological (NP) test performance, and functional independence, 71 SCD [49F, age 71.1(SD6.3)] based on subjective memory decline with worry with normal NP performance, and 42 CU [27F, age 70.6(SD6.8)] based on absence of subjective memory decline and normal NP test scores. Participants completed the CERQ which assesses cognitive coping strategies in negative emotional situations. A subset (19 MCI, 43 SCD, 19 CU) completed a computerized task in which they rated a physical feature or threat level of faces with varying degrees of threat. Multivariate ANOVA was used to examine group differences, followed by Sidak‐adjusted post hoc comparisons.ResultsOn the CERQ, groups differed in use of catastrophizing [F(2, 142)=3.51, P=.032], with a trend for use of rumination (P=.07), attributable to greater use of both strategies in MCI compared to CU (P=.04). On the threat task, groups differed in response latencies to judging physical features of threatening faces relative to neutral [F(2, 78)=3.17, P=.048)]. Relative to CU, SCD participants were slower to make physical judgements of threatening faces compared to neutral (P=.026).ConclusionsOlder adults with SCD do not report greater use of maladaptive emotion regulation strategies compared to CU. However, alterations in behavioural responses to threat versus neutral in SCD may represent deficits in regulating attention towards negative emotional information, similar to mood‐congruent cognitive biases observed in depression. These preliminary data highlight the need to increase our understanding of explicit and implicit emotional processing in older adults at risk for AD.

Photobiomodulation Improves Memory in Mild Cognitive Impairment: Three Case Reports

Three patients (mean age = 62) received 18-sessions of PBM stimulation twice per week for nine weeks. Each patient was assessed with Rey- Osterrieth Complex Figure Test (Rey-O testing visual memory) and Hong Kong List Learning Test (HKLLT testing verbal memory), Clinical Dementia Rating Scale (CDR), Functional Activities Questionnaire (FAQ), Geriatric Anxiety Scale-10 Item Version (GAS-10) and Chinese Geriatric Depression Scale (CGDS) before and after PBM.

How can automated linguistic analysis help to discern functional cognitive disorder from healthy controls and mild cognitive impairment?

AimsThe disease burden of cognitive impairment is significant and increasing. The aetiology of cognitive impairment can be structural, such as in mild cognitive impairment (MCI) due to early Alzheimer's disease (AD), or in functional cognitive disorder (FCD), where there is no structural pathology. Many people with FCD receive a delayed diagnosis following invasive or costly investigations. Accurate, timely diagnosis improves outcomes across all patients with cognitive impairment. Research suggests that analysis of linguistic features of speech may provide a non-invasive diagnostic tool. This study aimed to investigate the linguistic differences in conversations between people with early signs of cognitive impairment with and without structural pathology, with a view to developing a screening tool using linguistic analysis of conversations.MethodIn this explorative, cross-sectional study, we recruited 25 people with MCI considered likely due to AD, (diagnosed according to Petersen's criteria and referred to as PwMCI), 25 healthy controls (HCs) and 15 people with FCD (PwFCD). Participants’ responses to a standard questionnaire asked by an interactional virtual agent (Digital Doctor) were quantified using previously identified parameters. This paper presents statistical analyses of the responses and a discussion of the results.ResultPwMCI produced fewer words than PwFCD and HCs. The ratio of pauses to speech was generally lower for PwMCI and PwFCD than for HCs. PwMCI showed a greater pause to speech ratio for recent questions (such as ‘what did you do at the weekend?’) compared with the HCs. Those with FCD showed the greatest pause to speech ratio in remote memory questions (such as ‘what was your first job?’). The average age of acquisition of answers for verbal fluency questions was lower in the MCI group than HCs.ConclusionThe results and qualitative observations support the relative preservation of remote memory compared to recent memory in MCI due to AD and decreased spontaneous elaboration in MCI compared with healthy controls and patients with FCD. Word count, age of acquisition and pause to speech ratio could form part of a diagnostic toolkit in identifying those with structural and functional causes of cognitive impairment. Further investigation is required using a large sample.

Egocentric and Allocentric Spatial Memory in Mild Cognitive Impairment with Real-World and Virtual Navigation Tasks: A Systematic Review.

Background:Spatial navigation is the ability to estimate one’s position on the basis of environmental and self-motion cues. Spatial memory is the cognitive substrate underlying navigation and relies on two different reference frames: egocentric and allocentric. These spatial frames are prone to decline with aging and impairment is even more pronounced in Alzheimer’s disease (AD) or in mild cognitive impairment (MCI).Objective:To conduct a systematic review of experimental studies investigating which MCI population and tasks are used to evaluate spatial memory and how allocentric and egocentric deficits are impaired in MCI after navigation.Methods:PRISMA and PICO guidelines were applied to carry out the systematic search. Down and Black checklist was used to assess methodological quality.Results:Our results showed that amnestic MCI and AD pathology are the most investigated typologies; both egocentric and allocentric memory are impaired in MCI individuals, and MCI due to AD biomarkers has specific encoding and retrieval impairments; secondly, spatial navigation is principally investigated with the hidden goal task (virtual and real-world version), and among studies involving virtual reality, the privileged setting consists of non-immersive technology; thirdly, despite subtle differences, real-world and virtual versions showed good overlap for the assessment of MCI spatial memory.Conclusion:Considering that MCI is a subclinical entity with potential risk for conversion to dementia, investigating spatial memory deficits with navigation tasks might be crucial to make accurate diagnosis and rehabilitation.

A Meta-Analysis of Semantic Memory in Mild Cognitive Impairment

Accumulating evidence over the past decade suggests that semantic deficits represent a consistent feature of Mild Cognitive Impairment (MCI). A meta-analysis was performed to examine if semantic deficits are consistently found in patients with MCI. Studies meeting all inclusion criteria were selected for the current meta-analysis. An effect size and a weight were calculated for each study. A random effect model was performed to assess the overall difference in semantic performances between MCI patients and healthy subjects. 22 studies (476 healthy participants, 476 MCI patients, mean Mini Mental Status Examination of the MCI patients: 27.05 ± 0.58) were included in the meta-analysis. Results indicate that MCI patients systematically performed significantly worse than healthy matched controls in terms of overall semantic performance (mean effect size of 1.02; 95% CI [0.80; 1.24]). Semantic deficits are a key feature of MCI. Semantic tests should be incorporated in routine clinical assessments.

Event-related potential and EEG oscillatory predictors of verbal memory in mild cognitive impairment.

Reliable biomarkers of memory decline are critical for the early detection of Alzheimer’s disease. Previous work has found three EEG measures, namely the event-related brain potential P600, suppression of oscillatory activity in the alpha frequency range (∼10 Hz) and cross-frequency coupling between low theta/high delta and alpha/beta activity, each of which correlates strongly with verbal learning and memory abilities in healthy elderly and patients with mild cognitive impairment or prodromal Alzheimer’s disease. In the present study, we address the question of whether event-related or oscillatory measures, or a combination thereof, best predict the decline of verbal memory in mild cognitive impairment and Alzheimer’s disease. Single-trial correlation analyses show that despite a similarity in their time courses and sensitivities to word repetition, the P600 and the alpha suppression components are minimally correlated with each other on a trial-by-trial basis (generally |rs| < 0.10). This suggests that they are unlikely to stem from the same neural mechanism. Furthermore, event-related brain potentials constructed from bandpass filtered (delta, theta, alpha, beta or gamma bands) single-trial data indicate that only delta band activity (1–4 Hz) is strongly correlated (r = 0.94, P < 0.001) with the canonical P600 repetition effect; event-related potentials in higher frequency bands are not. Importantly, stepwise multiple regression analyses reveal that the three event-related brain potential/oscillatory measures are complementary in predicting California Verbal Learning Test scores (overall R2’s in 0.45–0.63 range). The present study highlights the importance of combining EEG event-related potential and oscillatory measures to better characterize the multiple mechanisms of memory failure in individuals with mild cognitive impairment or prodromal Alzheimer’s disease.

Assessment of semantic memory in mild cognitive impairment: The psychometric properties of a novel semantic battery

Semantic memory is stable in healthy older adults but shows decline in mild cognitive impairment (MCI). Current measures of semantic function do not assess multiple aspects of semantic function and/or are time-consuming to administer. Here we report the psychometric properties of a battery to detect semantic impairment that we recently developed and published. Study 1 determined the face validity of the battery; interviews were conducted with five professionals with expertise in MCI and language. Face validity interviews suggested the battery appropriately assesses semantic impairments. Study 2 assessed convergent validity and reliability (inter-rater reliability, test-retest reliability, and internal consistency). Participants included 102 healthy older adults and 60 people with MCI who completed a four-task semantic battery. Results demonstrate that performance on the semantic battery correlates with traditional measures of semantic function, inter-rater reliability and internal consistency was high, and there was no significant change in mean scores between participants’ first and second testing sessions. The present findings suggest that the semantic battery is a reliable and valid assessment of semantic function. It is currently recommended for research use only.