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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 < 0.003) serial position 4 (p < 0.002); and lower than both group for serial position 5 (recency; p < 0.002). Mixed/dys MCI patients also produced more transposition errors than both groups (p < 0.010); and more omissions (p < 0.020), and perseverations errors (p < 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. [ABSTRACT FROM AUTHOR]

Biomarker definitions for preclinical Alzheimer’s disease (AD) have identified individuals with neurodegeneration (ND+) without β-amyloidosis (Aβ-) and labeled them with suspected non-AD pathophysiology (SNAP). We evaluated Apolipoprotein E (APOE) ε2 and ε4 allele frequencies across biomarker definitions—Aβ-/ND- (n = 268), Aβ+/ND- (n = 236), Aβ-/ND+ or SNAP (n = 78), Aβ+/ND+ (n = 204)—hypothesizing that SNAP would have an APOE profile comparable to Aβ-/ND-. Using AD Neuroimaging Initiative data (n = 786, 72±7 years, 48% female), amyloid status (Aβ+ or Aβ-) was defined by cerebrospinal fluid (CSF) Aβ-42 levels, and neurodegeneration status (ND+ or ND-) was defined by hippocampal volume from MRI. Binary logistic regression related biomarker status to APOE ε2 and ε4 allele carrier status, adjusting for age, sex, education, and cognitive diagnosis. Compared to the biomarker negative (Aβ-/ND-) participants, higher proportions of ε4 and lower proportions of ε2 carriers were observed among Aβ+/ND- (ε4: OR = 6.23, p<0.001; ε2: OR = 0.53, p = 0.03) and Aβ+/ND+ participants (ε4: OR = 12.07, p<0.001; ε2: OR = 0.29, p = 0.004). SNAP participants were statistically comparable to biomarker negative participants (p-values>0.30). In supplemental analyses, comparable results were observed when coding SNAP using amyloid imaging and when using CSF tau levels. In contrast to APOE, a polygenic risk score for AD that excluded APOE did not show an association with amyloidosis or neurodegeneration (p-values>0.15), but did show an association with SNAP defined using CSF tau (β = 0.004, p = 0.02). Thus, in a population with low levels of cerebrovascular disease and a lower prevalence of SNAP than the general population, APOE and known genetic drivers of AD do not appear to contribute to the neurodegeneration observed in SNAP. Additional work in population based samples is needed to better elucidate the genetic contributors to various etiological drivers of SNAP. [ABSTRACT FROM AUTHOR]

Background: APOE‐ε4 is the strongest common genetic risk factor for Alzheimer's disease (AD) and contributes to worse cognition. However, many carriers of the APOE‐ε4 allele remain cognitively normal throughout life, suggesting resilience factors may exist that protect the brain. We leverage a unique statistical design to identify modifiers of APOE effects on cognition by first discovering gene modifiers leveraging RNA sequencing (RNAseq) from whole blood and then replicating any observed modifiers with brain RNAseq from an independent cohort. Transcripts that modify the association between APOE and cognitive decline may highlight pathways of risk or resilience that could be repurposed as targets for intervention. Method: Cognition, RNAseq from whole blood, and APOE genotype were obtained from 336 individuals from the Vanderbilt Memory and Aging Project (VMAP; mean(SD) age=72.9(7.3), % male=59, % mild cognitive impairment=39). RNAseq data were quantile normalized and batch corrected. Regression and mixed‐effects regression models assessed the interaction between baseline gene expression and APOE‐ε4 or APOE‐ε2 positivity on both baseline and longitudinal decline in memory, adjusting for baseline age and sex. Results were replicated using bulk dorsolateral prefrontal cortex RNAseq data in 618 participants from the Religious Orders Study/Memory and Aging Project (ROS/MAP). Results were corrected for multiple comparisons (60,669 genes) using the false discovery rate method. Results: Cross‐sectionally, RNASE6 interacted with APOE‐ε4 status on memory (β=‐1.16, p=4.35x10‐8) whereby low RNASE6 expression was associated with better memory performance at baseline among APOE‐ε4 carriers, but high RNASE6 expression was associated with worse memory performance among APOE‐ε4 carriers (Figure 1). These results replicated in brain RNAseq data from ROS/MAP (β=‐0.2, p=0.0009, Figure 2). There were no significant interactions longitudinally or with APOE‐ε2. Conclusion: RNASE6 encodes a protein involved in innate immunity, including antimicrobial and antiviral activity. It has not been previously associated with AD or AD‐related cognitive decline, though it has been identified in a co‐expression network module with other inflammatory genes, such as TYROBP (DAP12), previously linked to AD. Together, these data implicate neuroinflammatory regulation in cognitive decline, and suggest that innate immune signaling may contribute to the regulation of resilience and susceptibility to AD among APOE‐ε4 carriers. [ABSTRACT FROM AUTHOR]

A symptom of mild cognitive impairment (MCI) and Alzheimer’s disease (AD) is a flat learning profile. Learning slope calculation methods vary, and the optimal method for capturing neuroanatomical changes associated with MCI and early AD pathology is unclear. This study cross-sectionally compared four different learning slope measures from the Rey Auditory Verbal Learning Test (simple slope, regression-based slope, two-slope method, peak slope) to structural neuroimaging markers of early AD neurodegeneration (hippocampal volume, cortical thickness in parahippocampal gyrus, precuneus, and lateral prefrontal cortex) across the cognitive aging spectrum [normal control (NC); (n=198; age=76±5), MCI (n=370; age=75±7), and AD (n=171; age=76±7)] in ADNI. Within diagnostic group, general linear models related slope methods individually to neuroimaging variables, adjusting for age, sex, education, and APOE4 status. Among MCI, better learning performance on simple slope, regression-based slope, and late slope (Trial 2–5) from the two-slope method related to larger parahippocampal thickness (all p-values<.01) and hippocampal volume (p<.01). Better regression-based slope (p<.01) and late slope (p<.01) were related to larger ventrolateral prefrontal cortex in MCI. No significant associations emerged between any slope and neuroimaging variables for NC (p-values ≥.05) or AD (p-values ≥.02). Better learning performances related to larger medial temporal lobe (i.e., hippocampal volume, parahippocampal gyrus thickness) and ventrolateral prefrontal cortex in MCI only. Regression-based and late slope were most highly correlated with neuroimaging markers and explained more variance above and beyond other common memory indices, such as total learning. Simple slope may offer an acceptable alternative given its ease of calculation. (JINS, 2015, 21, 455–467) [ABSTRACT FROM AUTHOR]

The clinical relevance of gray/white matter contrast ratio (GWR) in mild cognitive impairment (MCI) remains unknown. This study examined baseline GWR and 3-year follow-up diagnostic status in MCI. Alzheimer's Disease Neuroimaging Initiative MCI participants with baseline 1.5 T MRI and 3-year follow-up clinical data were included. Participants were categorized into two groups based on 3-year follow-up diagnoses: 1) non-converters ( n = 69, 75 ± 7, 26 % female), and 2) converters (i.e., dementia at follow-up; n = 69, 75 ± 7, 30 % female) who were matched on baseline age and Mini-Mental State Examination scores. Groups were compared on FreeSurfer generated baseline GWR from structural images in which higher values represent greater tissue contrast. A general linear model, adjusting for APOE-status, scanner type, hippocampal volume, and cortical thickness, revealed that converters evidenced lower GWR values than non-converters (i.e., more degradation in tissue contrast; p = 0.03). Individuals with MCI who convert to dementia have lower baseline GWR values than individuals who remain diagnostically stable over a 3-year period, statistically independent of cortical thickness or hippocampal volume. [ABSTRACT FROM AUTHOR]

Background: A cognitive concern from the patient, informant, or clinician is required for the diagnosis of mild cognitive impairment (MCI); however, the cognitive and neuroanatomical correlates of complaint are poorly understood. Objective: We assessed how self-complaint relates to cognitive and neuroimaging measures in older adults with MCI. Method: MCI participants were drawn from the Alzheimer's Disease Neuroimaging Initiative and dichotomized into two groups based on the presence of self-reported memory complaint (no complaint n = 191, 77 ± 7 years; complaint n = 206, 73 ± 8 years). Cognitive outcomes included episodic memory, executive functioning, information processing speed, and language. Imaging outcomes included regional lobar volumes (frontal, parietal, temporal, cingulate) and specific medial temporal lobe structures (hippocampal volume, entorhinal cortex thickness, parahippocampal gyrus thickness). Results: Linear regressions, adjusting for age, gender, race, education, Mini-Mental State Examination score, mood, and apolipoprotein E4 status, found that cognitive complaint related to immediate (β = -1.07, p < 0.001) and delayed episodic memory performances assessed on a serial list learning task (β = -1.06, p = 0.001) but no other cognitive measures or neuroimaging markers. Conclusions: Self-reported memory concern was unrelated to structural neuroimaging markers of atrophy and measures of information processing speed, executive functioning, or language. In contrast, subjective memory complaint related to objective verbal episodic learning performance. Future research is warranted to better understand the relation between cognitive complaint and surrogate markers of abnormal brain aging, including Alzheimer's disease, across the cognitive aging spectrum. [ABSTRACT FROM AUTHOR]

Background: The relation between the source of cognitive complaint and objective cognitive performance is not well understood. Objective: Examine self and informant cognitive complaint as predictors of objective cognitive and functional trajectory in non-demented elders. Methods: Participants from the National Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC; n = 6133, 72 ± 8 years, 68% female) or mild cognitive impairment (MCI; n = 3010, 74 ± 8 years, 55% female). Four independent groups defined cognitive complaint: no complaint, self-only complaint, informant-only complaint, or mutual complaint (both self and informant complaint). Linear mixed model regression analyses related complaint status (referent was no complaint) to cognitive and functional trajectories, adjusting for age, sex, race, education, and follow-up period. Results: Among NC participants, mutual complaint related to faster decline in global cognition (p < 0.0001), language (all p-values <0.0001), processing speed (p = 0.0002), and executive functioning (p = 0.0006). Informant-only complaint related to faster decline in global cognition (p = 0.0001) and processing speed (p = 0.0001). Self-only complaint related to greater decline in immediate (p < 0.0001) and delayed (p = 0.0005) episodic memory. In MCI, mutual complaint related to faster decline in global cognition (p < 0.0001), verbal episodic memory (all p-values <0.0001), language (all p-values <0.0001), and processing speed (all p-values <0.0006). Informant-only or self-only complaint associations with cognitive trajectory did not survive correction factor for multiple comparisons. Conclusion: Cognitive complaint appears to have clinical significance, as it is related to declines in objective cognitive performance over time. Mutual complaint was associated with the worst cognitive trajectory in both NC and MCI elders, highlighting the importance of incorporating an informant into evaluation of elders whenever feasible. [ABSTRACT FROM AUTHOR]

Abstract: Objective: The objective of this study was to compare whether different sources of cognitive complaint (i.e., subjective and informant) predict diagnostic conversion in nondemented older adults. Methods: Participants from the National Alzheimer's Coordinating Center had a baseline diagnosis of normal cognition (NC; n = 4414; mean age, 73 ± 8 years; 69% female) or mild cognitive impairment (MCI; n = 1843; mean age, 74 ± 8 years; 52% female). Multinomial logistic regression related baseline cognitive complaint (no complaint, self only, informant only, or both self and informant) to diagnostic outcome (reversion, stable, or conversion). Results: At follow-up, 14% of NC participants converted to MCI/dementia (3.5 ± 1.8 years), and 41% of MCI participants converted to dementia (3.0 ± 1.6 years). Among NC participants, self complaint only (odds ratio [OR], 2.1; 99% confidence interval (CI),1.5–2.9; P < .001), informant complaint only (OR, 2.2; 99% CI, 1.2–3.9; P < .001), and both self and informant complaint (OR, 4.2; 99% CI, 2.9–6.0; P < .001) were associated with diagnostic conversion compared with no complaint. Among participants with MCI—compared with no complaint, informant complaint only (OR, 2.2; 99% CI, 1.2–4.3, P = .002), and both self and informant complaint (OR, 2.9; 99% CI, 1.8–4.8; P < .001)—were associated with conversion. Conclusions: Cognitive complaints are related to conversion among nondemented older adults. Complaint from both (i.e. mutual complaint) sources was most predictive of diagnostic outcome, followed by informant complaint, highlighting the need for obtaining informant corroboration to enhance prognosis and distinguish underlying pathological processes from normal cognitive aging. Self complaint was related inconsistently to diagnostic outcome. [Copyright &y& Elsevier]

The article presents a study which uses point counts in comparing habitat use of forest birds in native mixed-species forest of mature tallow trees and of young tallow trees on the coast of Texas. It compares bird communities of these habitats from 2009-2010 because previous studies has been focused on the nonbreeding season. Results show that tallow trees provide habitat for some forest birds in winter and recommends the preservation of native mixed-species forest.