Increased sensitivity to proactive and retroactive interference in amnestic mild cognitive impairment: new insights

Background

Increased sensitivity to proactive (PI) and retroactive (RI) interference has been observed in amnestic mild cognitive impairment (aMCI). PI and RI are often explained as being the result of a response competition mechanism. However, patients with aMCI are supposed to suffer mostly from encoding deficits. We hypothesized that in aMCI interference may occur at encoding and not only at the retrieval stage.

Material and methods

We developed an original paradigm enabling PI and RI to be tested with and without response competitors. Eighteen young controls (YC), 16 elderly controls (EC) and 15 aMCI participated in the study.

Results

The YC and EC groups presented interference effects only in conditions that included a direct response competitor. In contrast, aMCI had interference effects in all conditions including the one without response competitor.

Conclusion

Increased sensitivity to interference in aMCI appears to occur at the encoding/consolidation stage and not only at the retrieval stage, as is the case in healthy subjects. This result is discussed in the context of the associative encoding deficits characterizing aMCI.     

Spatial navigation deficits in amnestic mild cognitive impairment with neuropsychiatric comorbidity

Aims: To find out whether neuropsychiatric comorbidity (comMCI) influences spatial navigation performance in amnestic mild cognitive impairment (aMCI).

Methods: We recruited aMCI patients with (n = 21) and without (n = 21) neuropsychiatric comorbidity or alcohol abuse, matched for global cognitive impairment and cognitively healthy elderly participants (HE, n = 22). They completed the Mini-Mental State Examination and a virtual Hidden Goal Task in egocentric, allocentric, and delayed recall subtests.

Results: In allocentric navigation, aMCI and comMCI performed significantly worse than HE and similarly to each other. Although aMCI performed significantly worse at egocentric navigation than HE, they performed significantly better than patients with comMCI.

Conclusions: Despite the growing burden of dementia and the prevalence of neuropsychiatric symptoms in the elderly population, comMCI remains under-studied. Since trials often assess “pure” aMCI, we may underestimate patients’ navigation and other deficits. This finding emphasizes the importance of taking account of the cognitive effects of psychiatric disorders in aMCI.     

Motor asymmetry and substantia nigra volume are related to spatial delayed response performance in Parkinson disease

Studies suggest motor deficit asymmetry may help predict the pattern of cognitive impairment in individuals with Parkinson disease (PD). We tested this hypothesis using a highly validated and sensitive spatial memory task, spatial delayed response (SDR), and clinical and neuroimaging measures of PD asymmetry. We predicted SDR performance would be more impaired by PD-related changes in the right side of the brain than in the left. PD (n = 35) and control (n = 28) participants performed the SDR task. PD participants either had worse motor deficits on the right (RPD) or left (LPD) side of the body. Some participants also had magnetic resonance imaging for measurement of their substantia nigra (SN) volumes. The LPD group performed worse on the SDR task than the RPD and control groups. Right SN volume accounted for a unique and significant portion of the variance in SDR error, with smaller volume predicting poorer performance. In conclusion, left motor dysfunction and smaller right SN volume are associated with poorer spatial memory.     

The update of semantic memories in amnestic mild cognitive impairment

It is still controversial to what extent neocortical consolidated memories are susceptible of change by processes of reconsolidation and transformation throughout experience, and whether the medial temporal lobes are necessary for this update of semantic consolidated memories, as they are for episodic remembering. We hypothesize that patients with amnestic mild cognitive impairment (aMCI) who have deficits in episodic memory may also have difficulties in updating information on added new features of objects. Sixteen participants with aMCI and 20 healthy control participants performed a semantic word-to-picture task, in which they were asked to identify as belonging to a given semantic category NEW objects, that have incorporated novel features, as well as OLD items, semantically and visually SIMILAR items and UNRELATED items. Patients with aMCI made a greater percentage of errors than healthy controls. Participants globally made greater percentages of errors in difficult types of items, namely NEW and SIMILAR, as compared to easier ones, OLD and UNRELATED. Importantly, an item by diagnostic group interaction effect was observed, and post hoc analysis showed that patients with aMCI made a higher percentage of errors than controls in NEW items only. In conclusion, patients with aMCI had a particular difficulty in identifying the NEW items of the word-to-picture task as compared to the control participants, supporting the concept of a flexible and dynamic conceptual knowledge system, involving the update of semantic memories and the integration of new attributes in a constant transformation process, which is impaired in these patients.     

Noise on, voicing off: Speech perception deficits in children with specific language impairment

Speech perception of four phonetic categories (voicing, place, manner, and nasality) was investigated in children with specific language impairment (SLI) (n = 20) and age-matched controls (n = 19) in quiet and various noise conditions using an AXB two-alternative forced-choice paradigm. Children with SLI exhibited robust speech perception deficits in silence, stationary noise, and amplitude-modulated noise. Comparable deficits were obtained for fast, intermediate, and slow modulation rates, and this speaks against the various temporal processing accounts of SLI. Children with SLI exhibited normal “masking release” effects (i.e., better performance in fluctuating noise than in stationary noise), again suggesting relatively spared spectral and temporal auditory resolution. In terms of phonetic categories, voicing was more affected than place, manner, or nasality. The specific nature of this voicing deficit is hard to explain with general processing impairments in attention or memory. Finally, speech perception in noise correlated with an oral language component but not with either a memory or IQ component, and it accounted for unique variance beyond IQ and low-level auditory perception. In sum, poor speech perception seems to be one of the primary deficits in children with SLI that might explain poor phonological development, impaired word production, and poor word comprehension.     

The free and cued selective reminding test for predicting progression to Alzheimer's disease in patients with mild cognitive impairment: A prospective longitudinal study

Amnestic mild cognitive impairment (aMCI) patients carry a greater risk of conversion to Alzheimer's disease (AD). Therefore, the International Working Group (IWG) on AD aims to consider some cases of aMCI as symptomatic prodromal AD. The core diagnostic marker of AD is a significant and progressive memory deficit, and the Free and Cued Selective Reminding Test (FCSRT) was recommended by the IWG to test memory in cases of possible prodromal AD. This study aims to investigate whether the performance on the FCSRT would enhance the ability to predict conversion to AD in an aMCI group. A longitudinal study was conducted on 88 aMCI patients, and neuropsychological tests were analysed on the relative risk of conversion to AD. During follow‐up (23.82 months), 33% of the aMCI population converted to AD. An impaired FCSRT TR was significantly associated with the risk of conversion to dementia, with a mean time to conversion of 25 months. The FCSRT demonstrates utility for detecting AD at its prodromal stage, thus supporting its use as a valid clinical marker.     

Memory for emotional faces in naturally occurring dysphoria and induced sadness

The aim was to establish if the memory bias for sad faces, reported in clinically depressed patients (Gilboa-Schechtman, Erhard Weiss, & Jeczemien, 2002; Ridout, Astell, Reid, Glen, & O'Carroll, 2003) generalises to sub-clinical depression (dysphoria) and experimentally induced sadness. Study 1: dysphoric (n = 24) and non-dysphoric (n = 20) participants were presented with facial stimuli, asked to identify the emotion portrayed and then given a recognition memory test for these faces. At encoding, dysphoric participants (DP) exhibited impaired identification of sadness and neutral affect relative to the non-dysphoric group (ND). At memory testing, DP exhibited superior memory for sad faces relative to happy and neutral. They also exhibited enhanced memory for sad faces and impaired memory for happy relative to the ND. Study 2: non-depressed participants underwent a positive (n = 24) or negative (n = 24) mood induction (MI) and were assessed on the same tests as Study 1. At encoding, negative MI participants showed superior identification of sadness, relative to neutral affect and compared to the positive MI group. At memory testing, the negative MI group exhibited enhanced memory for the sad faces relative to happy or neutral and compared to the positive MI group. Conclusion: MCM bias for sad faces generalises from clinical depression to these sub-clinical affective states.     

The free and cued selective reminding test: Validation for mild cognitive impairment and Alzheimer's disease

The International Working Group on Alzheimer's disease (AD) suggested the free and cued selective reminding test (FCSRT) to assess memory, as it showed high sensitivity and specificity in the differentiation of AD from healthy controls and other dementias. The FCSRT involves the use of selective reminding with semantic cueing in memory assessment. This study aims to validate the FCSRT for mild cognitive impairment (MCI) and AD through the analysis of the diagnostic accuracy and the suggestion of cut‐off scores. Patients were classified into two groups according to standard criteria: MCI (n = 100) and AD (n = 70). A matched control group (n = 101) of cognitively healthy subjects was included. The reliability and the validity of the FCSRT were analysed on the immediate (IR) and delayed (DR) recalls. The Cronbach's alpha was 0.915 for the IR and 0.879 for the DR. The total recall measures revealed good areas under the curve for MCI (IR: .818; DR: .828) and excellent for AD (IR: .987; DR: .991). Furthermore, the MCI group was subdivided with respect to a non‐similar/similar AD pattern of impairment, with almost half of the subjects showing an AD‐like decline. This analysis represents a novel contribution regarding the properties of the FCSRT in illustrating the heterogeneity of MCI at baseline. The FCSRT has proved to be a very useful tool in the characterization of the memory impairment of the AD spectrum.     

Effectiveness of follow‐up reminiscence therapy on autobiographical memory in pathological ageing

The objective is to examine the effects of reminiscence therapy (RT) on total, episodic and semantic autobiographical memory in amnestic mild cognitive impairment (aMCI) and Alzheimer's disease (AD) groups, testing the effects of RT on different stages of autobiographical memory, and its effectiveness at follow‐up. A sample composed of 43 aMCI (27 treatments, 16 controls) and 30 AD (15 treatments, 15 controls) subjects were evaluated with the Autobiographical Memory Interview (AMI) test. The RT consisted of 10 sessions lasting 60 minutes each. Both groups, aMCI and AD, showed significant effects on overall autobiographical memory; aMCI showed significant main effects on episodic and semantic autobiographical memory in the treatment group, increasing scores in both cases. For AD, significant effects were observed on autobiographical episodic memory, showing an increase in the treatment group from Time 1 to follow‐up; semantic memory showed a decrease in the control group from Time 1 to follow‐up. Results show that RT implementation and follow‐up are effective in increasing autobiographical memory in subjects with aMCI and AD.     

Visual associations cued recall A Paradigm for Measuring Episodic Memory Decline in Alzheimer’s Disease

Repeated measurements of episodic memory are needed for monitoring amnestic mild cognitive impairment (aMCI) and mild Alzheimer’s disease (AD). Most episodic memory tests may pose a challenge to patients, even when they are in the milder stages of the disease. This cross-sectional study compared floor effects of the Visual Association Test (VAT) and the Rey Auditory Verbal Learning Test (RAVLT) in healthy elderly controls and in patients with aMCI or AD (N = 125). A hierarchical multiple regression analysis was used to examine whether linear or quadratic trends best fitted the data of cognitive test performance across global cognitive impairment. Results showed that VAT total scores decreased linearly across the range of global cognitive impairment, whereas RAVLT total scores showed a quadratic trend, with total scores levelling off for 90% of aMCI patients and 94% of AD patients. We conclude that the VAT shows few if any floor effects in patients with aMCI and mild AD and is therefore a potentially promising cognitive test for monitoring episodic memory impairment.     

Alterations in working memory networks in amnestic mild cognitive impairment

Patients with amnestic mild cognitive impairment (aMCI) show preserved or mildly impaired working memory, despite their deficits in episodic memory. We aimed to identify performance and/or neural differences between aMCI patients and matched controls on a standard working memory fMRI task. Neuropsychological assessment demonstrated aMCI impairments in verbal and visual episodic long-term memory, with intact IQ and executive function. Participants completed a standard three-level N-back task where patients were unimpaired. Functional activations in the control group were found in expected areas, including the inferior parietal lobule and dorsolateral prefrontal cortex. Group differences were found in the insula and lingual gyrus and, in a region of interest analysis, in the hippocampus. In all cases, these were caused by an absence of task-related deactivations in the aMCI group. The results are consistent with reports of failure in task-related deacivations in aMCI and could be early indications of pathology.     

Lexical and semantic fluency discrepancy scores in aMCI and early Alzheimer's disease

Episodic memory is compromised in amnestic mild cognitive impairment (aMCI), but lesser deficits in other cognitive domains are also commonly observed and may be helpful in identifying this group. The relative difference in performance on lexical and semantic fluency tasks may be a sensitive and specific measure in aMCI and early Alzheimer's disease (AD). We compared four groups of participants, 35 early AD, 47 aMCI, 24 healthy controls, and 18 depressive out‐patient controls, on semantic and lexical fluency as well as other neuropsychological tests. Early AD and aMCI patients showed a distinct pattern of semantic impairment in the two fluency measures compared with the healthy and depressive controls. The findings implicate early failure of the semantic memory system in aMCI and AD and suggest that consideration of the discrepancy in performance on semantic and lexical fluency measures may help in the early identification of AD.     

Heart rate variability and drawing impairment in hypoxemic COPD

We studied 54 patients with hypoxemic chronic obstructive pulmonary disease (COPD). The Mini Mental State Examination and the Mental Deterioration Battery were used for neuropsychological assessment. Heart rate variability (HRV) was assessed based on 24-h Holter ECG recording. Mann–Whitney test was used to compare HRV parameters of patients performing normally or abnormally on individual neuropsychological tasks. Spearman’s rho was used to investigate the correlations between HRV parameters and neuropsychological scores, indexes of health status or COPD severity. Patients with defective performance at copying drawings with landmarks (CDL) test (N = 23) had lower very low frequency (VLF) power with respect to patients with normal performance (N = 31) (24 h: median 213; interquartile range 120–282 vs. 309; 188–431 ms², p = 0.043; daytime: 202; 111–292 vs. 342; 194–397 ms², p = 0.039). The CDL score correlated with the VLF power (24 h: ρ = 0.27, p = 0.049; daytime: ρ = 0.30, p = 0.028), and the normalized low frequency/high frequency (LF/HF) ratio (24 h: ρ = 0.27, p = 0.05; daytime: ρ = 0.33, p = 0.015). Sympathetic modulation decreased for increasing severity of COPD. In conclusion, drawing impairment correlates with depressed sympathetic modulation in patients with COPD, and both might be indexes of COPD severity.     

Part-set cueing impairment & facilitation in semantic memory

The present study explored the influence of part-set cues in semantic memory using tests of “free” recall, reconstruction of order, and serial recall. Nine distinct categories of information were used (e.g., Zodiac signs, Harry Potter books, Star Wars films, planets). The results showed part-set cueing impairment for all three “free” recall sets, whereas part-set cueing facilitation was evident for five of the six ordered sets. Generally, the present results parallel those often observed across episodic tasks, which could indicate that similar mechanisms contribute to part-set cueing effects in both episodic and semantic memory. A novel anchoring explanation of part-set cueing facilitation in order and spatial tasks is provided.     

Gesturing helps memory encoding in aMCI

Encoding in episodic memory is a step often impaired in patients with amnestic Mild Cognitive Impairment (aMCI). However, procedural memory processes are still relatively preserved. In line with previous research on the enactment effect, we investigated the potential benefit of encoding words combined with imitative gestures on episodic memory. Based on the Grober and Buschke’s free/cued recall procedure, we developed the Symbiosis test in which 13 patients with aMCI and 16 healthy elderly participants learned 32 words belonging to 16 different semantic categories either in a verbal encoding (A) or a bimodal (B; verbal and motor imitation) condition, using a blocked ABBA/BAAB procedure. Overall, memory retrieval was better in healthy participants than in patients with aMCI, and better for cued retrieval in the bimodal encoding (gesture cues) than the verbal encoding (category cues) condition, but there was no interaction effect between group and encoding conditions. These results show that performing concomitant gestures can enhance cued episodic memory retrieval in patients with aMCI and in healthy elderly controls. The Symbiosis test broadens the scope of the enactment effect, from action phrases to isolated words learning in patients with aMCI. Future work should investigate how bimodal encoding provides novel perspectives for memory rehabilitation in patients with aMCI.     

The effects of thought suppression on autobiographical memory recall

While it is well documented that autobiographical memory (ABM) recall is affected in Posttraumatic Stress Disorders (PTSD), less is known about the cognitive mechanisms that underlie this pattern. This paper presents two research studies which investigated the role of thought suppression in the recall of ABMs. Study 1 assessed the role of thought suppression as a correlate of ABM retrieval in an undergraduate student sample (n = 50). The results showed that higher levels of trait thought suppression were significantly correlated with faster recall of negative episodic memories as well as reduced recall of personal semantic memories. Thought suppression remained as a significant predictor of ABM recall, even when the participants' levels of depression and post-traumatic stress reactions were considered. Study 2 investigated the causal effects of thought suppression on ABM recall. 64 undergraduate students were shown a negative video clip and were asked either to suppress any thought of the video or simply to monitor their thoughts immediately thereafter. Results showed that suppression directly led to significantly enhanced negative episodic ABM recall, as well as a significantly reduced ability to recall personal semantic memories.     

Memory deficits for non-amnestic mild cognitive impairment

Non-amnestic mild cognitive impairment (naMCI) is one of the clinical subtypes of mild cognitive impairment (MCI). However, the characteristics of memory deficits in naMCI as assessed by clinical neuropsychological evaluations are not clear. In this study, a battery of neuropsychological tests was administered to 122 cognitively normal controls (NC), 133 amnestic mild cognitive impairment (aMCI) patients, and 72 naMCI patients. The results showed that in individuals with naMCI, episodic memory, and other cognitive domains were impaired. The Prospective Memory Test (PMT) event-based prospective memory (EBPM), the Symbol Digit Modalities Test (SDMT) Accidental Memory, Stick test (ST) visuoconstructional memory, and ST Working Memory were impaired, yet did not reach the level of aMCI. Semantic memory was affected to a degree comparable with aMCI. Some functions like Auditory Verbal Learning Test (AVLT) recognition, and Judgment of Confidence (JOC) were maintained, as well as PMT Time-Based Prospective Memory (TBPM). This study verified that memory impairment among individuals with naMCI was mainly in memory functions mediated by the frontotemporal cortex.     

The assessment of recognition memory using the Remember/Know procedure in amnestic mild cognitive impairment and probable Alzheimer’s disease

This study used the Remember/Know (R/K) procedure combined with signal detection analyses to assess recognition memory in 20 elders with amnestic mild cognitive impairment (aMCI), 10 patients with probable Alzheimer’s disease (AD) as well as matched healthy older adults. Signal detection analyses first indicated that aMCI and control participants were comparable on general recognition performance. As regards AD patients, they were impaired relative to both aMCI and healthy elders. When assessing Remember and Know responses the aMCI group showed diminished sensitivity for Remember responses but intact Know responses compared to healthy elders. In contrast, AD patients showed decreased sensitivity for both Remember and Know responses compared to control and aMCI participants. The response bias index revealed that AD patients were more liberal than aMCI and control participants when providing Know responses. On the other measures, response bias was comparable between the groups. Overall, this study indicates that the R/K procedure can characterize different aspects of recognition memory performance in persons with aMCI or AD.     

Type-specific proactive interference in patients with semantic and phonological STM deficits

Prior neuropsychological evidence suggests that semantic and phonological components of short-term memory (STM) are functionally and neurologically distinct. The current paper examines proactive interference (PI) from semantic and phonological information in two STM-impaired patients, DS (semantic STM deficit) and AK (phonological STM deficit). In Experiment 1 probe recognition tasks with open and closed sets of stimuli were used. Phonological PI was assessed using nonword items, and semantic and phonological PI was assessed using words. In Experiment 2 phonological and semantic PI was elicited by an item recognition probe test with stimuli that bore phonological and semantic relations to the probes. The data suggested heightened phonological PI for the semantic STM patient, and exaggerated effects of semantic PI in the phonological STM case. The findings are consistent with an account of extremely rapid decay of activated type-specific representations in cases of severely impaired phonological and semantic STM.     

Functional imaging of working memory and peripheral endothelial function in middle-aged adults

The current study examined the relationship between a prognostic indicator of vascular health, flow-mediated dilation (FMD), and working memory-related brain activation in healthy middle-aged adults. Forty-two participants underwent functional magnetic resonance imaging while completing a 2-Back working memory task. Brachial artery endothelial-dependent flow-mediated dilation (FMD) was assessed using B-mode ultrasound. The relationship between FMD and task-related brain activation in a priori regions of interest was modeled using hierarchical linear regression. Brachial FMD, was significantly related to reduced working memory-related activation in the right superior parietal lobule (β = 0.338, p = 0.027), independent of age, sex, systolic blood pressure, and full scale IQ (F(5, 36) = 2.66, p = 0.038). These data provide preliminary support for the association between a preclinical marker of endothelial dysfunction and cerebral hemodynamic alterations in healthy middle-aged adults. Considering the modifiable nature of endothelial function, additional investigations on the prognostic significance of FMD on future cognitive impairment are warranted.