Search

Background: Individuals with Alzheimer's disease (AD) often present with coexisting vascular pathology that is expressed to different degrees and can lead to clinical heterogeneity., Objective: To examine the utility of unsupervised statistical clustering approaches in identifying neuropsychological (NP) test performance subtypes that closely correlate with carotid intima-media thickness (cIMT) in midlife., Methods: A hierarchical agglomerative and k-means clustering analysis based on NP scores (standardized for age, sex, and race) was conducted among 1,203 participants (age 48±5.3 years) from the Bogalusa Heart Study. Regression models assessed the association between cIMT ≥50th percentile and NP profiles, and global cognitive score (GCS) tertiles for sensitivity analysis., Results: Three NP profiles were identified: Mixed-low performance [16%, n = 192], scores ≥1 SD below the mean on immediate, delayed free recall, recognition verbal memory, and information processing; Average [59%, n = 704]; and Optimal [26%, n = 307] NP performance. Participants with greater cIMT were more likely to have a Mixed-low profile [OR = 3.10, 95% CI (2.13, 4.53), p < 0.001] compared to Optimal. After adjusting for education and cardiovascular (CV) risks, results remained. The association with GCS tertiles was more attenuated [lowest (34%, n = 407) versus highest (33%, n = 403) tertile: adjusted OR = 1.66, 95% CI (1.07, 2.60), p = 0.024]., Conclusion: As early as midlife, individuals with higher subclinical atherosclerosis were more likely to be in the Mixed-low profile, underscoring the potential malignancy of CV risk as related to NP test performance, suggesting that classification approaches may aid in identifying those at risk for AD/vascular dementia spectrum illness.

Background: Trauma and depression have each been associated with neurocognitive alterations, but their combined effect on neurocognition is unclear. We investigated the separate and interactive associations of trauma and depression on neurocognition in a sample of ethnically diverse urban dwellers, and explored the impact of age on these effects., Methods: 284 adults aged 30-89 were divided into groups based on their current depression and trauma history. Individuals meeting DSM-IV criteria for depression were considered Depressed (D+) and individuals rated through diagnostic interview as having trauma history were considered positive for Trauma (T+). Resulting Ns were 73 D+T+, 56 D+T-, 68 D-T+, and 87 D-T-. A principal component analysis of neuropsychological scores resulted in a 3-factor solution representing verbal learning/memory/recognition (VERBAL-LMR), visual learning/memory/recognition, and speeded attention/cognitive flexibility accounting for 70.21% of the variance., Results: Multivariable linear regressions adjusting for age revealed that Trauma, regardless of Depression, is associated with worse VERBAL-LMR performance. This Trauma association was driven by verbal list and prose passages learning and memory, but not recognition memory. Age-stratified (<60 versus ≥60 years) regressions revealed the Trauma association was only significant for older adults. No main or interactive effects for Depression were observed., Conclusions: Trauma, regardless of Depression, is associated with worse verbal learning and memory, but not recognition performance. These results suggest that trauma exposure may negatively impact neurocognition. Clinicians working with adults in urban settings should query for trauma in addition to depression when considering subjective and objective measures of neurocognitive functioning, particularly in older adults., (Copyright © 2017 Elsevier Ltd. All rights reserved.)

Psychomotor slowing has been documented in depression. The digital Clock Drawing Test (dCDT) provides: (i) a novel technique to assess both cognitive and motor aspects of psychomotor speed within the same task and (ii) the potential to uncover subtleties of behavior not previously detected with non-digitized modes of data collection. Using digitized pen technology in 106 participants grouped by Age (younger/older) and Affect (euthymic/unmedicated depressed), we recorded cognitive and motor output by capturing how the clock is drawn rather than focusing on the final product. We divided time to completion (TTC) for Command and Copy conditions of the dCDT into metrics of percent of drawing (%Ink) versus non-drawing (%Think) time. We also obtained composite Z-scores of cognition, including attention/information processing (AIP), to explore associations of %Ink and %Think times to cognitive and motor performance. Despite equivalent TTC, %Ink and %Think Command times (Copy n.s.) were significant (AgeXAffect interaction: p=.03)-younger depressed spent a smaller proportion of time drawing relative to thinking compared to the older depressed group. Command %Think time negatively correlated with AIP in the older depressed group (r=-.46; p=.02). Copy %Think time negatively correlated with AIP in the younger depressed (r=-.47; p=.03) and older euthymic groups (r=-.51; p=.01). The dCDT differentiated aspects of psychomotor slowing in depression regardless of age, while dCDT/cognitive associates for younger adults with depression mimicked patterns of older euthymics.

Background: Total knee arthroplasty improves quality of life but is associated with postoperative cognitive dysfunction in older adults. This prospective longitudinal pilot study with a parallel control group tested the hypotheses that (1) nondemented adults would exhibit primary memory and executive difficulties after total knee arthroplasty, and (2) reduced preoperative hippocampus/entorhinal volume would predict postoperative memory change, whereas preoperative leukoaraiosis and lacunae volumes would predict postoperative executive dysfunction., Methods: Surgery (n = 40) and age-education-matched controls with osteoarthritis (n = 15) completed pre- and postoperative (3 weeks, 3 months, and 1 yr) memory and cognitive testing. Hypothesized brain regions of interest were measured in patients completing preoperative magnetic resonance scans (surgery, n = 31; control, n = 12). Analyses used reliable change methods to identify the frequency of cognitive change at each time point., Results: The incidence of postoperative memory difficulties was shown with delay test indices (i.e., story memory test: 3 weeks = 17%, 3 months = 25%, 1 yr = 9%). Postoperative executive difficulty with measures of inhibitory function (i.e., Stroop Color Word: 3 weeks = 21%, 3 months = 22%, 1 yr = 9%). Hierarchical regression analysis assessing the predictive interaction of group (surgery, control) and preoperative neuroanatomical structures on decline showed that greater preoperative volumes of leukoaraiosis/lacunae were significantly contributed to postoperative executive (inhibitory) declines., Conclusions: This pilot study suggests that executive and memory declines occur in nondemented adults undergoing orthopedic surgery. Severity of preoperative cerebrovascular disease may be relevant for understanding executive decline, in particular.

Background: Epidemiologic autopsy studies show mixed Alzheimer's disease (AD)/vascular pathology in many patients. Moreover, clinical research shows that it is not uncommon for AD and vascular dementia (VaD) patients to be equally impaired on memory, executive, or other neurocognitive tests. However, this clinical heterogeneity has not been incorporated into the new diagnostic criteria for AD (Dubois et al., 2010; McKhann et al., 2011)., Objective: The current research applied Latent Class Analysis (LCA) to a protocol of six neuropsychological parameters to identify phenotypic subtypes from a large group of AD/VaD participants. Follow-up analyses examined difference between groups on neuroradiological parameters and neuropsychological measures of process and errors., Methods: 223 AD/VaD patients were administered a comprehensive neuropsychological protocol. Measures of whole brain and hippocampal volume were available for a portion of the sample (n = 76)., Results: LCA identified four distinct groups: moderate/mixed dementia (n = 54; 24.21%), mild/mixed dementia (n = 91; 40.80%); dysexecutive (n = 49, 21.97%), and amnestic (n = 29, 13.00%). Follow-up analyses comparing the groups on neuropsychological process and error scores showed that the dysexecutive group exhibited difficulty sustaining mental set. The moderate/mixed group evidenced pronounced impairment on tests of lexical retrieval/naming along with significant amnesia. Amnestic patients also presented with gross amnesia, but showed relative sparing on other neuropsychological measures. Mild/mixed patients exhibited milder memory deficits that were intermediary between the amnestic and moderate/mixed groups., Conclusions: There are distinct neuropsychological profiles in patients independent of clinical diagnosis, suggesting that the two are not wholly separate and that this information should be integrated into new AD diagnostic paradigms.

Background: Vascular risk factors have been associated with cognitive decline; however, it remains unclear whether apolipoprotein E (APOE) genotype modifies this relationship. We aimed to further elucidate these relationships and extend previous findings by examining data from a more comprehensive cognitive assessment than used in prior studies., Methods: In all, 1436 participants from the prospective Framingham Offspring Cohort Study underwent health examination from 1991 to 1995, followed by a baseline neuropsychological assessment (1999-2003) and a repeat neuropsychological assessment approximately 8 years later (2004-2009). Multivariate linear regression analyses were performed to examine the relationship among midlife vascular risk factors, presence of the APOE ε4 allele, and cognitive change., Results: APOE genotype significantly modified the associations between both midlife hypertension and cardiovascular disease and decline in language abilities and midlife diabetes and decline in verbal memory, attention, and visuospatial abilities. Associations between increased midlife vascular risk burden and greater cognitive decline were observed among APOE ε4 carriers but not noncarriers., Conclusions: The present findings revealed a subgroup at increased risk for cognitive decline (APOE ε4 carriers with midlife exposure to vascular risk factors) and suggest that treatment of vascular risk factors during midlife may reduce the risk of cognitive impairment later in life, particularly among APOE ε4 carriers., (Copyright © 2013 National Stroke Association. Published by Elsevier Inc. All rights reserved.)

Background: Significant heterogeneity in clinical features of frontotemporal lobar degeneration (FTLD) and amyotrophic lateral sclerosis (ALS) cases with the pathogenic C9orf72 expansion (C9P) have been described. To clarify this issue, we compared a large C9P cohort with carefully matched non-expansion (C9N) cases with a known or highly-suspected underlying TAR DNA-binding protein 43 (TDP-43) proteinopathy., Methods: A retrospective case-control study was carried out using available cross-sectional and longitudinal clinical and neuropsychological data, MRI voxel-based morphometry (VBM) and neuropathological assessment from 64 C9P cases (ALS=31, FTLD=33) and 79 C9N cases (ALS=36, FTLD=43)., Results: C9P cases had an earlier age of onset (p=0.047) and, in the subset of patients who were deceased, an earlier age of death (p=0.014) than C9N. C9P had more rapid progression than C9N: C9P ALS cases had a shortened survival (2.6 ± 0.3 years) compared to C9N ALS (3.8 ± 0.4 years; log-rank λ2=4.183, p=0.041), and C9P FTLD showed a significantly greater annualised rate of decline in letter fluency (4.5 ± 1.3 words/year) than C9N FTLD (1.4 ± 0.8 words/year, p=0.023). VBM revealed greater atrophy in the right frontoinsular, thalamus, cerebellum and bilateral parietal regions for C9P FTLD relative to C9N FTLD, and regression analysis related verbal fluency scores to atrophy in frontal and parietal regions. Neuropathological analysis found greater neuronal loss in the mid-frontal cortex in C9P FTLD, and mid-frontal cortex TDP-43 inclusion severity correlated with poor letter fluency performance., Conclusions: C9P cases may have a shorter survival in ALS and more rapid rate of cognitive decline related to frontal and parietal disease in FTLD. C9orf72 genotyping may provide useful prognostic and diagnostic clinical information for patients with ALS and FTLD.

This study examined everyday action impairment in participants with Parkinson's disease dementia (PDD) by comparison with participants with Parkinson's disease-no dementia (PD) or Alzheimer's disease (AD) and in reference to a neuropsychological model. Participants with PDD (n = 20), PD (n = 20), or AD (n = 20) were administered performance-based measures of everyday functioning that allowed for the quantification of overall performance and error types. Also, caregiver ratings of functional independence were obtained. On performance-based tests, the PDD group exhibited greater functional impairment than the PD group but comparable overall impairment relative to the AD group. Error patterns did not differ between PDD and PD participants but the PDD group demonstrated a higher proportion of commission errors and lower proportion of omission errors relative to the AD group. Hierarchical regression analyses showed omission errors were significantly predicted by neuropsychological measures of episodic memory, whereas commission errors were predicted by both measures of general dementia severity (MMSE) and executive control. Everyday action impairment in PDD differs quantitatively from PD but qualitatively from AD and may be characterized by a relatively high proportion of commission errors-an error type associated with executive control deficits. (JINS, 2012, 18, 1-12).

Objective: Amyotrophic Lateral Sclerosis (ALS) is associated with impaired executive control. The aim of the current research was to test the hypothesis that concept formation deficits associated with an extramotor neurocognitive network involving executive and semantic resources can be found in some ALS patients., Method: Forty-one patients with clinically definite ALS were assessed with Delis Kaplan Executive Function System Sorting Test (D-KEFS), a measure of concept formation requiring patients to manipulate verbal and visual semantic information and neuropsychological tests measuring naming, semantic memory, and executive control. Using D-KEFS scale scores, a k-mean cluster analysis specifying a 3-group solution was able to classify ALS patients into groups presenting with mildly impaired, average, and above average sorting test performance. High-resolution T1 structural MRI was used to examine cortical thickness in a subset of 16 ALS patients., Results: Stepwise regression analyses related free and recognition sorting test performance to measures of action naming, single word semantic knowledge, and mental search/working memory. MRI studies found widespread cortical thinning involving bilateral frontal, temporal, and parietal regions. Regression analyses related recognition sorting performance to reduced MRI cortical thickness involving the left prefrontal and left parietal cortex., Conclusions: An extramotor cognitive network is associated with impaired concept formation in ALS.

Libon et al. (2010) provided evidence for three statistically determined clusters of patients with mild cognitive impairment (MCI): amnesic (aMCI), dysexecutive (dMCI), and mixed (mxMCI). The current study further examined dysexecutive impairment in MCI using the framework of Fuster's (1997) derailed temporal gradients, that is, declining performance on executive tests over time or test epoch. Temporal gradients were operationally defined by calculating the slope of aggregate letter fluency output across 15-s epochs and accuracy indices for initial, middle, and latter triads from the Wechsler Memory Scale-Mental Control subtest (Boston Revision). For letter fluency, slope was steeper for dMCI compared to aMCI and NC groups. Between-group Mental Control analyses for triad 1 revealed worse dMCI performance than NC participants. On triad 2, dMCI scored lower than aMCI and NCs; on triad 3, mxMCI performed worse versus NCs. Within-group Mental Control analyses yielded equal performance across all triads for aMCI and NC participants. mxMCI scored lower on triad 1 compared to triads 2 and 3. dMCI participants also performed worse on triad 1 compared to triads 2 and 3, but scored higher on triad 3 versus triad 2. These data suggest impaired temporal gradients may provide a useful heuristic for understanding dysexecutive impairment in MCI.

The well-established association between advanced age, cerebrovascular pathology, and cognitive decline is receiving greater attention as the population attains new levels of longevity. This chapter will provide an overview of vascular anatomy and age-related cerebrovascular disorders and diseases, including stroke and degenerative dementia. The cognitive and functional sequellae of these cerebrovascular disorders will also be described in detail. Throughout this review, we will emphasize topics that have been relatively underrepresented in the literature, including age-related diseases of the cerebral small vessels, nuanced characterization of cognitive impairment associated with insidious small-vessel vascular dementia, and the real-life functional consequences of cerebrovascular changes in older adults.

The Philadelphia Brief Assessment of the Cognition (PBAC) is a brief dementia-screening instrument. The PBAC assesses five cognitive domains: working memory/executive control; lexical retrieval/language; visuospatial/visuoconstructional operations; verbal/visual episodic memory; and behavior/social comportment. A revised version of the PBAC was administered to 198 participants including patients with Alzheimer's disease (AD) (n=46) and four groups of patients with frontotemporal dementia (FTD) syndromes: behavioral-variant FTD (bvFTD; n=65), semantic-variant primary progressive aphasia (PPA) (svPPA; n=22), non-fluent/agrammatic-variant PPA (nfaPPA; n=23), and corticobasal syndrome (CBS; n=42), and a group of normal controls (n=15). The total PBAC score was highly correlated with the MMSE. The criterion validity of the PBAC was assessed relative to standard neuropsychological test performance. Using standard neuropsychological test performance as a criterion, the total PBAC score accurately identified the presence and severity of dementia. Intra-class correlations between PBAC subscales and standard neuropsychological tests were highly significant. PBAC subscales demonstrated good clinical utility in distinguishing AD and FTD subtypes using receiver operating characteristic analysis and standard diagnostic performance statistics to determine optimal subscale cut scores. The PBAC is a valid tool and able to assesses differential patterns neuropsychological/behavioral impairment in a broad range of neurodegenerative conditions.

Using cluster analysis Libon et al. (2010) found three verbal serial list-learning profiles involving delay memory test performance in patients with mild cognitive impairment (MCI). Amnesic MCI (aMCI) patients presented with low scores on delay free recall and recognition tests; mixed MCI (mxMCI) patients scored higher on recognition compared to delay free recall tests; and dysexecutive MCI (dMCI) patients generated relatively intact scores on both delay test conditions. The aim of the current research was to further characterize memory impairment in MCI by examining forgetting/savings, interference from a competing word list, intrusion errors/perseverations, intrusion word frequency, and recognition foils in these three statistically determined MCI groups compared to normal control (NC) participants. The aMCI patients exhibited little savings, generated more highly prototypic intrusion errors, and displayed indiscriminate responding to delayed recognition foils. The mxMCI patients exhibited higher saving scores, fewer and less prototypic intrusion errors, and selectively endorsed recognition foils from the interference list. dMCI patients also selectively endorsed recognition foils from the interference list but performed similarly compared to NC participants. These data suggest the existence of distinct memory impairments in MCI and caution against the routine use of a single memory test score to operationally define MCI.

We sought to elucidate the existence of neuropsychological subtypes in Complex Regional Pain Syndrome (CRPS). One hundred thirty seven patients with CRPS were administered tests that assess executive control, naming/lexical retrieval, and declarative memory. A 2-step cluster analysis that does not require any a priori specification regarding the number of clusters, classified patients into three groups. Group 1 obtained scores that were in the average range on all tests (n = 48; normal CRSP group). Group 2 (n = 58; dysexecutive CRSP group) presented with mild impairment or statistically low average test performance on working memory/verbal fluency tests. Group 3 (n = 31; global CRSP group) produced scores in the statistically low average/borderline range on all tests with particularly reduced scores on naming/declarative memory tests. Between-group analyses found that the CRPS group 1 obtained higher scores than CRPS groups 2 and 3 on all tests. However, groups 2 and 3 were equally impaired on executive tests. CRPS group 3 was impaired on tests of naming/memory tests compared to the other groups. Significant neuropsychological deficits are present in 65% of patients, with many patients presenting with elements of a dysexecutive syndrome and some patients presenting with global cognitive impairment.

Objective: To investigate the cognitive and neural correlates of discourse impairment in corticobasal syndrome (CBS)., Background: Difficulty communicating is a frequent clinical manifestation in patients with CBS. However, the mechanisms underlying this disabling problem are not well understood., Methods: Twenty patients with CBS and 8 healthy seniors narrated a picture story. Narratives were analyzed for maintenance of the narrative theme, identification of the overall point of the story (global connectedness), and connectedness between consecutive events (local connectedness). Discourse measures were correlated with performance on cognitive tasks and with cortical atrophy as determined by magnetic resonance imaging voxel-based morphometry., Results: Patients with CBS referred to the narrative theme significantly less frequently than controls. Global connectedness was intact in only 6 of 20 CBS patients (30%), but preserved in all controls. Local connectedness was significantly diminished in patients relative to controls. Discourse performance in CBS was related to tasks requiring higher-order integration of visual material, but not to basic visuospatial/visuoperceptual, language, or memory function. Discourse impairment was directly related to atrophy in the right parietal lobe and bilateral dorsolateral prefrontal cortex., Conclusions: Our findings suggest that impaired information integration in CBS, related to parieto-frontal disease, interferes with patients' ability to narrate a coherent story.

The longitudinal assessment of episodic and semantic memory was obtained from 236 patients diagnosed with Alzheimer's disease (AD, n = 128) and with frontotemporal lobar degeneration (FTLD, n = 108), including patients with a social comportment/dysexecutive (SOC/EXEC) disorder, progressive nonfluent aphasia (PNFA), semantic dementia (SemD), and corticobasal syndrome (CBS). At the initial assessment, AD patients obtained a lower score on the delayed free recall test than other patients. Longitudinal analyses for delayed free recall found converging performance, with all patients reaching the same level of impairment as AD patients. On the initial evaluation for delayed recognition, AD patients also obtained lower scores than other groups. Longitudinal analyses for delayed recognition test performance found that AD patients consistently produced lower scores than other groups and no convergence between AD and other dementia groups was seen. For semantic memory, there were no initial between-group differences. However, longitudinal analyses for semantic memory revealed group differences over illness duration, with worse performance for SemD versus AD, PNFA, SOC/EXEC, and CBS patients. These data suggest the presence of specific longitudinal patterns of impairment for episodic and semantic memory in AD and FTLD patients suggesting that all forms of dementia do not necessarily converge into a single phenotype.

A group of 94 nondemented patients self-referred to an outpatient memory clinic for memory difficulties were studied to determine the incidence of single versus multi-domain mild cognitive impairment (MCI) using Petersen criteria. Fifty-five community dwelling normal controls (NC) participants without memory complaints also were recruited. Tests assessing executive control, naming/lexical retrieval, and declarative memory were administered. Thirty-four patients exhibited single-domain MCI, 43 patients presented with multi-domain MCI. When the entire MCI sample (n = 77) was subjected to a cluster analysis, 14 patients were classified with amnesic MCI, 21 patients with dysexecutive MCI, and 42 patients were classified into a mixed/multi-domain MCI group involving low scores on tests of letter fluency, "animal" fluency, and delayed recognition discriminability. Analyses comparing the three cluster-derived MCI groups versus a NC group confirmed the presence of memory and dysexecutive impairment for the amnesic and dysexecutive MCI groups. The mixed MCI group produced lower scores on tests of letter fluency compared with the amnesic MCI and NC groups and lower scores on tests of naming and memory compared with the NC group. In summary, multi-domain MCI is quite common. These data suggest that MCI is a highly nuanced and complex clinical entity.

The introduction of diagnostic criteria for vascular dementia has helped to re-define the impact of various subcortical neuropathologies on aging; however, state-of-the-art neuroimaging techniques and autopsy studies suggest that not all structural brain alterations associated with vascular dementia are exclusive to this neurodegenerative process alone. Thus, a detailed analysis of the cognitive phenotype associated with ischaemic vascular disease is key to our understanding of subcortical neuropathology and its associated behaviors. Over the past twenty years, we have operationally defined this cognitive phenotype using the Boston Process Approach to neuropsychological assessment. This has led to both an empirical, as well as a theoretical understanding of three core constructs related to the dysexecutive syndrome associated with ischaemic vascular disease affecting periventricular and deep white matter as well as subcortical structures connecting these regions with the prefrontal cortex. Thus, difficulties with mental set, cognitive control and mental manipulation negatively impact executive functioning. This review will outline the subtle markers underlying this prefrontal dysfunction, i.e., the dysexecutive phenotype, associated with ischaemic vascular disease and relate it to fundamental impairments of gating subserved by basal ganglia-thalamic pathways within and across various dementia syndromes.

Recent evidence suggests that patients with Alzheimer's disease (AD) and vascular comorbidities (VC) perform worse across measures of verbal reasoning and abstraction when compared to patients with AD alone. We performed a qualitative error analysis of Wechsler Adult Intelligence Scale-III Similarities zero-point responses in 45 AD patients with varying numbers of VC, including diabetes, hypertension, and hypercholesterolemia. Errors were scored in set if the answer was vaguely related to how the word pair was alike (e.g., dog-lion: "they can be trained") and out of set if the response was unrelated ("a lion can eat a dog"). AD patients with 2-3 VC did not differ on Similarities total score or qualitative errors from AD patients with 0-1 VC. When analyzing the group as a whole, we found that increasing numbers of VC were significantly associated with increasing out of set errors and decreasing in set errors in AD. Of the vascular diseases investigated, it was only the severity of diastolic blood pressure that significantly correlated with out of set responses. Understanding the contribution of VC to patterns of impairment in AD may provide support for directed patient and caregiver education concerning the presentation of a more severe pattern of cognitive impairment in affected individuals.

This study examined whether distinct neuropsychological profiles could be delineated in a sample with Mild Cognitive Impairment (MCI) and whether white matter lesion (WML) burden contributed to MCI group differences. A heterogeneous, clinical sample of 70 older adults diagnosed with MCI was assessed using cognitive scores, and WML was quantified using a semi-automated, volumetric approach on T2-weighted fluid-attenuated inversion recovery (FLAIR) images. Using cluster and discriminant analyses, three distinct groups (Memory/Language, Executive/Processing Speed, and Pure Memory) were empirically derived based on cognitive scores. Results also showed a dose dependent relationship of WML burden to MCI subgroup, with the Executive/Processing Speed subgroup demonstrating significantly higher levels of WML pathology when compared to the other subgroups. In addition, there was a dissociation of lesion type by the two most impaired subgroups (Memory/Language and Executive/Processing Speed) such that the Memory/Language subgroup showed higher periventricular lesion (PVL) and lower deep white matter lesion (DWML) volumes, whereas the Executive/Processing Speed demonstrated higher DWML and lower PVL volumes. Results demonstrate that distinct MCI subgroups can be empirically derived and reliably differentiated from a heterogeneous MCI sample, and that these profiles differ according to WML burden. Overall, findings suggest different underlying pathologies within MCI and contribute to our understanding of MCI subtypes.

We hypothesized that specific neuropsychological deficits were associated with specific patterns of atrophy. A magnetic resonance imaging volumetric study and a neuropsychological protocol were obtained for patients with several frontotemporal lobar dementia phenotypes including a social/dysexecutive (SOC/EXEC, n = 17), progressive nonfluent aphasia (n = 9), semantic dementia (n = 7), corticobasal syndrome (n = 9), and Alzheimer's disease (n = 21). Blinded to testing results, patients were partitioned according to pattern of predominant cortical atrophy; our partitioning algorithm had been derived using seriation, a hierarchical classification technique. Neuropsychological test scores were regressed versus these atrophy patterns as fixed effects using the covariate total atrophy as marker for disease severity. The results showed the model accounted for substantial variance. Furthermore, the "large-scale networks" associated with each neuropsychological test conformed well to the known literature. For example, bilateral prefrontal cortical atrophy was exclusively associated with SOC/EXEC dysfunction. The neuropsychological principle of "double dissociation" was supported not just by such active associations but also by the "silence" of locations not previously implicated by the literature. We conclude that classifying patients with degenerative dementia by specific pattern of cortical atrophy has the potential to predict individual patterns of cognitive deficits.

Few studies have assessed whether the patterns of neuropsychological impairment in patients with different frontotemporal lobar degeneration (FTLD) subtypes remain distinct over the duration of their illness or devolve into a common, undifferentiated neuropsychological state. A longitudinal neuropsychological analysis was obtained over 100 months assessing executive control, language/naming, and visuoconstruction in 441 patients diagnosed with Alzheimer's disease (AD) and four FTLD subtypes, i.e., a social comportment/dysexecutive (SOC/EXEC) disorder; progressive non-fluent aphasia (PNFA); semantic dementia (SemD); and corticobasal degeneration (CBD). Initial group differences on each measure were maintained over the duration of illness, including several double dissociations. For example, AD patients exhibited a decline in 'animal' fluency; PNFA patients had difficulty on tests of executive control, SemD maintained their impairment on tests of naming, and CBD had presented with performance on visuoconstructional tests. None of the group by neuropsychological task interactions evaluating longitudinal decline was significant, suggesting that performance does not converge onto a common subtype over time. These data indicate that distinct patterns of neuropsychological impairment are maintained longitudinally, reflecting the unique anatomic distribution of relative disease burden in AD and FTLD.

Aims: To evaluate the degree and pattern of functional difficulties in mild cognitive impairment (MCI) via direct observation of everyday task performance., Methods: MCI (n = 25), mild Alzheimer's disease (AD; n = 25), and control (n = 18) participants performed three everyday tasks of increasing complexity., Results: Although caregivers reported no functional difficulties in MCI, direct observation measures of overall impairment and total errors showed MCI participants performed worse than controls, but better than AD participants, even on simple tasks. MCI and control participants exhibited significantly more difficulty performing steps accurately (i.e. commission errors) than completing task steps (i.e. omission errors), but AD participants showed an even distribution of commissions and omissions., Conclusions: Diagnostic criteria for MCI should specify mild functional deficits due to the inefficient and imprecise execution of task steps. Functional deficits characterized by omission of major task segments may indicate a diagnosis of dementia., ((c) 2008 S. Karger AG, Basel.)

Background: A neuropsychological screening instrument sensitive to neuropsychological deficits associated with Alzheimer's disease (AD) and patients with frontotemporal dementia (FTD) would be valuable for diagnostic evaluation., Methods: The Philadelphia Brief Assessment of Cognition (PBAC) assesses working memory/executive control, language, visuospatial operations, verbal/visual episodic memory, and behavior/social comportment and can be administered and scored in 15-20 min. Participants included 149 patients with AD and four groups of FTD patients - i.e., patients with a decline in social comportment, personality, and executive functioning (SOC/EXEC), semantic dementia (SemD), progressive nonfluent aphasia (PNFA), and corticobasal syndrome (CBS)., Results: The total PBAC score correlated with the Mini-Mental State Examination. Between-group analysis of PBAC subscales and the results of logistic regression analyses produced substantial between-group differences, emphasizing the sensitivity of the test to differentiate dementia subtypes. AD patients were impaired on tests of episodic memory, SOC/EXEC patients were impaired on a measure of social comportment/behavioral disturbance, PNFA patients obtained low scores on tests of working memory/executive control, SemD patients obtained lower scores on language-mediated measures, and CBS patients were impaired on visuospatial/visual memory tests., Conclusion: These data support the usefulness of the PBAC as a relatively brief screening test of overall dementia severity across a wide range of dementia patients., ((c) 2007 S. Karger AG, Basel.)

Differential patterns of executive function deficits (EFD) exist in cortical and subcortical dementia; however, little work exists attempting to integrate these findings into a conceptual framework. The current study aimed to characterize EFD in cortical and subcortical dementia. Patients with Alzheimer's disease (AD; n = 65), subcortical ischemic vascular dementia (IVD; n = 64), or Parkinson's disease with dementia (dPD; n = 21) completed a variety of measures purported to require executive systems. We extracted variables of interest from measures shown in a growing body of literature to be associated with EFD in dementia. These measures included the Boston Revision of the WMS Mental Control subtest, letter fluency, WAIS-R Similarities subtest, CVLT, the Graphical Sequence Test-Dementia version, and Clock Drawing. When submitted to a PCA with varimax rotation, these variables produced a four-component solution (62% of the variance). Component 1 appeared to reflect adequacy of working memory, Component 2 irrelevant or context nonspecific interference, Component 3 reflected response preparation and Component 4 relevant or context-specific interference. Post hoc analyses of z-transformed composite scores revealed that AD differentially affected context-specific interference, IVD and dPD disrupted working memory and response preparation while IVD differentially affected context non-specific interference. EFD in dementia can be divided into specific components that are differentially impaired by cortical and subcortical dementias. Implications for an overall conceptual framework of EFD in dementia are discussed.

Clinical methods used to determine unawareness in dementia exist; however, their applicability to empirical research is limited. The authors present a statistically derived approach to determining unawareness that addresses these limitations. Dementia patients (n=32) completed an awareness questionnaire. On an identical questionnaire, collateral sources (relatives or friends; n=32) provided their best estimate of participants' abilities. The authors compared cluster analysis, the proposed empirical approach, to a currently used standard deviation cutoff score approach. Cluster analysis included all participants, displayed sound statistical properties, and was more sensitive to between-group differences in psychotic symptoms than standard deviation cutoff. Cluster analysis appears more appropriate for understanding the overall spectrum of unawareness in dementia research.

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 (p  < .050, all analyses); and lower than the SbCI group on drawing efficiency (p  = .011). The aMCI group scored lower than the CN group on spatial reasoning (p  = .019). Smaller effect sizes were obtained for the four copy 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. [ABSTRACT FROM AUTHOR]

Objective: Cognitive tests requiring spoken responses, such as paragraph recall, are rich in cognitive-related information that is not captured using traditional scoring methods. This study aimed to determine if linguistic features embedded in spoken responses may differentiate between individuals who are and are not cognitively impaired. Participants and Methods: Participants in the Long Life Family Study completed a neuropsychological assessment which included the WMS-R Logical Memory I paragraph recall. For a subset of participants (N=709), test responses were digitally recorded and manually transcribed. We used Linguistic Inquiry Word Count, a text analysis program, to quantify word counts, grammatical features (e.g, prepositions, verb tenses), and the use of content words related to specific semantic categories (e.g., work-related, numbers) for immediate (IR) and delayed recall (DR). We used regression models with Generalized Estimating Equations adjusted by age, sex, education, and within-family correlation to select features associated with cognitive status (normal cognition [NC] versus cognitive impairment [CI]; Bonferroni-corrected threshold p<0.001). Next, we developed a "polyfeature score" (PFS) for both immediate and delayed recall, each calculated as a weighted sum of the selected linguistic features. We then built a logistic regression model to evaluate the predictive value of each PFS for identifying cognitively impaired individuals. In secondary analyses, we used regression models as above to identify features associated with mild cognitive impairment subtype (amnestic [aMCI] versus nonamnestic [naMCI]; threshold p<.05). Results: The sample included 599 participants with NC and 110 with CI (mean age = 72.3 ± 11.0 years, 54% female). The regression identified 8 linguistic features for IR and 7 for DR that significantly predicted cognitive status. Decreased use of content words related to work (e.g., employed, school, police) and biological processes (e.g., cook, cafeteria, eat) and the use of negations (e.g., no, not, can't) were predictive of cognitive impairment in both recall conditions. In contrast, the use of other content word categories were predictive of cognitive status in only one recall condition (IR: leisure, cognitive processes, space; DR: drives, number). The use of fewer prepositions in IR, more first-person pronouns in DR, and fewer words in the past tense in DR were each associated with cognitive impairment. Word count was not predictive of cognitive status. Both PFSs were highly associated with cognitive status (PFS_IR ß= 0.74, p< 0.001; PFS_DR ß= 0.86, p= 0.001) with high discriminative value (PFS_IR AUC= 0.93, sensitivity = 0.81, specificity= 0.91; PFS_DR AUC= 0.95, sensitivity= 0.77, specificity= 0.88). In the CI subset, linguistic features differed between those classified as aMCI (n= 24) and naMCI (n= 40). Two function word categories predicted aMCI in IR whereas decreased word count, two function word categories, and two content word categories predicted aMCI in DR (all p<.05) Conclusions: Linguistic features from paragraph recall provide high predictive value for classifying cognitive status increasing its potential as a cognitive screener in clinical settings. Additionally, each recall condition identified unique linguistic features associated with cognitive impairment which may aid differentiation of cognitive impairment subtypes and elucidate processes underlying deficits in learning and recall. [ABSTRACT FROM AUTHOR]

Introduction: The Oblique Effect denotes superior performance for perceiving horizontal or vertical rather than diagonal or oblique stimuli. The current research investigated responding to oblique test stimuli in patients with mild cognitive impairment (MCI). Method: Four statistically-determined groups (n = 112) were studied; patients with little to no cognitive impairment (non-MCI, n = 39); subtle cognitive impairment (SCI, n = 15); amnestic MCI (aMCI, n = 28); and a combined mixed/dysexecutive MCI (mixed/dys MCI, n = 30). The ability to respond to oblique versus non-oblique test stimuli was assessed using the Judgment of Line Orientation Test (JOLO). Comprehensive neuropsychological assessment was also obtained. Between-group differences for JOLO oblique and non-oblique test stimuli were analyzed. Hierarchical linear regression models were constructed to identify relations between accuracy for oblique and non-oblique test items and neurocognitive domains. Results: The mixed/dys MCI group demonstrated lower accuracy for oblique test items compared to non-MCI patients. Accurate responding to oblique test items was associated with better performance on tests measuring executive control, processing speed, naming/lexical retrieval, and verbal concept formation. No between-group differences were seen for non-oblique items and these items were not associated with cognition. Conclusions:Significant impairment on oblique test items distinguished patients with multi-domain/dysexecutive MCI from non-MCI patients. Accurate responding to oblique test items was associated with a complex array of neuropsychological tests suggesting that multidimensional neuropsychological skills underlie the visuospatial reasoning abilities necessary for successful oblique line identification. Research associating responding to oblique versus non-oblique test stimuli using additional neuropsychological test paradigms, and MRI-defined neuroanatomical regions of interest may provide additional information about the brain-behavior relations that underlie MCI subtypes. [ABSTRACT FROM AUTHOR]

Objective: Previous research in mild cognitive impairment (MCI) suggests that visual episodic memory impairment may emerge before analogous verbal episodic memory impairment. The current study examined working memory (WM) test performance in MCI to assess whether patients present with greater visual versus verbal WM impairment. WM performance was also assessed in relation to hippocampal occupancy (HO), a ratio of hippocampal volume to ventricular dilation adjusted for demographic variables and intracranial volume. Methods: Jak et al. (2009) (The American Journal of Geriatric Psychiatry, 17 , 368–375) and Edmonds, Delano-Wood, Galasko, Salmon, & Bondi (2015) (Journal of Alzheimer's Disease , 47 (1), 231–242) criteria classify patients into four groups: little to no cognitive impairment (non-MCI); subtle cognitive impairment (SCI); amnestic MCI (aMCI); and a combined mixed/dysexecutive MCI (mixed/dys MCI). WM was assessed using co-normed Wechsler Adult Intelligence Scale-IV (WAIS-IV) Digit Span Backwards and Wechsler Memory Scale-IV (WMS-IV) Symbol Span Z -scores. Results: Between-group analyses found worse WMS-IV Symbol Span and WAIS-IV Digit Span Backwards performance for mixed/dys MCI compared to non-MCI patients. Within-group analyses found no differences for non-MCI patients; however, all other groups scored lower on WMS-IV Symbol Span than WAIS-IV Digit Span Backwards. Regression analysis with HO as the dependent variable was statistically significant for WMS-IV Symbol Span performance. WAIS-IV Digit Span Backwards performance failed to reach statistical significance. Conclusions: Worse WMS-IV Symbol Span performance was observed in patient groups with measurable neuropsychological impairment and better WMS-IV Symbol Span performance was associated with higher HO ratios. These results suggest that visual WM may be particularly sensitive to emergent illness compared to analogous verbal WM tests. [ABSTRACT FROM AUTHOR]

Background/Aims: Mild cognitive impairment (MCI) lacks a "gold standard" operational definition. The Jak/Bondi actuarial neuropsychological criteria for MCI are associated with improved diagnostic stability and prediction of progression to dementia compared to conventional MCI diagnostic approaches, although its utility in diagnosing MCI in old-old individuals (age 75+) is unknown. Therefore, we investigated the applicability of neuropsychological MCI criteria among old-old from the Framingham Heart Study. Methods: A total of 347 adults (ages 79–102) were classified as cognitively normal or MCI via Jak/Bondi and conventional Petersen/Winblad criteria, which differ on cutoffs for cognitive impairment and number of impaired scores required for a diagnosis. Cox models examined MCI status in predicting risk of progression to dementia. Results: MCI diagnosed by both the Jak/Bondi and Petersen/Winblad criteria was associated with incident dementia; however, when both criteria were included in the regression model together, only the Jak/Bondi criteria remained statistically significant. At follow-up, the Jak/Bondi criteria had a lower MCI-to-normal reversion rate than the Petersen/Winblad criteria. Conclusions: Our findings are consistent with previous research on the Jak/Bondi criteria and support the use of a comprehensive neuropsychological diagnostic approach for MCI among old-old individuals. [ABSTRACT FROM AUTHOR]

Clock Drawing Test performance was examined alongside other neuropsychological tests in mild cognitive impairment (MCI). We tested the hypothesis that clock-drawing errors are related to executive impairment. The current research examined 86 patients with MCI for whom, in prior research, cluster analysis was used to sort patients into dysexecutive (dMCI,n = 22), amnestic (aMCI,n = 13), and multidomain (mMCI,n = 51) subtypes. First, principal components analysis (PCA) and linear regression examined relations between clock-drawing errors and neuropsychological test performance independent of MCI subtype. Second, between-group differences were assessed with analysis of variance (ANOVA) where MCI subgroups were compared to normal controls (NC). PCA yielded a 3-group solution. Contrary to expectations, clock-drawing errors loaded with lower performance on naming/lexical retrieval, rather than with executive tests. Regression analyses found increasing clock-drawing errors to command were associated with worse performance only on naming/lexical retrieval tests. ANOVAs revealed no differences in clock-drawing errors between dMCI versus mMCI or aMCI versus NCs. Both the dMCI and mMCI groups generated more clock-drawing errors than the aMCI and NC groups in the command condition. In MCI, language-related skills contribute to clock-drawing impairment. [ABSTRACT FROM PUBLISHER]

Medial temporal lobe and temporoparietal brain regions are among the earliest neocortical sites to undergo pathophysiologic alterations in Alzheimer's disease (AD), although the underlying white matter changes in these regions is less well known. We employed diffusion tensor imaging to evaluate early alterations in regional white matter integrity in participants diagnosed with mild cognitive impairment (MCI). The following regions of interests (ROIs) were examined: 1) anterior cingulum (AC); 2) posterior cingulum (PC); 3) genu of the corpus callosum; 4) splenium of the corpus callosum; and 5) as a control site for comparison, posterior limb of the internal capsule. Forty nondemented participants were divided into demographically-similar groups based on cognitive status (MCI: n = 20; normal control: n = 20), and fractional anisotropy (FA) estimates of each ROI were obtained. MCI participants showed greater posterior white matter (i.e., PC, splenium) but not anterior white matter (i.e., AC, genu) changes, after adjusting for age, stroke risk, and whole brain volume. FA differences of the posterior white matter were best accounted for by changes in radial but not axial diffusivity. PC FA was also significantly positively correlated with hippocampal volume as well as with performance on tests of verbal memory, whereas stroke risk was significantly correlated with genu FA and was unrelated to PC FA. When investigating subtypes of our MCI population, amnestic MCI participants showed lower PC white matter integrity relative to those with non-amnestic MCI. Findings implicate involvement of posterior microstructural white matter degeneration in the development of MCI-related cognitive changes and suggest that reduced FA of the PC may be a candidate neuroimaging marker of AD risk. [ABSTRACT FROM AUTHOR]

Vascular dementia (VaD) is a heterogeneous term that has evolved to describe the behavioral syndromes associated with a variety of clinical and neuropathologic changes. As such, the VaD literature lacks a clear consensus regarding the neuropsychological and other constituent characteristics associated with various cerebrovascular changes. We address the issues articulated by Paul and colleagues (Paul, Garrett,&Cohen, 2003), by offering four recommendations to refine the clinical assessment and diagnostic decision-making process of individuals with suspected cerebrovascular changes: (a) Describing the nature of vascular changes may facilitate predictions regarding the neuropsychological profile of subtypes of VaD; (b) employ a process approach to assessment, measuring cognitive constructs in addition to test scores to describe the neuropsychological profiles of types of VaD; (c) integrate direct MRI observations of the brain and other collateral data in the diagnostic process; and (d) consider using"vascular cognitive impairment, no dementia"for suspected prodromal VaD. [ABSTRACT FROM AUTHOR]

The article discusses the science of vascular cognitive impairment (VCI) which receives a little attention in medicine due to sociopolitical issues. It states that researcher named V. Hachinski and colleagues spearheaded the investigation to explain the connection of vascular diseases, brain health and cognition. It mentions that Hachinski discovered the Triple T Approach that helps understand and characterize VCI.

There are few cognitive screening tools appropriate for fast-paced settings with limited staffing, and particularly in preoperative evaluation clinics. The Society for Perioperative Assessment and Quality Improvement (SPAQI) convened experts in neuropsychology, geriatric medicine, and anesthesiology to conduct a review of the literature and compile a comprehensive list of cognitive screening tools used within primary care and preoperative settings. This Recommendations Statement: 1. summarizes a review of the literature on existing cognitive screening tools used within preoperative settings; 2. discusses factors to consider when selecting cognitive screening tools in a preoperative environment; and 3. includes a work flow diagram to guide use of these screening measures. Methodology involved searching peer-reviewed literature for 29 cognitive screening tools which were identified from the literature that fit inclusion criteria. Of these 29, seven tests have been used in preoperative settings and are discussed. These seven had an average administration time ranging from one to ten minutes. Memory, language, and attention were the most commonly evaluated cognitive domains. Most had adequate sensitivity and specificity to detect cognitive impairment/dementia. While information on the psychometric properties of these tools is limited, the tools discussed are appropriate for lay examiners, are short in duration, and accessible for free or at a low cost. We describe factors that must be considered prior to instrument selection. • Utilize cognitive screeners that are accessible, brief, easy to administer, and evaluate multiple domains • Avoid utilizing cognitive screening instruments that have no documented use within preoperative settings • Use administration and scoring instructions included with the screener to train staff • Incorporate caregiver rating and functional status examinations • Establishing level of independence may assist in determining if a referral to neurology or neuropsychology is warranted [ABSTRACT FROM AUTHOR]