Visual and verbal working memory and its relationship to subcortical regions in statistically-determined mild cognitive impairment

Background: Fuster (2008) observed that temporal organization modulate executive control mechanisms by generating (1) attention towards test parameters (working memory), (2) the capacity to execute a task (preparatory set), and (3) the ability to inhibit external/internal stimuli (inhibitory control). We investigated Fuster\u27s model (2008) using response latency on visual and verbal working memory tasks in patients with suspected mild cognitive impairment (MCI). Methods: An iPad-version of the Backward Digit Span Test (BDT) and Symbolic Working Memory Test (SWM) were used. Outcome variables were latency for each correct serial position and volumetric subcortical regions using NeuroQuant® software. Results: Mixed-model analyses found within-group differences on both BDT and SWM. Moreover, group by latency interaction for each position as a function of total time was observed on the BDT. Correlations between total time for correct trials and neuropsychological measures of processing speed and visuospatial operations were significant for the BDT. Finally, MRI was not associated with any serial order position. Conclusions: Consistent with Fuster\u27s model, BDT latencies illustrate a tripartite neurocognitive construct. The allocation of latency for correct trials differed between the MCI and non-MCI groups to suggest distinct underlying neurocognitive constructs. Together, latency on verbal WM tasks like the BDT may be a cognitive marker for emergent illness

Assessing working memory in mild cognitive impairment with serial order recall

Background: Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span subtest (BDT) only aggregate test performance was examined. The current research tallied primacy/ recency effects; out-of-sequence transposition errors; perseverations and omissions to assess WM deficits in patients with mild cognitive impairment (MCI). Methods: Memory clinic patients (n= 66) were classified into three groups - single domain amnestic MCI (aMCI), combined mixed domain/ dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/ WM ability was assessed by asking participants to repeat 7 trials of five digits backwards. Serial order position accuracy, transposition errors, perseverations, and omission errors were tallied. Results: A 3 (group) x 5 (serial position) repeated measures ANOVA yielded a significant group x trial interaction. Follow-up analyses found an absence of a recency effect for mixed/dys MCI patients. Mixed/dys MCI patients scored lower than non-MCI patients for serial position 3 (p \u3c 0.003) serial position 4 (p \u3c 0.002); and lower than both group for serial position 5 (recency; p \u3c 0.002). Mixed/dys MCI patients produced more transposition errors than both groups (p \u3c 0.010); and more omissions (p \u3c 0.020), and perseverations errors (p \u3c 0.018) than non-MCI patients. Conclusions: The striking absence and/ or attenuation of a recency effect using serial order parameters obtained from the BDT may constitute a neurocognitive biomarker for WM deficits in MCI and provide additional diagnostic information regarding working memory deficits in MCI

APOE4 is associated with cognitive and pathological heterogeneity in patients with Alzheimer’s disease: a systematic review

Possession of the ε4 allele of apolipoprotein E (APOE) is the primary genetic risk factor for the sporadic form of Alzheimer’s disease (AD). While researchers have extensively characterized the impact that APOE ε4 (APOE4) has on the susceptibility of AD, far fewer studies have investigated the phenotypic differences of patients with AD who are APOE4 carriers vs. those who are non-carriers. In order to understand these differences, we performed a qualitative systematic literature review of the reported cognitive and pathological differences between APOE4-positive (APOE4+) vs. APOE4-negative (APOE4−) AD patients. The studies performed on this topic to date suggest that APOE4 is not only an important mediator of AD susceptibility, but that it likely confers specific phenotypic heterogeneity in AD presentation, as well. Specifically, APOE4+ AD patients appear to possess more tau accumulation and brain atrophy in the medial temporal lobe, resulting in greater memory impairment, compared to APOE4− AD patients. On the other hand, APOE4− AD patients appear to possess more tau accumulation and brain atrophy in the frontal and parietal lobes, resulting in greater impairment in executive function, visuospatial abilities, and language, compared to APOE4+ AD patients. Although more work is necessary to validate and interrogate these findings, these initial observations of pathological and cognitive heterogeneity between APOE4+ vs. APOE4− AD patients suggest that there is a fundamental divergence in AD manifestation related to APOE genotype, which may have important implications in regard to the therapeutic treatment of these two patient populations

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

Dissociating Statistically Determined Normal Cognitive Abilities and Mild Cognitive Impairment Subtypes with DCTclock.

OBJECTIVE: To determine whether the DCTclock can detect differences across groups of patients seen in the memory clinic for suspected dementia. METHOD: Patients (n = 123) were classified into the following groups: cognitively normal (CN), subtle cognitive impairment (SbCI), amnestic cognitive impairment (aMCI), and mixed/dysexecutive cognitive impairment (mx/dysMCI). Nine outcome variables included a combined command/copy total score and four command and four copy indices measuring drawing efficiency, simple/complex motor operations, information processing speed, and spatial reasoning. RESULTS: Total combined command/copy score distinguished between groups in all comparisons with medium to large effects. The mx/dysMCI group had the lowest total combined command/copy scores out of all groups. The mx/dysMCI group scored lower than the CN group on all command indices ( CONCLUSIONS: These results suggest that DCTclock command/copy parameters can dissociate CN, SbCI, and MCI subtypes. The larger effect sizes for command clock indices suggest these metrics are sensitive in detecting early cognitive decline. Additional research with a larger sample is warranted

Visual and Verbal Serial List Learning in Patients with Statistically-Determined Mild Cognitive Impairment.

Background and Objective: Prior research with patients with mild cognitive impairment (MCI) suggests that visual versus verbal episodic memory test performance may be more sensitive to emergent illness. However, little research has examined visual versus verbal episodic memory performance as related to MCI subtypes. Research Design and Methods: Patients were diagnosed with non-MCI, amnestic MCI (aMCI), and combined mixed/dysexecutive MCI (mixed/dys MCI). Visual and verbal episodic memory were assessed with the Brief Visuospatial Memory Test-Revised (BVMT-R) and the 12-word Philadelphia (repeatable) Verbal Learning Test (P[r]VLT), respectively. Results: BVMT-R and P(r)VLT scores yielded similar between-group patterns of performance. Non-MCI patients scored better than other groups on all parameters. aMCI and mixed/dys MCI did not differ on immediate or delayed free recall. Both delayed BVMT-R and P(r)VLT recognition test performance dissociated all three groups. Logistic regression analyses found that BVMT-R delayed free recall and delayed recognition scores correctly classified more patients with MCI (75.40%) than analogous P(r)VLT scores (66.20%). Visual versus verbal memory within-group analyses found no differences among non-MCI patients; P(r)VLT immediate free recall was worse among aMCI patients, but BVMT-R immediate free recall and delayed recognition were worse among mixed/dys MCI patients. Discussion and Implications: Between-group analyses found convergent patterns of performance such that both tests identified elements of amnesia. However, logistic and within-group analyses found differing performance patterns suggesting that impaired visual episodic memory performance may be specific to emergent illness in mixed/dys MCI. Complementary but divergent neurocognitive networks may underlie visual versus verbal episodic memory performance in some patients with MCI

Assessing Working Memory in Mild Cognitive Impairment with Serial Order Recall.

BACKGROUND: Working memory (WM) is often assessed with serial order tests such as repeating digits backward. In prior dementia research using the Backward Digit Span Test (BDT), only aggregate test performance was examined. OBJECTIVE: The current research tallied primacy/recency effects, out-of-sequence transposition errors, perseverations, and omissions to assess WM deficits in patients with mild cognitive impairment (MCI). METHODS: Memory clinic patients (n = 66) were classified into three groups: single domain amnestic MCI (aMCI), combined mixed domain/dysexecutive MCI (mixed/dys MCI), and non-MCI where patients did not meet criteria for MCI. Serial order/WM ability was assessed by asking participants to repeat 7 trials of five digits backwards. Serial order position accuracy, transposition errors, perseverations, and omission errors were tallied. RESULTS: A 3 (group)×5 (serial position) repeated measures ANOVA yielded a significant group×trial interaction. Follow-up analyses found attenuation of the recency effect for mixed/dys MCI patients. Mixed/dys MCI patients scored lower than non-MCI patients for serial position 3 (p \u3c 0.003) serial position 4 (p \u3c 0.002); and lower than both group for serial position 5 (recency; p \u3c 0.002). Mixed/dys MCI patients also produced more transposition errors than both groups (p \u3c 0.010); and more omissions (p \u3c 0.020), and perseverations errors (p \u3c 0.018) than non-MCI patients. CONCLUSIONS: The attenuation of a recency effect using serial order parameters obtained from the BDT may provide a useful operational definition as well as additional diagnostic information regarding working memory deficits in MCI

Affective Disturbance in Mild Cognitive Impairment

Mild cognitive impairment (MCI) is an identifiable, prodromal stage of cognitive impairment and has been further defined into subtypes: amnestic, language, executive functioning, and multi domain/mixed MCI (Jak et al. 2009 ). The purpose of this study is to (1) examine the differences in depression, anxiety, and apathy between MCI subtypes; and (2) assess the relationship between the neurocognitive domains (executive functioning, language, and memory and affective symptoms. We hypothesize that apathy will be greater in dysexecutive/mixed MCI (dys/mixed MCI) and be more highly correlated to neurocognitive deficits compared to depression or anxiety. This is a retrospective study of 113 patients from the New Jersey Institute for Successful Aging Memory Assessment Program ( MAP). Affective symptoms of depression, anxiety, and apathy were assessed by caregiver report using the Neuropsychiatric Inventory (NPI). Anxiety was found to be higher in the aMCI group compared to the other two groups but did not show a significant relationship with memory on cognitive testing. Only apathy was related to deficits in the executive function cognitive domain and in processing speed. The findings suggest that evidence of these affective disturbances in a clinical setting warrants assessment of cognitive function