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1.  Cognitive correlates of HVOT performance differ between individuals with mild cognitive impairment and normal controls 
To clinically characterize performance on the Hooper Visual Organization Test (HVOT) among participants with mild cognitive impairment (MCI) and to identify naming and executive functioning correlates associated with HVOT performance among MCI participants and normal controls (NC).
The HVOT is a common neuropsychological instrument that measures visuospatial skills and agnosia. It has, however, been criticized for its multifactorial nature, as several studies have reported executive or language correlates of HVOT performance. To our knowledge, simultaneous comparison of executive functioning and language demands of the HVOT has never been performed among an older cohort.
The HVOT, two tests of executive functioning [Trail Making Test, Part B (TMT-B), Controlled Oral Word Association (COWA)] and two tests of naming [abbreviated Boston Naming Test (BNT), Animal Naming] were administered to 222 NC, 166 MCI, and 68 Alzheimer’s disease (AD) individuals.
HVOT scores were significantly different between all three groups in the expected direction (AD < MCI < NC). Linear regression among NC participants revealed that COWA, age, and BNT were significantly associated with HVOT scores, accounting for 12%, 6%, and 4% of HVOT variance, respectively. Among MCI participants, the BNT accounted for 43% of HVOT variance. Neither TMT-B nor Animal Naming was a significant predictor for either group.
Among NC participants, rapid word generation (i.e., COWA), a measure of executive functioning, is the most salient predictor of HVOT performance. In contrast, lexical retrieval (i.e., BNT) is the most salient language or executive functioning predictor of HVOT performance among MCI participants. These findings extend previous claims that the HVOT is multifactorial by suggesting that reduced HVOT performance in MCI patients may be related to mild lexical retrieval impairments.
PMCID: PMC2746420  PMID: 16893623
Object recognition; Mild cognitive impairment; Hooper Visual Organization Test
2.  Computerized Cognitive Training in Cognitively Healthy Older Adults: A Systematic Review and Meta-Analysis of Effect Modifiers 
PLoS Medicine  2014;11(11):e1001756.
Michael Valenzuela and colleagues systematically review and meta-analyze the evidence that computerized cognitive training improves cognitive skills in older adults with normal cognition.
Please see later in the article for the Editors' Summary
New effective interventions to attenuate age-related cognitive decline are a global priority. Computerized cognitive training (CCT) is believed to be safe and can be inexpensive, but neither its efficacy in enhancing cognitive performance in healthy older adults nor the impact of design factors on such efficacy has been systematically analyzed. Our aim therefore was to quantitatively assess whether CCT programs can enhance cognition in healthy older adults, discriminate responsive from nonresponsive cognitive domains, and identify the most salient design factors.
Methods and Findings
We systematically searched Medline, Embase, and PsycINFO for relevant studies from the databases' inception to 9 July 2014. Eligible studies were randomized controlled trials investigating the effects of ≥4 h of CCT on performance in neuropsychological tests in older adults without dementia or other cognitive impairment. Fifty-two studies encompassing 4,885 participants were eligible. Intervention designs varied considerably, but after removal of one outlier, heterogeneity across studies was small (I2 = 29.92%). There was no systematic evidence of publication bias. The overall effect size (Hedges' g, random effects model) for CCT versus control was small and statistically significant, g = 0.22 (95% CI 0.15 to 0.29). Small to moderate effect sizes were found for nonverbal memory, g = 0.24 (95% CI 0.09 to 0.38); verbal memory, g = 0.08 (95% CI 0.01 to 0.15); working memory (WM), g = 0.22 (95% CI 0.09 to 0.35); processing speed, g = 0.31 (95% CI 0.11 to 0.50); and visuospatial skills, g = 0.30 (95% CI 0.07 to 0.54). No significant effects were found for executive functions and attention. Moderator analyses revealed that home-based administration was ineffective compared to group-based training, and that more than three training sessions per week was ineffective versus three or fewer. There was no evidence for the effectiveness of WM training, and only weak evidence for sessions less than 30 min. These results are limited to healthy older adults, and do not address the durability of training effects.
CCT is modestly effective at improving cognitive performance in healthy older adults, but efficacy varies across cognitive domains and is largely determined by design choices. Unsupervised at-home training and training more than three times per week are specifically ineffective. Further research is required to enhance efficacy of the intervention.
Please see later in the article for the Editors' Summary
Editors' Summary
As we get older, we notice many bodily changes. Our hair goes grey, we develop new aches and pains, and getting out of bed in the morning takes longer than it did when we were young. Our brain may also show signs of aging. It may take us longer to learn new information, we may lose our keys more frequently, and we may forget people's names. Cognitive decline—developing worsened thinking, language, memory, understanding, and judgment—can be a normal part of aging, but it can also be an early sign of dementia, a group of brain disorders characterized by a severe, irreversible decline in cognitive functions. We know that age-related physical decline can be attenuated by keeping physically active; similarly, engaging in activities that stimulate the brain throughout life is thought to enhance cognition in later life and reduce the risk of age-related cognitive decline and dementia. Thus, having an active social life and doing challenging activities that stimulate both the brain and the body may help to stave off cognitive decline.
Why Was This Study Done?
“Brain training” may be another way of keeping mentally fit. The sale of computerized cognitive training (CCT) packages, which provide standardized, cognitively challenging tasks designed to “exercise” various cognitive functions, is a lucrative and expanding business. But does CCT work? Given the rising global incidence of dementia, effective interventions that attenuate age-related cognitive decline are urgently needed. However, the impact of CCT on cognitive performance in older adults is unclear, and little is known about what makes a good CCT package. In this systematic review and meta-analysis, the researchers assess whether CCT programs improve cognitive test performance in cognitively healthy older adults and identify the aspects of cognition (cognitive domains) that are responsive to CCT, and the CCT design features that are most important in improving cognitive performance. A systematic review uses pre-defined criteria to identify all the research on a given topic; meta-analysis uses statistical methods to combine the results of several studies.
What Did the Researchers Do and Find?
The researchers identified 51 trials that investigated the effects of more than four hours of CCT on nearly 5,000 cognitively healthy older adults by measuring several cognitive functions before and after CCT. Meta-analysis of these studies indicated that the overall effect size for CCT (compared to control individuals who did not participate in CCT) was small but statistically significant. An effect size quantifies the difference between two groups; a statistically significant result is a result that is unlikely to have occurred by chance. So, the meta-analysis suggests that CCT slightly increased overall cognitive function. Notably, CCT also had small to moderate significant effects on individual cognitive functions. For example, some CCT slightly improved nonverbal memory (the ability to remember visual images) and working memory (the ability to remember recent events; short-term memory). However, CCT had no significant effect on executive functions (cognitive processes involved in planning and judgment) or attention (selective concentration on one aspect of the environment). The design of CCT used in the different studies varied considerably, and “moderator” analyses revealed that home-based CCT was not effective, whereas center-based CCT was effective, and that training sessions undertaken more than three times a week were not effective. There was also some weak evidence suggesting that CCT sessions lasting less than 30 minutes may be ineffective. Finally, there was no evidence for the effectiveness of working memory training by itself (for example, programs that ask individuals to recall series of letters).
What Do These Findings Mean?
These findings suggest that CCT produces small improvements in cognitive performance in cognitively healthy older adults but that the efficacy of CCT varies across cognitive domains and is largely determined by design aspects of CCT. The most important result was that “do-it-yourself” CCT at home did not produce improvements. Rather, the small improvements seen were in individuals supervised by a trainer in a center and undergoing sessions 1–3 times a week. Because only cognitively healthy older adults were enrolled in the studies considered in this systematic review and meta-analysis, these findings do not necessarily apply to cognitively impaired individuals. Moreover, because all the included studies measured cognitive function immediately after CCT, these findings provide no information about the durability of the effects of CCT or about how the effects of CCT on cognitive function translate into real-life outcomes for individuals such as independence and the long-term risk of dementia. The researchers call, therefore, for additional research into CCT, an intervention that might help to attenuate age-related cognitive decline and improve the quality of life for older individuals.
Additional Information
Please access these websites via the online version of this summary at
This study is further discussed in a PLOS Medicine Perspective by Druin Burch
The US National Institute on Aging provides information for patients and carers about age-related forgetfulness, about memory and cognitive health, and about dementia (in English and Spanish)
The UK National Health Service Choices website also provides information about dementia and about memory loss
MedlinePlus provides links to additional resources about memory, mild cognitive impairment, and dementia (in English and Spanish)
PMCID: PMC4236015  PMID: 25405755
3.  Geriatric Performance on an Abbreviated Version of the Boston Naming Test 
Applied neuropsychology  2007;14(3):215-223.
Abbreviated neuropsychological protocols are increasingly utilized secondary to time-constraints within research and healthcare settings, yet normative data for these abbreviated instruments are lacking. We present geriatric performances and normative data for the Boston Naming Test 30-item even verion (BNT-30). Data were utilized from the BU-ADCC registry (n = 441, ages 55-98) and included 219 normal controls (NC), 155 participants with mild cognitive impairment (MCI), and 67 participants with Alzheimer’s disease (AD). The NC group (M = 28.7, SD = 1.8) significantly outperformed both MCI (M = 26.2, SD = 4.4) and AD (M = 22.1, SD = 4.8) groups, and the MCI group outperformed the AD group. Normative data generated for the NC participants revealed a significant between-group difference for sex (males M = 29.1, SD = 1.7; females M = 28.4, SD = 1.8) and race (White M = 28.8, SD = 1.7; African American M = 27.5, SD = 2.1). The racial disparity remained even after adjusting for education level (p = .002) and literacy (p < .001). ANOVAs for the NC group were non-significant for age but significant for education level (p = .001). Geriatric normative data therefore suggest that sex, race, and education are all associated with naming performance, and these variables should be taken into consideration when interpreting geriatric BNT-30 performance.
PMCID: PMC2741691  PMID: 17848132
Alzheimer’s disease; Boston Naming Test; geriatrics; language; lexical retrieval; mild cognitive impairment; neuropsychological measures; normative data
4.  Culture Qualitatively but Not Quantitatively Influences Performance in the Boston Naming Test in a Chinese-Speaking Population 
The Boston Naming Test (BNT) is the most frequently administered confrontational naming test, but the cultural background of the patients may influence their performance in the BNT. The aim of this study was to identify differences in performance in the BNT between a Chinese population in Taiwan, Chinese populations in other areas and a Caucasian population.
A total of 264 native, Chinese-speaking, cognitively normal elders aged >60 years were enrolled in our study and conducted the 30-item Chinese version of the BNT. Another 10 BNT studies were categorized, analyzed and compared with the present study.
Higher education was associated with higher scores, whereas age and gender had no effect on performance in the BNT. The score of the Chinese-speaking population was equivalent to the English-speaking population. A disparity in difficulties with items was not only apparent between the Taiwanese and Caucasian populations, but also between the Chinese-speaking populations in the different geographic areas.
For the most part, the impact of culture on performance in the BNT may not be quantitative but qualitative. Attention should be paid to a potential effect of culture on difficulties with items when administering the BNT to non-English-speaking populations. Understanding differences in performance in the BNT in distinct cultural settings improves the clinical application of the BNT.
PMCID: PMC4024970  PMID: 24847347
Boston Naming Test; Chinese-speaking population; Cross-cultural comparison; Elderly; Taiwan

5.  Dementia in Fragile X-Associated Tremor/Ataxia Syndrome (FXTAS): Comparison with Alzheimer’s Disease 
Neurocognitive deficits in fragile X-associated tremor/ataxia syndrome (FXTAS) involve attentional control, working memory, executive functioning, and declarative and procedural learning. To date, no studies comparing FXTAS with other dementias have been done. We characterize the dementia in FXTAS, comparing it with Alzheimer’s disease.
Retrospective chart review of 68 adults (50 men, 18 women) with FXTAS. 20 men with FXTAS dementia were matched by age, gender, and education to patients with mild Alzheimer's dementia (AD). Neuropsychological measures were compared between the two groups: Boston Naming Test (BNT), phonemic fluency (Controlled Oral Word Association Test), digit span forward (DSF) and backward (DSB). Comparisons were based on analysis of covariance and t-tests to assess significant differences between groups with respect to the neuropsychological measures.
50% of men with FXTAS and no women were cognitively impaired. On mean scores of verbal fluency (22.83 in FXTAS vs. 28.83 in AD, p = 0.112), working memory (DSB, 4.80 in AD vs. 5.41 in FXTAS, p = 0.359), and language (BNT, 48.54 in AD vs. 54.20 in FXTAS, p = 0.089), there were no significant differences. Digit span forward, measuring attention, was significantly higher in subjects with FXTAS dementia (8.59, vs. 7.10 in AD, p = 0.010).
Individuals with FXTAS have significant cognitive deficits, on the order of those in AD although the cognitive profiles in these dementias are not similar. Further research is needed to outline the neuropsychiatric profile in FXTAS and the correlation of genetic markers with the progression and severity of cognitive loss.
PMCID: PMC2898561  PMID: 18384046
6.  Prevalence, Distribution, and Impact of Mild Cognitive Impairment in Latin America, China, and India: A 10/66 Population-Based Study 
PLoS Medicine  2012;9(2):e1001170.
A set of cross-sectional surveys carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India reveal the prevalence and between-country variation in mild cognitive impairment at a population level.
Rapid demographic ageing is a growing public health issue in many low- and middle-income countries (LAMICs). Mild cognitive impairment (MCI) is a construct frequently used to define groups of people who may be at risk of developing dementia, crucial for targeting preventative interventions. However, little is known about the prevalence or impact of MCI in LAMIC settings.
Methods and Findings
Data were analysed from cross-sectional surveys established by the 10/66 Dementia Research Group and carried out in Cuba, Dominican Republic, Peru, Mexico, Venezuela, Puerto Rico, China, and India on 15,376 individuals aged 65+ without dementia. Standardised assessments of mental and physical health, and cognitive function were carried out including informant interviews. An algorithm was developed to define Mayo Clinic amnestic MCI (aMCI). Disability (12-item World Health Organization disability assessment schedule [WHODAS]) and informant-reported neuropsychiatric symptoms (neuropsychiatric inventory [NPI-Q]) were measured. After adjustment, aMCI was associated with disability, anxiety, apathy, and irritability (but not depression); between-country heterogeneity in these associations was only significant for disability. The crude prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Country differences changed little (range 0.6%–4.6%) after standardization for age, gender, and education level. In pooled estimates, aMCI was modestly associated with male gender and fewer assets but was not associated with age or education. There was no significant between-country variation in these demographic associations.
An algorithm-derived diagnosis of aMCI showed few sociodemographic associations but was consistently associated with higher disability and neuropsychiatric symptoms in addition to showing substantial variation in prevalence across LAMIC populations. Longitudinal data are needed to confirm findings—in particular, to investigate the predictive validity of aMCI in these settings and risk/protective factors for progression to dementia; however, the large number affected has important implications in these rapidly ageing settings.
Please see later in the article for the Editors' Summary
Editors' Summary
Currently, more than 35 million people worldwide have dementia, a group of brain disorders characterized by an irreversible decline in memory, problem solving, communication, and other “cognitive” functions. Dementia, the commonest form of which is Alzheimer's disease, mainly affects older people and, because more people than ever are living to a ripe old age, experts estimate that, by 2050, more than 115 million people will have dementia. At present, there is no cure for dementia although drugs can be used to manage some of the symptoms. Risk factors for dementia include physical inactivity, infrequent participation in mentally or socially stimulating activities, and common vascular risk factors such as high blood pressure, diabetes, and smoking. In addition, some studies have reported that mild cognitive impairment (MCI) is associated with an increased risk of dementia. MCI can be seen as an intermediate state between normal cognitive aging (becoming increasingly forgetful) and dementia although many people with MCI never develop dementia, and some types of MCI can be static or self-limiting. Individuals with MCI have cognitive problems that are more severe than those normally seen in people of a similar age but they have no other symptoms of dementia and are able to look after themselves. The best studied form of MCI—amnestic MCI (aMCI)—is characterized by memory problems such as misplacing things and forgetting appointments.
Why Was This Study Done?
Much of the expected increase in dementia will occur in low and middle income countries (LAMICs) because these countries have rapidly aging populations. Given that aMCI is frequently used to define groups of people who may be at risk of developing dementia, it would be useful to know what proportion of community-dwelling older adults in LAMICs have aMCI (the prevalence of aMCI). Such information might help governments plan their future health care and social support needs. In this cross-sectional, population-based study, the researchers estimate the prevalence of aMCI in eight LAMICs using data collected by the 10/66 Dementia Research Group. They also investigate the association of aMCI with sociodemographic factors (for example, age, gender, and education), disability, and neuropsychiatric symptoms such as anxiety, apathy, irritability, and depression. A cross-sectional study collects data on a population at a single time point; the 10/66 Dementia Research Group is building an evidence base to inform the development and implementation of policies for improving the health and social welfare of older people in LAMICs, particularly people with dementia.
What Did the Researchers Do and Find?
In cross-sectional surveys carried out in six Latin American LAMICS, China, and India, more than 15,000 elderly individuals without dementia completed standardized assessments of their mental and physical health and their cognitive function. Interviews with relatives and carers provided further details about the participant's cognitive decline and about neuropsychiatric symptoms. The researchers developed an algorithm (set of formulae) that used the data collected in these surveys to diagnose aMCI in the study participants. Finally, they used statistical methods to analyze the prevalence, distribution, and impact of aMCI in the eight LAMICs. The researchers report that aMCI was associated with disability, anxiety, apathy, and irritability but not with depression and that the prevalence of aMCI ranged from 0.8% in China to 4.3% in India. Other analyses show that, considered across all eight countries, aMCI was modestly associated with being male (men had a slightly higher prevalence of aMCI than women) and with having fewer assets but was not associated with age or education.
What Do These Findings Mean?
These findings suggest that aMCI, as diagnosed using the algorithm developed by the researchers, is consistently associated with higher disability and with neuropsychiatric symptoms in the LAMICs studied but not with most sociodemographic factors. Because prevalidated and standardized measurements were applied consistently in all the countries and a common algorithm was used to define aMCI, these findings also suggest that the prevalence of aMCI varies markedly among LAMIC populations and is similar to or slightly lower than the prevalence most often reported for European and North American populations. Although longitudinal studies are now needed to investigate the extent to which aMCI can be used as risk marker for further cognitive decline and dementia in these settings, the large absolute numbers of older people with aMCI in LAMICs revealed here potentially has important implications for health care and social service planning in these rapidly aging and populous regions of the world.
Additional Information
Please access these Web sites via the online version of this summary at
Alzheimer's Disease International is the international federation of Alzheimer associations around the world; it provides links to individual associations, information about dementia, and links to three World Alzheimer Reports; information about the 10/66 Dementia Research Group is also available on this web site
The Alzheimer's Society provides information for patients and carers about dementia, including information on MCI and personal stories about living with dementia
The Alzheimer's Association also provides information for patients and carers about dementia and about MCI, and personal stories about dementia
A BBC radio program that includes an interview with a man with MCI is available
MedlinePlus provides links to further resources about MCI and dementia (in English and Spanish)
PMCID: PMC3274506  PMID: 22346736
7.  Brain metabolism and cognitive impairment in HIV infection: a 3 Tesla Magnetic Resonance Spectroscopy Study 
Magnetic resonance imaging  2010;28(9):1251-1257.
Background and Purpose
HIV-associated dementia (HAD) has been extensively studied using magnetic resonance spectroscopy (MRS) at field strengths of 1.5 Tesla (T). Higher magnetic field strengths (such as 3T) allow for more reliable determination of certain compounds, such as glutamate (Glu) and glutamine (Gln). The current study was undertaken to investigate the utility of 3T MRS for evaluating HIV+ patients with different levels of cognitive impairment with emphasis on the measurement of Glu and Glx (the sum of Glu and Gln).
Eighty six HIV+ subjects were evaluated at 3T using quantitative short echo time single voxel MRS of frontal white matter (FWM) and basal ganglia (BG). Subjects were divided into 3 groups according to the Memorial Sloan Kettering (MSK) HIV dementia stage: 21 had normal cognition (NC) (MSK 0), 31 had mild cognitive impairment (MCI) without dementia, (clinical MSK stage = 0.5) and 34 had dementia (HAD) (MSK > 1). HIV+ subjects had also undergone standardized cognitive testing covering the domains of executive function, verbal memory, attention, information processing speed, and motor and psychomotor speed. Between group differences in metabolite levels in FWM and BG were evaluated using ANOVA. Pearson correlation coefficients were used to explore the associations between the Glu and Glx metabolites and neurocognitive (NP) results.
FWM Glx (combined Glu and Gln) was lower in HAD (8.1±2.1 mM) compared to both the MCI (9.17±2.1 mM) and NC groups (10.0±1.6 mM), (P = 0.006). FWM myo-inositol (mI) was higher in HAD (4.15±0.75 mM) compared to both MCI (3.86±0.85 mM) and NC status (3.4±0.67 mM), (P = 0.006). FWM Glx/Creatine (Cr) was lower and FWM mI/Cr significantly higher in the HAD compared to MCI and NC groups (P = 0.01) and (P = 0.004) respectively. BG NAA was lower in the HAD group (6.79±1.53 mM), compared to the MCI (7.5±1.06 mM), and NC groups (7.6±1.01 mM), (P = 0.036). Significant negative correlations were observed between Glu, Glx, and NAA concentrations with Trail-making test B (P= 0.006, 0.0001, and 0.007 respectively) and significant positive correlation was found with Digit symbol test (P= 0.02, 0.002, and 0.008 respectively). FWM Glx and NAA concentrations showed negative correlation with Grooved pegboard non-dominant hand (P= 0.02 and 0.04 respectively).
Patients with HAD have lower levels of Glx concentrations and Glx/Cr ratio in FWM, which was associated with impaired performance in specific cognitive domains, including executive functioning, fine motor, attention and working memory performance. 3T MRS measurements of Glx may be a useful indicator of neuronal loss/dysfunction in patients with HIV infection.
PMCID: PMC2963667  PMID: 20688449
HIV Dementia; MR spectroscopy; Glutamate; Glx
8.  Differences between Early and Late-Onset Alzheimer’s Disease in Neuropsychological Tests 
Although patients with Alzheimer disease (AD) share clinical and histological features regardless of age of onset, the hypothesis that early onset AD constitutes a distinct subgroup prevails. Some authors suggest that early attention or language impairment constitute patterns of differentiation in terms of neuropsychological profile, between these groups. However, investigations are not consensual in terms of cognitive domains affected in each group. Aim: To investigate whether there is early neuropsychological difference between two types of AD using the conventional dividing line of 65 years. Methods: We evaluated the results obtained in the Mini-Mental State Examination (MMSE) and in a comprehensive neuropsychological battery – Battery of Lisbon for the Assessment of Dementia (BLAD), at a Dementia clinic in the University Hospital of Coimbra and a Memory Clinic. The study was developed in consecutive patients with a clinical probable diagnosis of mild to moderate AD, using standard criteria (DSMIV and NINCDS-ADRDA). Statistical analysis was performed using Qui-square and U-Mann–Whitney, for categorical and non-categorical variables. The degree of relation between variables, was measured using the coefficient of correlation rs de Spearman. Results: The total sample included 280 patients: 109 with early onset AD and 171 with a late-onset form. Groups were comparable in terms of gender, education or severity of disease, and MMSE. In BLAD, for univariate analysis the early onset group had lower scores in Naming (p = 0.025), Right–Left Orientation (p = 0.029) and Praxis (p = 0.001), and better performances in Orientation (p = 0.001) and Visual Memory (p = 0.022). After application of Bonferroni correction for multiple comparisons only Praxis and Orientation could differentiate the two groups. No significant differences were found in other tests or functions. Discussion: The results are suggestive of dissociated profiles between early and late-onset AD. Younger patients have a major impairment in Praxis and a tendency for a great impairment in neocortical temporal functions. AD patients with late-onset forms had a tendency for worse performances in Visual Memory and Orientation, suggesting a more localized disease to the limbic structures.
PMCID: PMC3350945  PMID: 22593755
early onset Alzheimer’s disease; late-onset Alzheimer’s disease; neuropsychological assessment; cognitive domains
9.  P300 and Neuropsychological Assessment in Mild Cognitive Impairment and Alzheimer Dementia 
Only a small proportion of individuals with Mild Cognitive Impairment (MCI) will convert to dementia. Methods currently available to identify risk for conversion do not combine enough sensitivity and specificity, which is even more problematic in low-educated populations. Current guidelines suggest the use of combined markers for dementia to enhance the prediction accuracy of assessment methods. The present study adhered to this proposal and investigated the sensitivity and specificity of the electrophysiological component P300 and standard neuropsychological tests to assess patients with Alzheimer’s disease (AD) and MCI recruited from a low-income country. The neuropsychological battery comprised tests of memory, attention, language, praxis, and executive functions. The P300 was recorded using a classical visual odd-ball paradigm. Three variables were found to achieve sensitivity and specificity values above 80% (Immediate and Delayed recall of word list – CERAD – and the latency of P300) for both MCI and AD. When they entered the model together (i.e., combined approach) the sensitivity for MCI increased to 96% and the specificity remained high (80%). Our preliminary findings suggest that the combined use of sensitive neuropsychological tasks and the analysis of the P300 may offer a very useful method for the preclinical assessment of AD, particularly in populations with low socioeconomic and educational levels. Our results provide a platform and justification to employ more resources to convert P300 and related parameters into a biological marker for AD.
PMCID: PMC3514532  PMID: 23227021
Alzheimer’s disease; mild cognitive impairment; event related potentials; P300; neuropsychology; early detection; preclinical markers
10.  Graph analysis of verbal fluency test discriminate between patients with Alzheimer's disease, mild cognitive impairment and normal elderly controls 
Verbal fluency is the ability to produce a satisfying sequence of spoken words during a given time interval. The core of verbal fluency lies in the capacity to manage the executive aspects of language. The standard scores of the semantic verbal fluency test are broadly used in the neuropsychological assessment of the elderly, and different analytical methods are likely to extract even more information from the data generated in this test. Graph theory, a mathematical approach to analyze relations between items, represents a promising tool to understand a variety of neuropsychological states. This study reports a graph analysis of data generated by the semantic verbal fluency test by cognitively healthy elderly (NC), patients with Mild Cognitive Impairment—subtypes amnestic (aMCI) and amnestic multiple domain (a+mdMCI)—and patients with Alzheimer's disease (AD). Sequences of words were represented as a speech graph in which every word corresponded to a node and temporal links between words were represented by directed edges. To characterize the structure of the data we calculated 13 speech graph attributes (SGA). The individuals were compared when divided in three (NC—MCI—AD) and four (NC—aMCI—a+mdMCI—AD) groups. When the three groups were compared, significant differences were found in the standard measure of correct words produced, and three SGA: diameter, average shortest path, and network density. SGA sorted the elderly groups with good specificity and sensitivity. When the four groups were compared, the groups differed significantly in network density, except between the two MCI subtypes and NC and aMCI. The diameter of the network and the average shortest path were significantly different between the NC and AD, and between aMCI and AD. SGA sorted the elderly in their groups with good specificity and sensitivity, performing better than the standard score of the task. These findings provide support for a new methodological frame to assess the strength of semantic memory through the verbal fluency task, with potential to amplify the predictive power of this test. Graph analysis is likely to become clinically relevant in neurology and psychiatry, and may be particularly useful for the differential diagnosis of the elderly.
PMCID: PMC4114204  PMID: 25120480
semantic verbal fluency; graph analysis; elderly; Alzheimer's disease; mild cognitive impairment
11.  Profile of Cognitive Complaints in Vascular Mild Cognitive Impairment and Mild Cognitive Impairment 
ISRN Neurology  2013;2013:865827.
Objective. Vascular mild cognitive impairment (VaMCI) is differentiated from mild cognitive impairment (MCI) by the presence of vascular events such as stroke or small vessel disease. Typically, MCI and VaMCI patients present with subjective complaints regarding cognition; however, little is known about the specific nature of these complaints. We aimed to create a profile of subjective cognitive complaints in MCI and VaMCI patients with similar levels of objective cognitive performance. Methods. Twenty MCI and twenty VaMCI patients were recruited from a Memory Disorders Clinic in Toronto. Subjective cognitive complaints were assessed and categorized using the Neuropsychological Impairment Scale. Results. MCI and VaMCI patients achieved similar scores on measures of objective cognitive function (P > 0.100). However, the VaMCI group had more subjective complaints than the MCI group (P = 0.050), particularly in the critical items, cognitive efficiency, memory, and verbal learning domains of the Neuropsychological Impairment Scale. Conclusions. Our findings support the idea that VaMCI and MCI differ in their clinical profiles, independent of neuroimaging. VaMCI patients have significantly more subjective cognitive complaints and may be exhibiting particular deficits in memory, verbal learning, and cognitive efficiency. Our findings promote the need for further research into VaMCI-specific cognitive deficits.
PMCID: PMC3830842  PMID: 24288623
12.  Cut-off Scores of a Brief Neuropsychological Battery (NBACE) for Spanish Individual Adults Older than 44 Years Old 
PLoS ONE  2013;8(10):e76436.
The neuropsychological battery used in Fundació ACE (NBACE) is a relatively brief, and easy to administer, test battery that was designed to detect cognitive impairment in the adulthood. The NBACE includes measures of cognitive information processing speed, orientation, attention, verbal learning and memory, language, visuoperception, praxis and executive functions. The aim of the present study was to establish the cut-off scores for impairment for different levels of age and education that could be useful in the cognitive assessment of Spanish subjects who are at risk for cognitive impairment, especially dementia. Data from 1018 patients with a mild dementia syndrome, and 512 cognitively healthy subjects, older than 44 years, from the Memory Clinic of Fundació ACE (Barcelona, Spain) were analyzed. In the whole sample, cut-off scores and sensitivity/specificity values were calculated for six conditions after combining 3 age ranges (44 to 64; 65 to 74; and older than 74 years old) by 2 educational levels (until Elementary school; and more than Elementary school). Moreover, general cut-offs are reported for Catalan and Spanish speakers. The results showed that most of NBACE tests reached good sensitivity and specificity values, except for Ideomotor praxis, Repetition and Verbal Comprehension tests, which had a ceiling effect. Word List Learning from the Wechsler Memory Scale-III and Semantic Verbal Fluency were the most useful tests to discriminate between cognitively healthy and demented subjects. The NBACE has been shown to be a useful tool able to detect cognitive impairment, especially dementia, in older than 44 years Spanish persons.
PMCID: PMC3797837  PMID: 24146868
13.  Mild cognitive impairment in Parkinson disease 
Neurology  2010;75(12):1062-1069.
In studies of mild cognitive impairment (MCI) in Parkinson disease (PD), patients without dementia have reported variable prevalences and profiles of MCI, likely to be due to methodologic differences between the studies.
The objective of this study was to determine frequency and the profile of MCI in a large, multicenter cohort of well-defined patients with PD using a standardized analytic method and a common definition of MCI.
A total of 1,346 patients with PD from 8 different cohorts were included. Standardized analysis of verbal memory, visuospatial, and attentional/executive abilities was performed. Subjects were classified as having MCI if their age- and education-corrected z score on one or more cognitive domains was at least 1.5 standard deviations below the mean of either control subjects or normative data.
A total of 25.8% of subjects (95% confidence interval [CI] 23.5–28.2) were classified as having MCI. Memory impairment was most common (13.3%; 11.6–15.3), followed by visuospatial (11.0%; 9.4–13.0) and attention/executive ability impairment (10.1%; 8.6–11.9). Regarding cognitive profiles, 11.3% (9.7–13.1) were classified as nonamnestic single-domain MCI, 8.9% (7.0–9.9) as amnestic single-domain, 4.8% (3.8–6.1) as amnestic multiple-domain, and 1.3% (0.9–2.1) as nonamnestic multiple-domain MCI. Having MCI was associated with older age at assessment and at disease onset, male gender, depression, more severe motor symptoms, and advanced disease stage.
MCI is common in patients with PD without dementia, affecting a range of cognitive domains, including memory, visual-spatial, and attention/executive abilities. Future studies of patients with PD with MCI need to determine risk factors for ongoing cognitive decline and assess interventions at a predementia stage.
= amnestic multiple-domain MCI;
= amnestic single-domain MCI;
= confidence interval;
= Diagnostic and Statistical Manual of Mental Disorders, 4th edition;
= mild cognitive impairment;
= Mini-Mental State Examination;
= nonamnestic multiple-domain MCI;
= nonamnestic single-domain MCI;
= Parkinson disease;
= Parkinson's Disease Cognitive Rating Scale;
= Unified Parkinson's Disease Rating Scale.
PMCID: PMC2942065  PMID: 20855849
14.  A Randomized Controlled Trial of Multicomponent Exercise in Older Adults with Mild Cognitive Impairment 
PLoS ONE  2013;8(4):e61483.
To examine the effect of multicomponent exercise program on memory function in older adults with mild cognitive impairment (MCI), and identify biomarkers associated with improvement of cognitive functions.
Methodology/Principal Findings
Subjects were 100 older adults (mean age, 75 years) with MCI. The subjects were classified to an amnestic MCI group (n = 50) with neuroimaging measures, and other MCI group (n = 50) before the randomization. Subjects in each group were randomized to either a multicomponent exercise or an education control group using a ratio of 1∶1. The exercise group exercised for 90 min/d, 2 d/wk, 40 times for 6 months. The exercise program was conducted under multitask conditions to stimulate attention and memory. The control group attended two education classes. A repeated-measures ANOVA revealed that no group × time interactions on the cognitive tests and brain atrophy in MCI patients. A sub-analysis of amnestic MCI patients for group × time interactions revealed that the exercise group exhibited significantly better Mini-Mental State Examination (p = .04) and logical memory scores (p = .04), and reducing whole brain cortical atrophy (p<.05) compared to the control group. Low total cholesterol levels before the intervention were associated with an improvement of logical memory scores (p<.05), and a higher level of brain-derived neurotrophic factor was significantly related to improved ADAS-cog scores (p<.05).
The results suggested that an exercise intervention is beneficial for improving logical memory and maintaining general cognitive function and reducing whole brain cortical atrophy in older adults with amnestic MCI. Low total cholesterol and higher brain-derived neurotrophic factor may predict improvement of cognitive functions in older adults with MCI. Further studies are required to determine the positive effects of exercise on cognitive function in older adults with MCI.
Trial Registration
UMIN-CTR UMIN000003662 ctr.cgi?function = brows&action = brows&type = summary&recptno = R000004436&language = J.
PMCID: PMC3621765  PMID: 23585901
15.  Neuropsychological characteristics of mild cognitive impairment subgroups 
To describe the neuropsychological characteristics of mild cognitive impairment (MCI) subgroups identified in the Cardiovascular Health Study (CHS) cognition study.
MCI was classified as MCI‐amnestic type (MCI‐AT): patients with documented memory deficits but otherwise normal cognitive function; and MCI‐multiple cognitive deficits type (MCI‐MCDT): impairment of at least one cognitive domain (not including memory), or one abnormal test in at least two other domains, but who had not crossed the dementia threshold. The MCI subjects did not have systemic, neurological, or psychiatric disorders likely to affect cognition.
MCI‐AT (n = 10) had worse verbal and non‐verbal memory performance than MCI‐MCDT (n = 28) or normal controls (n = 374). By contrast, MCI‐MCDT had worse language, psychomotor speed, fine motor control, and visuoconstructional function than MCI‐AT or normal controls. MCI‐MCDT subjects had memory deficits, though they were less pronounced than in MCI‐AT. Of the MCI‐MCDT cases, 22 (78.5%) had memory deficits, and 6 (21.5%) did not. MCI‐MCDT with memory disorders had more language deficits than MCI‐MCDT without memory disorders. By contrast, MCI‐MCDT without memory deficits had more fine motor control deficits than MCI‐MCDT with memory deficits.
The most frequent form of MCI was the MCI‐MCDT with memory deficits. However, the identification of memory impaired MCI groups did not reflect the true prevalence of MCI in a population, as 16% of all MCI cases and 21.5% of the MCI‐MCDT cases did not have memory impairment. Study of idiopathic amnestic and non‐amnestic forms of MCI is essential for an understanding of the aetiology of MCI.
PMCID: PMC2077558  PMID: 16103044
Alzheimer's disease; aging; dementia; mild cognitive impairment; neuropsychology
16.  Clinical Features of Mild Cognitive Impairment Differ in the Research and Tertiary Clinic Settings 
Comparative analysis of subjects with mild cognitive impairment (MCI) diagnosed in a primary research setting and those seen in a tertiary care memory disorders clinic.
Subjects who received a diagnosis of MCI between July 1, 2005, and December 31, 2006, in a longitudinal research study of normal cognition (n = 48) and patients diagnosed in a tertiary care referral clinic (n = 34) were evaluated using similar methodologies. Comparative analyses of detailed medical, neurological and neuropsychological data are presented.
The diagnosis of MCI was not accepted by 13 of 48 subjects (27%) classified as MCI in the primary research setting. Nondegenerative, potentially treatable causes of cognitive decline were found in 3 of 34 subjects (9%) seen in the tertiary referral clinic and in 11 of 35 subjects (31%) identified as MCI in the primary research setting (p = 0.02, Fisher’s exact test). MCI subjects identified in the primary research setting were older than those referred to the memory clinic (mean ± SD, 79.7 ± 7.0 vs. 71.5 ± 9.0 years, p < 0.0001, t test) and had more years of education (16.0 ± 3.2 vs. 13.6 ± 4.2 years, p < 0.01, t test). MCI subjects in the primary research setting appeared to be in a milder stage of disease, characterized by higher Mini-Mental State Examination scores (28.2 ± 1.8 vs. 25.7 ± 1.8, p < 0.0001), and a tendency towards single domain involvement, predominantly memory (mean number of domains involved, 1.0 vs. 2.5, p < 0.0001). More advanced stages of MCI, seen in the tertiary referral population, had additional involvement of attention (p < 0.0001, Fisher’s exact test) and visuospatial domains (p < 0.0002, Fisher’s exact test). Semiquantitative grading of hippocampal and medial temporal lobe atrophy did not differ between groups (p = 0.81, Mann-Whitney U test).
The diagnosis of MCI may be unwelcome in naïve persons. Remedial causes of MCI should be actively investigated. Demographic and clinical characteristics of MCI differ between research subjects and patients referred to a tertiary care clinic.
PMCID: PMC2667338  PMID: 18724049
Mild cognitive impairment; Alzheimer’s disease; Cognitive domain
17.  Default mode network connectivity in stable vs progressive mild cognitive impairment 
Neurology  2011;76(6):511-517.
Dysfunction of the default mode network (DMN) has been identified in prior cross-sectional fMRI studies of Alzheimer disease (AD) and mild cognitive impairment (MCI); however, no studies have examined its utility in predicting future cognitive decline.
fMRI scans during a face–name memory task were acquired from a cohort of 68 subjects (25 normal control, 31 MCI, and 12 AD). Subjects with MCI were followed for 2.4 years (±0.8) to determine progression to AD. Maps of DMN connectivity were compared with a template DMN map constructed from elderly normal controls to obtain goodness-of-fit (GOF) indices of DMN expression. Indices were compared between groups and correlated with cognitive decline.
GOF indices were highest in normal controls, intermediate in MCI, and lowest in AD (p < 0.0001). In a predictive model (that included baseline GOF indices, age, education, Mini-Mental State Examination score, and an index of DMN gray matter volume), the effect of GOF index on progression from MCI to dementia was significant. In MCI, baseline GOF indices were correlated with change from baseline in functional status (Clinical Dementia Rating–sum of boxes) (r = −0.40, p < 0.04). However, there was no additional predictive value for DMN connectivity when baseline delayed recall was included in the models.
fMRI connectivity indices distinguish patients with MCI who undergo cognitive decline and conversion to AD from those who remain stable over a 2- to 3-year follow-up period. Our data support the notion of different functional brain connectivity endophenotypes for “early” vs “late” MCI, which are associated with different baseline memory scores and different rates of progression and conversion.
PMCID: PMC3053179  PMID: 21228297
18.  Characterizing mild cognitive impairment in incident Parkinson disease 
Neurology  2014;82(4):308-316.
To describe the frequency of mild cognitive impairment (MCI) in Parkinson disease (PD) in a cohort of newly diagnosed incident PD cases and the associations with a panel of biomarkers.
Between June 2009 and December 2011, 219 subjects with PD and 99 age-matched controls participated in clinical and neuropsychological assessments as part of a longitudinal observational study. Consenting individuals underwent structural MRI, lumbar puncture, and genotyping for common variants of COMT, MAPT, SNCA, BuChE, EGF, and APOE. PD-MCI was defined with reference to the new Movement Disorder Society criteria.
The frequency of PD-MCI was 42.5% using level 2 criteria at 1.5 SDs below normative values. Memory impairment was the most common domain affected, with 15.1% impaired at 1.5 SDs. Depression scores were significantly higher in those with PD-MCI than the cognitively normal PD group. A significant correlation was found between visual Pattern Recognition Memory and cerebrospinal β-amyloid 1–42 levels (β standardized coefficient = 0.350; p = 0.008) after controlling for age and education in a linear regression model, with lower β-amyloid 1–42 and 1–40 levels observed in those with PD-MCI. Voxel-based morphometry did not reveal any areas of significant gray matter loss in participants with PD-MCI compared with controls, and no specific genotype was associated with PD-MCI at the 1.5-SD threshold.
In a large cohort of newly diagnosed PD participants, PD-MCI is common and significantly correlates with lower cerebrospinal β-amyloid 1–42 and 1–40 levels. Future longitudinal studies should enable us to determine those measures predictive of cognitive decline.
PMCID: PMC3929202  PMID: 24363137
19.  The Beijing version of the montreal cognitive assessment as a brief screening tool for mild cognitive impairment: a community-based study 
BMC Psychiatry  2012;12:156.
A cross-sectional validation study was conducted in several urban and rural communities in Beijing, China, to evaluate the effectiveness of the Beijing version of the Montreal Cognitive Assessment (MoCA-BJ) as a screening tool to detect mild cognitive impairment (MCI) among Chinese older adults.
The MoCA-BJ and the Mini-Mental State Examination (MMSE) were administered to 1001 Chinese elderly community dwellers recruited from three different regions (i.e., newly developed, old down-town, and rural areas) in Beijing. Twenty-one of these participants were diagnosed by experienced psychiatrists as having dementia, 115 participants were diagnosed as MCI, and 865 participants were considered to be cognitively normal. To analyze the effectiveness of the MoCA-BJ, we examined its psychometric properties, conducted item analyses, evaluated the sensitivity and specificity of the scale, and compared the scale with the MMSE. Demographic and regional differences among our subjects were also taken into consideration.
Under the recommended cut-off score of 26, the MoCA-BJ demonstrated an excellent sensitivity of 90.4%, and a fair specificity (31.3%). The MoCA-BJ showed optimal sensitivity (68.7%) and specificity (63.9%) when the cut-off score was lowered to 22. Among all the seven cognitive sub-domains, delayed recall was shown to be the best index to differentiate MCI from the normal controls. Regional differences disappeared when the confounding demographic variables (i.e., age and education) were controlled. Item analysis showed that the internal consistency was relatively low in both naming and sentence repetition tasks, and the diagnostic accuracy was similar between the MoCA-BJ and the MMSE.
In general, the MoCA-BJ is an acceptable tool for MCI screening in both urban and rural regions of Beijing. However, presumably due to the linguistic and cultural differences between the original English version and the Chinese version of the scale, and the lower education level of Chinese older adults, the MoCA-BJ is not much better than the MMSE in detecting MCI, at least for this study sample. Further modifications to several test items of the MoCA-BJ are recommended in order to improve the applicability and effectiveness of the MoCA-BJ in MCI screening among the Chinese population.
PMCID: PMC3499377  PMID: 23009126
MoCA-BJ; MMSE; Mild cognitive impairment; Dementia; Cognitive assessment
20.  Defining optimal cutoff scores for cognitive impairment using MDS Task Force PD-MCI criteria 
The recently proposed Movement Disorder Society (MDS) Task Force diagnostic criteria for mild cognitive impairment in Parkinson’s disease (PD-MCI) represent a first step towards a uniform definition of PD-MCI across multiple clinical and research settings. Several questions regarding specific criteria, however, remain unanswered including optimal cutoff scores by which to define impairment on neuropsychological tests.
Seventy-six non-demented PD patients underwent comprehensive neuropsychological assessment and were classified as PD-MCI or PD with normal cognition (PD-NC). Concordance of PD-MCI diagnosis by MDS Task Force Level II criteria (comprehensive assessment), using a range of standard deviation (SD) cutoff scores, was compared to our consensus diagnosis of PD-MCI or PD-NC. Sensitivity, specificity, positive and negative predictive values were examined for each cutoff score. PD-MCI subtype classification and distribution of cognitive domains impaired were evaluated.
Concordance for PD-MCI diagnosis was greatest for defining impairment on neuropsychological tests using a 2 SD cutoff score below appropriate norms. This cutoff also provided the best discriminatory properties for separating PD-MCI from PD-NC, compared to other cutoff scores. With the MDS PD-MCI criteria, multiple domain impairment was more frequent than single domain impairment, with predominant executive function, memory, and visuospatial function deficits.
Application of the MDS Task Force PD-MCI Level II diagnostic criteria demonstrates good sensitivity and specificity at a 2 SD cutoff score. The predominance of multiple domain impairment in PD-MCI with the Level II criteria suggests not only influences of testing abnormality requirements, but also the widespread nature of cognitive deficits within PD-MCI.
PMCID: PMC4164432  PMID: 24123267
Executive function; MCI (mild cognitive impairment); Memory; Neuropsychological tests; Parkinson’s disease
21.  Verbal Prompting To Improve Everyday Cognition in MCI and Unimpaired Older Adults 
Neuropsychology  2013;28(1):123-134.
This study investigated the effect of verbal prompting on elders’ 10-year longitudinal change in everyday cognition. Differential effects of prompting associated with impaired cognitive status were also examined.
At baseline, 2,802 participants (mean age=73.6 years, mean education=13.5 years) from the ACTIVE clinical trial were classified as unimpaired, having amnestic mild cognitive impairment (MCI) or non-amnestic MCI based on psychometric algorithm. Participants were given the Observed Tasks of Daily Living (OTDL; a behavioral measure with tasks involving medication management/finances/telephone use) at baseline and at 1-, 2-, 3-, 5-, and 10-year follow-ups. When participants said “I don’t know” or did not respond to an item, they received a standardized verbal prompt. At each occasion, Unprompted (sum of items correct without prompting) and Prompted (sum of items correct including both prompted and unprompted) scores were derived for each participant. Multi-level modeling, adjusting for demographics/health/training group, was used to determine the trajectories of OTDL performance.
In general, persons with MCI performed at lower levels than those who were unimpaired (amnestic
Very simple prompting appears to enhance and maintain performance on a task of everyday cognition over 10 years for both unimpaired and mildly-impaired older adults.
PMCID: PMC3935329  PMID: 24219613
everyday cognition; verbal prompting; cognitive impairment; cognitive aging; longitudinal follow-up
Neuropsychologia  2011;49(14):3826-3830.
The current study investigated the relationship between bilingual language proficiency and onset of probable Alzheimer’s disease (AD) in 44 Spanish-English bilinguals at the UCSD Alzheimer’s Disease Research Center. Degree of bilingualism along a continuum was measured using Boston Naming Test (BNT) scores in each language. Higher degrees of bilingualism were associated with increasingly later age-of-diagnosis (and age of onset of symptoms), but this effect was driven by participants with low education level (a significant interaction between years of education and bilingualism) most of whom (73%) were also Spanish-dominant. Additionally, only objective measures (i.e., BNT scores), not self-reported degree of bilingualism, predicted age-of-diagnosis even though objective and self-reported measures were significantly correlated. These findings establish a specific connection between knowledge of two languages and delay of AD onset, and demonstrate that bilingual effects can be obscured by interactions between education and bilingualism, and by failure to obtain objective measures of bilingualism. More generally, these data support analogies between the effects of bilingualism and “cognitive reserve” and suggest an upper limit on the extent to which reserve can function to delay dementia.
PMCID: PMC3223277  PMID: 22001315
We examined whether recognition of facial emotional expression would be affected in amnestic mild cognitive impairment (aMCI). A total of 50 elderly persons met the initial inclusion criteria, 10 were subsequently excluded (Geriatric Depression Score >5). 22 subjects were classified with aMCI based on published criteria (single domain aMCI [SD-aMCI], n = 10; multiple domain aMCI [MD-aMCI], n = 12); 18 subjects were cognitively normal. All underwent standard neurological and neuropsychological evaluations as well as tests of facial emotion recognition (FER) and famous faces identification (FFI). Among normal controls, FFI was negatively correlated with MMSE and positively correlated with executive function. Among patients with aMCI, FER was correlated with attention/speed of processing. No other correlations were significant. In a multinomial logistic regression model adjusted for age, sex, and education, a poorer score on FER, but not on FFI, was associated with greater odds of being classified as MD-aMCI (odds ratio [OR], 3.82; 95% confidence interval [CI], 1.05–13.91; p = 0.042). This association was not explained by memory or global cognitive score. There was no association between FER or FFI and SD-aMCI (OR, 1.13; 95% CI, 0.36–3.57; p = 0.836). Therefore, FER, but not FFI, may be impaired in MD-aMCI. This implies that in MD-aMCI, the tasks of FER and FFI may involve segregated neurocognitive networks.
PMCID: PMC3918473  PMID: 22954669
assessment of cognitive disorders/dementia; cognitive aging; emotion; mild cognitive impairment; neuropsychiatric symptoms
Current Alzheimer research  2014;11(5):494-500.
With age, performance of motor tasks becomes more reliant on cognitive resources to compensate for the structural and functional declines in the motor control regions in the brain. We hypothesized that participants with amnestic mild cognitive impairment (aMCI) are more prone to motor dysfunctions than cognitively normal older adults under dual-task conditions where competitive demands challenge cognitive functions while performing a motor task simultaneously.
Sixteen aMCI participants (females=9, age=64±5yrs, clinical dementia rating score=0.5) and 10 age- and education-matched cognitively normal adults (females=5, age=62±6yrs) participated. Using a 10-meter-walk test (10MW), gait velocity was recorded at baseline and under 4 different dual-task (DT) conditions designed to challenge working memory, executive function, and episodic memory. Specifically, DT1: verbal fluency; DT2: 5-digit backward span; DT3: serial-7 subtraction; and DT4: 3-item delayed recall. Physical function was measured by Timed Up-and-Go (TUG), simple reaction time (RT) to a free-falling yardstick, and functional reach (FR).
No difference was found in physical functions, aerobic fitness, and exercise cardiopulmonary responses between aMCI participants and controls. However, aMCI participants showed more pronounced gait slowing from baseline when compared to the controls (p<0.05; p=0.001; p<0.001; p<0.001, respectively).
Our finding supports the theory of shared resource of motor and cognitive control. Participants with aMCI manifested more gait slowing than cognitively-normal older adults under DT conditions, with the largest differences during tests of working and episodic memory. The outcome of dual-task assessment shows promise as a potential marker for detection of aMCI and early Alzheimer disease.
PMCID: PMC4082490  PMID: 24801217
Dual-task; early detection; gait; mild cognitive impairment; motor control
Alzheimer disease and associated disorders  2013;27(4):10.1097/WAD.0b013e31827bde32.
Psychometric definitions of mild cognitive impairment (MCI) typically use cut-off levels set at 1.5 standard deviations below age- and education-adjusted norms, assuming that the education adjustment accounts for premorbid abilities. However, non-cognitive factors impact educational attainment, potentially leading to incorrect categorization as MCI. We examined whether using an adjustment based on reading performance (Wide Range Achievement Test [WRAT] Reading) improved MCI diagnostic accuracy.
935 Framingham Offspring (mean age 72 ± 5) underwent tests of Memory, Executive Function, Abstraction, Language, and Visuospatial Function as part of a neuropsychological test battery. Domain-specific test scores were regressed onto age and WRAT score, or education, to define MCI. Survival analyses were used to relate baseline MCI to incident dementia.
The two MCI definitions differed most for the lowest and highest education groups. The WRAT definition was more strongly associated with incident dementia for all five tests. MCI-level Abstraction performance was associated with incident dementia using the WRAT definition (HR = 3.20, p = .033), but not the education definition (HR = 1.19, p = .814).
The WRAT should be considered along with the standard measure of years of education, as it may be a better surrogate marker of premorbid abilities.
PMCID: PMC3626741  PMID: 23314066
Mild cognitive impairment; premorbid abilities; neuropsychological assessment; Alzheimer's disease; longitudinal

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