Longitudinal deficits to attention, executive, and working memory in subtypes of mild cognitive impairment.

Objective: Mild cognitive impairment (MCI) has emerged as a classification for a prodromal phase of cognitive decline that may precede the emergence of Alzheimer's disease (AD). Recent research suggests that attention, executive, and working memory deficits may appear much earlier in the progression of AD than traditionally conceptualized, and may be more consistently associated with the later development of AD than memory processing deficits. The present study longitudinally tracked attention, executive and working memory functions in subtypes of MCI. Method: In a longitudinal study, 52 amnestic MCI (a-MCI), 29 nonamnestic MCI (na-MCI), and 25 age- and education-matched controls undertook neuropsychological assessment of visual and verbal memory, attentional processing, executive functioning, working memory capacity, and semantic language at 10 month intervals. Results: Analysis by repeated measures ANOVA indicate that the a-MCI and na-MCI groups displayed a decline in simple sustained attention (ηp2 = .054) with a significant decline on a task of divided attention (ηp2 = .053) being evident in the a-MCI group. Stable deficits were found on other measures of attention, working memory and executive function in the a-MCI and na-MCI groups. The a-MCI group displayed stable impairments to visual and verbal memory. Conclusions: The results indicate that a-MCI and na-MCI display a stable pattern of deficits to attention, working memory, and executive function. The decline in simple sustained attention in a-MCI and n-MCI groups and to divided attention in a-MCI may be early indicators of possible transition to dementia from MCI. However, further research is required to determine this. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Longitudinal change in cognitive performance among individuals with mild cognitive impairment.

The authors used mixed-effects growth models to examine longitudinal change in neuropsychological performance over a 4-year period among 197 individuals who were either normal or had mild cognitive impairment (MCI) at baseline. At follow-up, the participants were divided into 4 groups: (a) controls: participants who were normal at both baseline and follow-up (n = 33), (b) stables: participants with MCI whose Clinical Dementia Rating-Sum of Boxes (CDR-SB) score did not differ between the first and last evaluations (n = 22), (c) decliners: participants with MCI whose CDR-SB score declined between the first and last evaluations (n = 95), and (d) converters: participants who received a clinical diagnosis of Alzheimer's disease during the follow-up period (n = 47). Only the Episodic Memory factor showed a significantly greater rate of decline over the follow-up period among the converters. Two other factors were significantly lower in converters at baseline in comparison with other groups (the executive function factor and the general knowledge factor), but the rate of decline over time did not differ. Individuals with an APOE ε4 allele scored lower on the episodic memory and executive function factors at baseline. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive estimation impairment in Alzheimer disease and mild cognitive impairment.

Intact executive functioning is believed to be required for performance on tasks requiring cognitive estimations. This study used a revised version of a cognitive estimations test (CET) to investigate whether patients with Alzheimer's disease (AD) and mild cognitive impairment (MCI) were impaired on the CET compared with normal elderly controls (NECs). Neuropsychological tests were administered to determine the relationship between CET performance and other cognitive domains. AD patients displayed impaired CET performance when compared with NECs but MCI patients did not. Negative correlations between tests of working memory (WM) and semantic memory and the CET were found in NECs and AD patients, indicating that these cognitive domains were important for CET performance. Regression analysis suggests that AD patients were unable to maintain semantic information in WM to perform the task. The authors conclude that AD patients display deficits in working memory, semantic memory, and executive function, which are required for adequate CET performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

The effect of education on the onset and rate of terminal decline.

Differences in the time of onset and magnitude of terminal decline were examined in three cognitive domains: processing speed, episodic memory, and global function. In addition, cognitive reserve was investigated by testing whether education affected the onset or rate of decline across these domains. Eight hundred ninety-six community-dwelling Australian adults aged ≥ 70 years were assessed up to four times over 12 years, with vital status followed for 17 years. For each of the cognitive measures, a series of change point models were fitted across the 20 years before death to find the optimal point at which terminal decline was distinguished from preterminal decline. Change points were then assessed separately for high- and low-education groups. The change points were 8.5 years for processing speed (95% CI: 6.0–11.2 years), 7.1 years for global function (6.2–9.3), and 6.6 years for episodic memory (5.3–7.1). The rate of decline was two to four times greater in the terminal phase relative to the preterminal phase, depending on the domain. Increased education changed the terminal decline effect differently for each of the three tests, either by significantly hastening the onset of terminal decline and decreasing the rate of decline, or by increasing the rate of either preterminal or terminal decline. Analyses were repeated excluding participants diagnosed with dementia, with no substantive change to the outcomes. In conclusion, the rate and onset of terminal decline varied somewhat across cognitive domains. Education affected terminal decline differently across the domains, but this modification was not consistent with the predictions of cognitive reserve theory. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Cognitive profiles of mild cognitive impairment with and without vascular disease.

This study examined whether the cognitive profile of subjects with mild cognitive impairment (MCI) with vascular disease differs from that of MCI subjects with no vascular disease. Consecutive MCI subjects with vascular disease (n=60) and matched MCI subjects with no vascular disease (n=60) were included in the study and were compared with healthy control subjects (n=60). The neuropsychological assessment comprised tests of speed and attention, episodic memory, visuospatial function, language, and executive function. Control subjects performed significantly better than did both MCI groups on the neuropsychological battery. MCI subjects with no vascular disease performed better overall than did MCI subjects with vascular disease, most clearly on tests of speed and attention, visuospatial function, and executive function. MCI subjects with and without vascular disease exhibited differences, both in terms of overall performance and of cognitive profiles. These differences can be largely explained by deficits in speed and attention and in executive function of the MCI subjects with vascular disease. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Longitudinal MRI and cognitive change in healthy elderly.

Cross-sectional studies of normal aging indicate an association between memory and hippocampal volume, and between executive functioning and subcortical-frontal circuits. Much less is known, however, about the relationship between longitudinal MRI changes and cognitive decline. The authors hypothesized that longitudinal change in memory would be best predicted by change in hippocampal volumes, whereas change in executive functioning would be best predicted by cortical atrophy and progression of MRI markers of cerebrovascular disease. For this study, 50 healthy elderly subjects underwent structural MRI and cognitive testing at baseline and again at follow-up, with a mean follow-up interval of 45 months. Volumetric MRI measures were hippocampus, cortical gray matter, white matter signal hyperintensity (WMSH), and lacunae. Neuropsychological measures were psychometrically robust composite scores of episodic memory (MEM) and executive functioning (EXEC). Hierarchical multiple regression indicated that a decrease in hippocampus was associated with a decline in MEM, whereas decreased cortical gray matter and increased WMSH were independently associated with a decline in EXEC. Results suggest that in normal aging, cognitive functioning declines as cortical gray matter and hippocampus decrease, and WMSH increases. The association between WMSH and EXEC further highlights the cognitive sequealae associated with cerebrovascular disease in normal elderly. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Deficient Strategic Control of Verbal Encoding and Retrieval in Individuals With Methamphetamine Dependence.

Methamphetamine (MA) dependence is associated with deficits in episodic verbal memory, but the cognitive mechanisms underlying such impairments are not known. The authors evaluated a component process model of episodic verbal memory in 87 persons with MA dependence (MA+) and 71 demographically similar non-MA-using controls (MA-). Compared with MA- controls, MA+ participants demonstrated deficient overall learning, free recall, and utilization of semantic clustering, as well as higher rates of repetitions and intrusions. No between-groups differences were evident on measures of serial clustering, retention, or recognition discrimination. Taken together, these findings indicate that MA dependence is associated with deficient strategic (i.e., executive) control of verbal encoding and retrieval, which is consistent with the sequelae of MA-related prefronto-striatal circuit neurotoxicity. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Is the apolipoprotein e genotype a biomarker for mild cognitive impairment? Findings from a nationally representative study.

Objective: Although the ε4 allele of the apolipoprotein E (APOE) genotype is a known risk factor for Alzheimer's dementia (AD), prior findings on whether it is also a risk factor for mild cognitive impairment (MCI) have been inconsistent. We tested two contrasting explanations: (a) an ε4-AD specificity hypothesis, and (b) a measurement insensitivity hypothesis. Method: The frequency of the ε4 allele was investigated in older adults (mean age > 70) with various types of cognitive impairment (including MCI) and various types of dementia (including AD) with the aging, demographics, and memory study (ADAMS) of the National Institute on Aging's Health and Retirement Study (HRS). The ADAMS controls sources of Type I and Type II error that are posited in the ε4-AD specificity hypothesis and the measurement insensitivity hypothesis, and it is the only nationally representative data set on aging and cognitive impairment. Results: ε4 was a reliable predictor of MCI, with a frequency of 32% in MCI subjects versus 20% in healthy control subjects. This link was specific to MCI because ε4 was not a risk factor for other forms of cognitive impairment without dementia. Conclusions: The results support the measurement insensitivity hypothesis rather than the ε4-AD specificity hypothesis and are consistent with recent research showing modest reductions in cognitive performance among normal functioning ε4 carriers. (PsycINFO Database Record (c) 2011 APA, all rights reserved)     

Selectivity of executive function deficits in mild cognitive impairment.

Impairment in executive cognition (EC) is now recognized as relatively common among older persons with mild cognitive impairment (MCI) and may be predictive of the development of dementia. However, both MCI and executive functioning are broad and heterogeneous constructs. The present study sought to determine whether impairments in specific domains of EC are associated with specific subtypes of MCI. MCI patients (n = 124) were divided into 4 subgroups (amnestic vs. nonamnestic, and single- vs. multiple-domain) on the basis of their performance of widely used neuropsychological screening tests. These patients and 68 normal older persons were administered 18 clinical and experimental tests of executive function. Principal components analysis suggested 2 highly reliable EC components, planning/problem solving and working memory, and a less reliable 3rd component, judgment. Planning/problem solving and working memory, but not judgment, were impaired among the MCI patients. This was true even among those with “pure amnestic” MCI, the least impaired group overall. Multiple-domain MCI patients had more severe impairments in planning/problem solving and working memory than single-domain patients, leading to the supposition that they, not pure amnestic MCIs, are at highest risk of imminent dementia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive ability at age 11 and 70 years, information processing speed, and APOE variation: The Lothian Birth Cohort 1936 study.

The e4 allele of the apolipoprotein E (APOE) gene confers risk of Alzheimer's disease and, in some studies, relates to cognitive ability and decline in older people without Alzheimer's disease. Its relationship with processing speed, a contributor to cognitive decline with age, is largely unknown. This study tests the association of APOE with cognition and speed, with and without covarying childhood mental ability. The 1,013 participants were tested on cognitive ability at age 11 as part of the Scottish Mental Survey of 1947 and, at age 70, were tested on reasoning, working memory, information processing speed, and executive function. The results showed that APOE was associated with the general cognitive factor, 2 nonverbal tests, and choice reaction time (RT) variability; as expected, the e4 allele was the risk allele. RT measures and a general speed factor were nonlinearly related to APOE when factoring childhood ability (p     

Comparison of neuropsychological functioning in Alzheimer's disease and frontotemporal dementia

Neuropsychological changes distinguishing mild Alzheimer's disease (AD) from frontotemporal dementia (FTD) have been described, but empirical verification of differential cognitive characteristics is lacking. Archival neuropsychological data on 15 FTD patients, 16 AD patients, and 16 controls were compared. Controls outperformed both patient groups on measures of verbal and nonverbal memory, executive ability, and constructional skill, with AD patients showing more widespread memory decline. No differences were found between the 3 groups in confrontation naming, recognition memory, or basic attention. Patient groups differed only in nonverbal memory, with FTD patients performing significantly better than AD patients. However, patient groups also differed in pattern of performance across executive and memory domains. Specifically, AD patients exhibited significantly greater impairment on memory than executive tasks, whereas the opposite pattern characterized the FTD group. These findings suggest that examination of relative rankings of scores across cognitive domains, in addition to interpretation of individual neuropsychological scores, may be useful in differential diagnosis of FTD versus AD.     

Semantic inhibition impairment in mild cognitive impairment: A distinctive feature of upcoming cognitive decline?

This study aimed to measure semantic inhibitory capacities in persons with a diagnosis of Alzheimer’s disease (AD) or mild cognitive impairment (MCI), in healthy older and younger adults. This was done by relying on a computerized adaptation of the Hayling task, designed to diminish the likelihood of using alternative noninhibitory strategies. Participants with both AD and MCI showed impaired performance on the inhibition condition. Participants with AD showed both poorer score and an increased number of errors, whereas persons with MCI obtained lower score. There was also an effect of normal aging in the inhibition condition when considering reaction time only. In participants with MCI and AD, there was a significant correlation between lexico-semantic capacities and performance on the automatic condition. Follow-up analysis revealed that participants with MCI who experienced a subsequent significant cognitive decline had impaired performance in the inhibition condition at the time of the experiment, while participants with MCI who remained stable did not. Overall, results indicate that semantic inhibition of a prepotent response is impaired in participants with MCI and may have predictive value regarding future decline, supporting its prognostic role in the early identification of dementia. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Impact of age on long-term cognitive function after traumatic brain injury.

Objective: To examine the association of age and time postinjury with cognitive outcome 5–22 years following traumatic brain injury (TBI), in relation to matched uninjured controls. Methods: One hundred twelve participants with mild to very severe TBI, aged 16–81 years at the time of injury, were cognitively assessed on measures of processing speed and attention, verbal and visual memory, executive function, and working memory. Results were compared with those of 112 healthy controls individually matched for current age, gender, education, and estimated IQ. Results: Older injured individuals performed worse than did younger injured individuals across all cognitive domains, after controlling for the performance of controls. In relation to matched controls, long-time survivors performed disproportionately worse than did more recently injured individuals, irrespective of age. Conclusions: After maximum spontaneous recovery from TBI, poorer cognitive functioning appears to be associated with both older age at the time of injury and increased time postinjury. These findings have implications for prognosis, early treatment recommendations, and long-term issues of differential diagnosis and management planning. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive decline from estimated premorbid status predicts neurodegeneration in Alzheimer's disease.

This study investigated the relationship between premorbid and current cognitive function with respect to the clinical features of patients with various types of neurodegeneration in the form of Alzheimer's disease (AD), mild cognitive impairment (MCI), and subjective cognitive impairment (SCI), as compared with a healthy control group (C). Clinical features (MMSE, cognitive and depressive symptoms), genetics (apolipoprotein E; APOE) and measures of neurodegeneration (Aβ42, t-tau, and p-tau) were examined, as well as present cognitive function. Various methods of assessing premorbid cognitive function were compared, including a Swedish NART-analogous test (Irregularly Spelled Words; ISW), a Swedish lexical decision test (SLDT), a Hold test (Information in WAIS-R), Best current performance test, and combined demographic characteristics. Results showed that cognitive decline (premorbid minus current cognitive function) based on SLDT and ISW was a significant predictor for MMSE and Aβ42, whereas corresponding associations for present cognitive function and decline measures based on other methods were less powerful. Results also showed that specific verbal abilities (e.g., SLDT and ISW) were insensitive to AD and that these abilities indicated premorbid cognitive function in retrospect. In conclusion, cognitive decline from premorbid status reflects the disease processes. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive impairment in preclinical Alzheimer's disease: A meta-analysis.

To determine the size of the impairment across different cognitive domains in preclinical Alzheimer's disease (AD), a meta-analysis based on 47 studies involving 9,097 controls and 1,207 preclinical AD cases was conducted. There were marked preclinical deficits in global cognitive ability, episodic memory, perceptual speed, and executive functioning; somewhat smaller deficits in verbal ability, visuospatial skill, and attention; and no preclinical impairment in primary memory. Younger age (     

Robust and conventional neuropsychological norms: Diagnosis and prediction of age-related cognitive decline.

The aim of the study was to compare the performance of Robust and Conventional neuropsychological norms in predicting clinical decline among healthy adults and in mild cognitive impairment (MCI). The authors developed Robust baseline cross sectional and longitudinal change norms from 113 healthy participants retaining a normal diagnosis for at least 4 years. Baseline Conventional norms were separately created for 256 similar healthy participants without follow-up. Conventional and Robust norms were tested in an independent cohort of longitudinally studied healthy (n=223), MCI (n=136), and Alzheimer's disease (AD, n=162) participants; 84 healthy participants declined to MCI or AD (NL→DEC), and 44 MCI declined to AD (MCI→AD). Compared to Conventional norms, baseline Robust norms correctly identified a higher proportion of NL→DEC with impairment in delayed memory and attention-language domains. Both norms predicted decline from MCI→AD. Change norms for delayed memory and attention-language significantly incremented baseline classification accuracies. These findings indicate that Robust norms improve identification of healthy individuals who will decline and may be useful for selecting at-risk participants for research studies and early interventions. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Three-year changes in cognitive performance as a function of apolipoprotein E genotype: Evidence from very old adults without dementia.

This study examined whether baseline cognitive performance and 3-year longitudinal changes were influenced by apolipoprotein E ε4 (APOE-ε4) allele. Participants consisted of 20 APOE-ε4 (2 ε2/ε4; 17 ε3/ε4; 1 ε4/ε4) and 54 non-ε4 (12 ε2/ε3; 42 ε3/ε3) very old adults without dementia (M?=?81.82?±?5.06 years) participating in a population-based longitudinal study. Cognitive performance was indexed by the Mini-Mental State Examination and multiple indexes of memory, visuospatial, and verbal performance. The results indicated no significant baseline differences between the 2 APOE groups in any cognitive performance measure. However, analyses revealed that the APOE-ε4 group experienced greater negative change in recognition memory for faces and words. Changes in tasks assessing other abilities did not vary as a function of APOE status. The authors concluded that APOE-ε4 status may not influence cognitive performance in adults without dementia and speculated that when such effects do occur (e.g., decline in recognition memory), these may be related to impending dementia, rather than to the influence of the specific genotype on cognition in normal aging. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Cognitive predictors of medical decision-making capacity in traumatic brain injury.

Objective: To identify cognitive predictors of medical decision-making capacity (MDC) in participants with moderate to severe traumatic brain injury (TBI). Participants: At baseline, participants were 34 adults with TBI and 20 healthy adults. At 6-month follow-up, participants were 24 adults with TBI and 20 healthy adults. Main Outcome Measures: Participants were administered the Capacity to Consent to Treatment Instrument (CCTI) and neuropsychological test measures. Multivariate cognitive predictor models were developed for CCTI consent abilities/standards (S) of understanding (S5); reasoning (S4); and appreciation (S3). Results: At baseline, short-term verbal memory and semantic fluency predicted TBI group performance on understanding (S5); short-term verbal memory and attention predicted performance on reasoning (S4); and working memory predicted performance on appreciation (S3). At 6 month follow-up, executive function, verbal processing speed, and working memory predicted TBI performance on understanding (S5); working memory and short-term memory predicted reasoning (S4); and basic executive functioning predicted appreciation (S3). Conclusions: Multiple cognitive functions are associated with acute impairment and partial recovery of MDC in patients with TBI. Short-term verbal memory predicted consent capacity of TBI participants at the time of acute inpatient hospitalization, while executive functioning and working memory predicted improved capacity at six-month follow-up. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Long-Term Memory Deficits in Schizophrenia: Primary or Secondary Dysfunction?

Long-term memory impairment is often found in schizophrenia. The question remains whether this is caused by other cognitive deficits. One hundred eighteen first-episode patients were compared with 45 control participants on several memory tasks. The role of processing speed and central executive functions on memory performance was examined with regression analysis for all participants and for patients separately. Deficits were found in general verbal learning performance and retrieval in episodic memory and semantic memory. Processing speed reduced disease-related variance in all memory variables. Coordination, organization of information, and speed of processing were the best predictors for long-term memory deficits in patients. The amount of explained variance, however, is small, especially in general verbal learning performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)     

Apolipoprotein E and Cognitive Performance: A Meta-Analysis.

The ε4 allele of the apolipoprotein E (APOE) gene is a known risk factor for Alzheimer's disease and may also affect cognitive performance in normal aging. Evidence of the presence and magnitude of ε4-related cognitive deficits was examined with a meta-analysis of the available literature. Thirty-eight studies were included, and cognitive performance was collapsed into 8 domains. Results indicated significant APOE-ε4 group differences for global cognitive functioning, episodic memory, and executive functioning, in favor of non-ε4 carriers. In addition, older age and APOE-ε4 heterozygosity was associated with smaller ε4-related impairments. The meta-analysis results suggest that APOE-ε4 genotype does affect cognitive performance in healthy aging, although the influence is relatively small and specific to certain domains of cognitive performance. (PsycINFO Database Record (c) 2010 APA, all rights reserved)