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1.  Predicting cognitive change within domains 
The Clinical neuropsychologist  2010;24(5):779-792.
Standardized regression based (SRB) formulas, a method for predicting cognitive change across time, traditionally use baseline performance on a neuropsychological measure to predict future performance on that same measure. However, there are instances in which the same tests may not be given at follow-up assessments (e.g., lack of continuity of provider, avoiding practice effects). The current study sought to expand this methodology by developing SRBs to predict performance on different tests within the same cognitive domain. Using a sample of 127 non-demented community-dwelling older adults assessed at baseline and after one year, two sets of SRBs were developed: 1. those predicting performance on the same test, and 2. those predicting performance on a different test within the same cognitive domain. The domains examined were learning and memory, processing speed, and language. Across both sets of SRBs, one year scores were significantly predicted by baseline scores, especially for the learning and memory and processing speed measures. Although SRBs developed for the same test were comparable to those developed for different tests within the same domain, less variance was accounted for as tests became less similar. The current results lend preliminary support for additional development of SRBs, both for same- and different-tests, as well as beginning to examine domain-based SRBs.
PMCID: PMC2893275  PMID: 20358479
Predicting cognition; standardized based regression
2.  The Impact of Adjuvant Brachytherapy with Sublobar Resection on Pulmonary Function and Dyspnea in High-risk Operable Patients; Preliminary results from the ACOSOG Z4032 Trial 
Z4032 is a randomized clinical trial conducted by the American College of Surgeons Oncology Group that compared sublobar resection alone (SR) to sublobar resection with brachytherapy (SRB) for high-risk operable patients with non-small cell lung cancer (NSCLC). This current report evaluate the early impact that adjuvant brachytherapy has on pulmonary function tests (PFT), dyspnea and perioperative (30-day) respiratory complications on this impaired patient population.
Eligible stage I NSCLC patients with tumors 3cm or less were randomized to SR or SRB. The outcomes measured included the % predicted forced expiratory volume (FEV1%), % predicted carbon monoxide diffusion capacity (DLCO%), dyspnea score using the UC San Diego Shortness of Breath Questionnaire. Pulmonary morbidity was assessed using the Common Terminology Criteria for Adverse Events (AE) Version 3.0 (CTCAE). Outcomes were measured at baseline, and at 3-months. A 10% change in PFT or a 10-point change in dyspnea score was deemed clinically meaningful.
Z4032 permanently closed to patient accrual in January 2010 with a total of 224 patients. At 3-month follow-up, PFT data is currently available on 148 (74 SR/74 SRB) patients described in this report. There were no differences in baseline characteristics between the arms. In the SR arm, 9 (12%) patients reported grade-3 respiratory AE compared to 12 (16%) in the SRB arm (p=0.49). There was no significant change in the percent change in DLCO%, or dyspnea score from baseline to 3-month within either arm. In the case of FEV1%, the percent change from baseline to 3-month was significant within SR arm (p=0.03), with patients reporting an improvement in the FEV1% at month 3. Multivariable regression analysis (adjusted for baseline values) showed no significant impact of treatment arm, tumor location (upper versus other lobe), or surgical approach (VATS versus thoracotomy) on the 3-month values for FEV1%, DLCO% and dyspnea scores. There was no significant difference in the incidence of clinically meaningful (10% PFT change, or 10-point dyspnea score) change between the two arms. Twenty-two percent of patients with lower lobe tumors compared to 9% with upper lobe tumors demonstrated a 10% decline in FEV1% (odds ratio 2.79; 95 CI=1.07 – 7.25; p=0.04).
Adjuvant intraoperative brachytherapy performed in conjunction with sublobar resection does not significantly worsen pulmonary function, or dyspnea at 3-months in a high-risk population with NSCLC. SRB was not associated with increased perioperative pulmonary AE. Lower-lobe resection was the only factor that was significantly associated with a clinically meaningful decline in FEV1%.
PMCID: PMC3156868  PMID: 21724195
3.  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
4.  Methodological Challenges in Determining Longitudinal Associations Between Anticholinergic Drug Use and Incident Cognitive Decline 
To compare the effect of using different anticholinergic drug scales and different models of cognitive decline in longitudinal studies.
Longitudinal cohort study.
Outpatient clinics, Quebec, Canada.
Individuals aged 60 and older without dementia or depression (n = 102).
Using baseline and 1-year follow-up data, four measures of anticholinergic burden (anticholinergic component of the Drug Burden Index (DBI-Ach), Anticholinergic Cognitive Burden (ACB), Anticholinergic Drug Scale (ADS), and Anticholinergic Risk Scale (ARS)) were applied. Three models of cognitive decline (worsening of raw neuropsychological test scores, Reliable Change Index (RCI), and a standardized regression based measure (SRB)) were compared in relation to Diagnostic and Statistical Manual of Mental Disorders, Fifth Edition (DSM-V) criteria for the onset of a new mild neurocognitive disorder. The consistency of associations was examined using logistic regression.
The frequency of identifying individuals with an increase in anticholinergic burden over 1 year varied from 18% with the DBI-Ach to 23% with the ACB. The frequency of identifying cognitive decline ranged from 8% to 86% using different models. The raw change score had the highest sensitivity (0.91), and the RCI the highest specificity (0.93) against DSM-V criteria. Memory decline using the SRB method was associated with an increase in ACB (odds ratio (OR) = 5.3, 95% confidence interval (CI) = 1.1–25.8), ADS (OR = 5.7, 95% CI = 1.1–27.7), and ARS (OR = 6.5, 95% CI = 1.34–32.3). An increase in the DBI-Ach was associated with a decline on memory testing using the raw change score method (OR = 4.2, 95% CI = 1.8–15.4) and on the Trail-Making Test Part B using SRB (OR = 2.9, 95% CI = 1.1–8.0). No associations were observed using the DSM-V criteria or RCI method.
The choice of different methods for defining drug exposure and cognitive decline will have a significant effect on the results of pharmacoepidemiological studies.
PMCID: PMC4233958  PMID: 24417438
anticholinergic drug exposure; cognitive decline; longitudinal study; older adults; methods
5.  Normative data and validation of a regression based summary score for assessing meaningful neuropsychological change 
Reliable detection and quantification of longitudinal cognitive change are of considerable importance in many neurological disorders, particularly to monitor central nervous system effects of disease progression and treatment. In the current study, we developed normative data for repeated neuropsychological (NP) assessments (6 testings) using a modified Standard Regression-Based (SRB) approach in a sample that includes both HIV-uninfected (HIV−, N=172) and neuromedically stable HIV-infected (HIV+, N=124) individuals. Prior analyzes indicated no differences in NP change between the infected and uninfected participants. The norms for change included correction for factors found to significantly affect follow-up performance, using hierarchical regression. The most robust and consistent predictors of follow-up performance were the prior performance on the same test (which contributed in all models) and a measure of prior overall NP competence (predictor in 97% of all models). Demographic variables were predictors in 10%-46% of all models and in small amounts; while test retest interval contributed in only 6% of all models. Based on the regression equations, standardized change scores (z-scores) were computed for each test measure at each interval; these z scores were then averaged to create a total battery change score. An independent sample of HIV− participants who had completed 8 of the 15 tests was used to validate an abridged summary change score. The normative data are available in an electronic format by email request to the first author. Correction for practice effects based on normative data improved the consistency of NP impairment classification in a clinically stable longitudinal cohort after baseline.
PMCID: PMC3151558  PMID: 21391011
Normative data; longitudinal studies; regression; regression change score; SRB; practice effect
6.  Cognitive Correlates of Functional Performance in Older Adults: Comparison of Self-Report, Direct Observation, and Performance-Based Measures 
Neuropsychologists are often asked to answer questions about the effects of cognitive deficits on everyday functioning. This study examined the relationship between and the cognitive correlates of self-report, performance-based, and direct observation measures commonly used as proxy measures for everyday functioning. Participants were 88 community-dwelling, cognitively healthy older adults (age 50–86 years). Participants completed standardized neuropsychological tests and questionnaires, and performed eight activities of daily living (e.g., water plants, fill a medication dispenser) while under direct observation in a campus apartment. All proxy measures of everyday function were sensitive to the effects of healthy cognitive aging. After controlling for age, cognitive predictors explained a unique amount of the variance for only the performance-based behavioral simulation measure (i.e., Revised Observed Tasks of Daily Living). The self-report instrumental activities of daily living (IADL) and the performance-based everyday problem-solving test (i.e., EPT) did not correlate with each other; however, both were unique predictors of the direct observation measure. These findings suggest that neuropsychologists must be cautious in making predictions about the quality of everyday activity completion in cognitively healthy older adults from specific cognitive functions. The findings further suggest that a self-report of IADLs and the performance-based EPT may be useful measures for assessing everyday functional status in cognitively healthy older adults.
PMCID: PMC3736729  PMID: 21729400
Activities of daily living; Cognitive correlates; Functional status; Aging; Instrumental activities of daily living; Everyday functioning
7.  The Sticky Resting Box, a new tool for studying resting behaviour of Afrotropical malaria vectors 
Parasites & Vectors  2014;7:247.
Monitoring densities of adult mosquito populations is a major challenge in efforts to evaluate the epidemiology of mosquito-borne diseases, and their response to vector control interventions. In the case of malaria, collection of outdoor-resting Anophelines is rarely incorporated into surveillance and control, partially due to the lack of standardized collection tools. Such an approach, however, is increasingly important to investigate possible changes in mosquito behaviour in response to the scale up of Insecticide Treated Nets and Indoor Residual Spraying. In this study we evaluated the Sticky Resting Box (SRB) - i.e. a sticky variant of previously investigated mosquito Resting Box, which allows passive collection of mosquitoes entering the box – and compared its performance against traditional methods for indoor and outdoor resting mosquito sampling.
Daily collections were carried out in two neighbouring villages of Burkina Faso during rainy season 2011 and dry season 2012 by SRB located indoors and outdoors, and by Back-Pack aspiration inside houses (BP) and in ad hoc built outdoor pit-shelters (PIT).
Overall, almost 20,000 Culicidae specimens belonging to 16 species were collected and morphologically identified. Malaria vectors included Anopheles coluzzii (53%), An. arabiensis (12%), An. gambiae s.s. (2.0%) and An. funestus (4.5%). The diversity of species collected in the two villages was similar for SRB and PIT collections outdoors, and significantly higher for SRB than for BP indoors. The population dynamics of An. gambiae s.l. mosquitoes, as obtained by SRB-collections was significantly correlated with those obtained by the traditional methods. The predicted mean estimates of An. gambiae s.l. specimens/sampling-unit/night-of-collections was 6- and 5-times lower for SRB than for BP indoors and PIT outdoors, respectively.
Overall, the daily performance of SRB in terms of number of malaria vectors/trap was lower than that of traditionally used approaches for in- and outdoor collections. However, unlike these methods, SRB could be set up to collect mosquitoes passively over at least a week. This makes SRB a promising tool for passively monitoring anopheline resting populations, with data presented here providing guidance for how to set up SRB-based collections to acquire information comparable to those obtained with other methods.
PMCID: PMC4049408  PMID: 24885432
Anopheles gambiae; Malaria; Resting behaviour; Mosquito sampling; Sticky trap; Ecology
8.  Practice effects predict cognitive outcome in amnestic Mild Cognitive Impairment 
Practice effects on cognitive tests have been shown to further characterize patients with amnestic Mild Cognitive Impairment (aMCI), and may provide predictive information about cognitive change across time. We tested the hypothesis that a loss of practice effects would portend a worse prognosis in aMCI.
Longitudinal, observational design following participants across one year.
Community-based cohort.
Three groups of older adults: 1. cognitively intact (n=57), 2. aMCI with large practice effects across one week (MCI+PE, n=25), and 3. aMCI with minimal practice effects across one week (MCI−PE, n=26).
Neuropsychological tests.
After controlling for age and baseline cognitive differences, the MCI−PE group performed significantly worse than the other groups after one year on measures of immediate memory, delayed memory, language, and overall cognition.
Although these results need to be replicated in larger samples, the loss of short-term practice effects portends a worse prognosis in patients with aMCI.
PMCID: PMC3202689  PMID: 22024617
Mild Cognitive Impairment; practice effects; dementia
9.  Neuropsychological Predictors of Dementia in Late-Life Major Depressive Disorder 
Major Depressive Disorder (MDD) is a likely risk factor for dementia, but some cases of MDD in older adults may actually represent a prodrome of this condition. The purpose of this study was to use neuropsychological test scores to predict conversion to dementia in a sample of depressed older adults diagnosed as nondemented at time of neuropsychological testing.
Longitudinal, with mean follow-up of 5.45 years.
Outpatient depression treatment study at Duke University
30 nondemented individuals depressed at time of neuropsychological testing and later diagnosed with incident dementia; 149 nondemented individuals depressed at time of neuropsychological testing and a diagnosis of cognitively normal.
All participants received clinical assessment of depression, were assessed to rule out prevalent dementia at time of study enrollment, completed neuropsychological testing at time of study enrollment, and were diagnosed for cognitive disorders on an annual basis.
Non-demented, acutely depressed older adults who converted to dementia during the study period exhibited broadly lower cognitive performances at baseline than acutely depressed individuals who remained cognitively normal. Discriminant function analysis indicated that 2 neuropsychological tests, CERAD Recognition Memory and Trail Making B, best predicted dementia conversion.
Depressed older adults with cognitive deficits in the domains of memory and executive functions during acute depression are at higher risk for developing dementia. Some cases of late-life depression may reflect a prodrome of dementia in which clinical manifestation of mood changes may co-occur with emerging cognitive deficits.
PMCID: PMC3376682  PMID: 23395197
geriatric depression; dementia; neuropsychology; memory; executive function
10.  A Randomised, Blinded, Placebo-Controlled Trial in Dementia Patients Continuing or Stopping Neuroleptics (The DART-AD Trial)  
PLoS Medicine  2008;5(4):e76.
There have been increasing concerns regarding the safety and efficacy of neuroleptics in people with dementia, but there are very few long-term trials to inform clinical practice. The aim of this study was to determine the impact of long-term treatment with neuroleptic agents upon global cognitive decline and neuropsychiatric symptoms in patients with Alzheimer disease.
Methods and Findings
Design: Randomised, blinded, placebo-controlled parallel two-group treatment discontinuation trial.
Setting: Oxfordshire, Newcastle and Gateshead, London and Edinburgh, United Kingdom.
Participants: Patients currently prescribed the neuroleptics thioridazine, chlorpromazine, haloperidol trifluoperazine or risperidone for behavioural or psychiatric disturbance in dementia for at least 3 mo.
Interventions: Continue neuroleptic treatment for 12 mo or switch to an identical placebo.
Outcome measures: Primary outcome was total Severe Impairment Battery (SIB) score. Neuropsychiatric symptoms were evaluated with the Neuropsychiatric Inventory (NPI).
Results: 165 patients were randomised (83 to continue treatment and 82 to placebo, i.e., discontinue treatment), of whom 128 (78%) commenced treatment (64 continue/64 placebo). Of those, 26 were lost to follow-up (13 per arm), resulting in 51 patients per arm analysed for the primary outcome. There was no significant difference between the continue treatment and placebo groups in the estimated mean change in SIB scores between baseline and 6 mo; estimated mean difference in deterioration (favouring placebo) −0.4 (95% confidence interval [CI] −6.4 to 5.5), adjusted for baseline value (p = 0.9). For neuropsychiatric symptoms, there was no significant difference between the continue treatment and placebo groups (n = 56 and 53, respectively) in the estimated mean change in NPI scores between baseline and 6 mo; estimated mean difference in deterioration (favouring continue treatment) −2.4 (95% CI −8.2 to 3.5), adjusted for baseline value (p = 0.4). Both results became more pronounced at 12 mo. There was some evidence to suggest that those patients with initial NPI ≥ 15 benefited on neuropsychiatric symptoms from continuing treatment.
For most patients with AD, withdrawal of neuroleptics had no overall detrimental effect on functional and cognitive status. Neuroleptics may have some value in the maintenance treatment of more severe neuropsychiatric symptoms, but this benefit must be weighed against the side effects of therapy.
Trial registration: Cochrane Central Registry of Controlled Trials/National Research Register (#ISRCTN33368770).
In a randomized trial of patients with dementia, Clive Ballard and colleagues show that withdrawal of neuroleptics had no overall detrimental effect, and by some measures improved, functional and cognitive status.
Editors' Summary
The number of people with dementia (currently 25 million worldwide) is expected to increase by 5 million each year. The risk of dementia, including Alzheimer disease, increases sharply with age: Alzheimer's Disease International estimates that 1.4% of people 65–69 have dementia, whereas almost a full quarter of those over the age of 85 years are affected. Almost all older dementia patients will experience, along with the cognitive and functional decline typical of the illness, some neuropsychiatric symptoms. These symptoms can include agitation, aggression, and psychosis, and are often devastating for the older patient and his or her family and caregiver. Managing these symptoms is often a prime concern for health-care providers and families. Neuroleptics (sometimes called antipsychotics) are the class of drugs often used to manage or control neuropsychiatric problems, but there have been questions about their safety and appropriateness. Safety concerns involve risk of stroke, parkinsonism, sedation, edema, and chest infections but also include a worsening of cognitive decline with prolonged use of neuroleptics.
Why Was the Study Done?
Previous studies on the effectiveness and safety of neuroleptics in older people have been short term. Ballard and colleagues wanted to study over a longer period of time the impact of neuroleptic drugs on elderly patients with dementia. Specifically, they wanted to know if being on a neuroleptic was associated with more cognitive decline than coming off the drug. They also wanted to investigate whether discontinuing the drug exacerbated any neuropsychiatric symptoms, Parkinson disease-like symptoms, or other functional, language, and cognition difficulties frequently associated with dementia.
What Did the Researchers Do and Find?
The researchers recruited older patients with Alzheimer disease from across England who had been on neuroleptics for at least three months. They randomised patients to one of two groups: the first group continued taking the same neuroleptic at the same dosage level while the second group was switched to an identical-looking placebo. The researchers assessed the patients' cognitive status and neuropsychiatric symptoms upon their entry into the study. Six and 12 months later the researchers assessed any cognitive decline and the level of neuropsychiatric and other problems that patients were experiencing.
At both 6 and 12 months, the researchers found that there were no differences between the two groups (continued treatment and placebo) in terms of cognitive decline. The placebo group may have had less cognitive decline, but this was not statistically significant. They also found no overall differences between the two groups in the change in the number of neuropsychiatric symptoms over these time periods. Patients with severe neuropsychiatric problems at the outset of the trial did better on continued neuroleptic therapy, but this advantage was not statistically significant. There was a significant decline on the verbal fluency language tests among the patients who continued on their neuroleptic.
What Do these Findings Mean?
The researchers report perhaps the first trial of this duration on continued versus withdrawn neuroleptic treatment among older dementia patients. The findings do not indicate any benefit of continuing neuroleptic therapies in older patients on either cognitive or neuropsychiatric outcomes. The researchers conclude that neuroleptics, with their known safety issues, should not be used as first-line treatment to manage problems such as agitation or aggression. For older dementia patients whose neuropsychiatric symptoms are not remedied by nonpharmaceutical treatments, the researchers advise caution. More studies are urgently needed to find better solutions to help older patients with dementia who have agitation, aggression, and psychosis.
Additional Information
Please access these Web sites via the online version of this summary at
Alzheimer's Disease International is an umbrella organisation of organisations worldwide
The Alzheimer's Research Trust in the UK is a charity funding research to cure or prevent dementias
The US National Institutes of Aging has information on Alzheimer Disease in English and Spanish
Two governmental regulatory agencies—the Medicines and Healthcare Products Regulatory Agency in the UK and the Food and Drug Administration in the US—offer information about antipsychotics in people with dementia
PMCID: PMC2276521  PMID: 18384230
11.  Demographic, Neuropsychological and Functional Predictors of Rate of Longitudinal Cognitive Decline in Hispanic Older Adults 
The identification of older adults who are at increased risk of future cognitive decline is often difficult, particularly in individuals of an ethnic minority. This study evaluated which baseline demographic, neuropsychological and functional variables were most strongly associated with future longitudinal decline in global cognitive function.
Participants were part of a community-based prospective longitudinal study of 1789 older Hispanics (Sacramento Area Latino Study on Aging (SALSA)).
A subsample of 639 individuals were evaluated, comprising cognitively normal, mildly impaired, and dementia cases, and were followed longitudinally for up to seven years. Sixty-three percent were tested in Spanish.
Latent growth curve modeling of longitudinal data was used to assess the effects of age, gender, education, language of test administration (Spanish or English), acculturation, baseline measures of neuropsychological function (i.e. verbal memory and confrontation naming) and baseline everyday functioning (as measured by the IQCODE) on rate of change in global cognitive impairment (measured by the 3MS).
Less education, being tested in English, and poorer scores on the neuropsychological tests were all cross-sectionally associated with lower baseline 3MS scores. However, longitudinal decline in global cognition over time was primarily associated with older age and poorer everyday function at baseline.
Informant-based ratings of functional impairment, which are easy to collect in a clinical setting, have significant utility in identifying Hispanic older adults at increased risk for future cognitive decline.
PMCID: PMC3200310  PMID: 20808135
Cognitive decline; Hispanic population
12.  Ginkgo biloba for Preventing Cognitive Decline in Older Adults 
The herbal product Ginkgo biloba is taken frequently with the intention of improving cognitive health in aging. However, evidence from adequately powered clinical trials is lacking regarding its effect on long-term cognitive functioning.
To determine whether G biloba slows the rates of global or domain-specific cognitive decline in older adults.
Design, Setting, and Participants
The Ginkgo Evaluation of Memory (GEM) study, a randomized, double-blind, placebo-controlled clinical trial of 3069 community-dwelling participants aged 72 to 96 years, conducted in 6 academic medical centers in the United States between 2000 and 2008, with a median follow-up of 6.1 years.
Twice-daily dose of 120-mg extract of G biloba (n=1545) or identical-appearing placebo (n=1524).
Main Outcome Measures
Rates of change over time in the Modified Mini-Mental State Examination (3MSE), in the cognitive subscale of the Alzheimer Disease Assessment Scale (ADAS-Cog), and in neuropsychological domains of memory, attention, visual-spatial construction, language, and executive functions, based on sums of z scores of individual tests.
Annual rates of decline in z scores did not differ between G biloba and placebo groups in any domains, including memory (0.043; 95% confidence interval [CI], 0.034-0.051 vs 0.041; 95% CI, 0.032-0.050), attention (0.043; 95% CI, 0.037-0.050 vs 0.048; 95% CI, 0.041-0.054), visuospatial abilities (0.107; 95% CI, 0.097-0.117 vs 0.118; 95% CI, 0.108-0.128), language (0.045; 95% CI, 0.037-0.054 vs 0.041; 95% CI, 0.033-0.048), and executive functions (0.092; 95% CI, 0.086-0.099 vs 0.089; 95% CI, 0.082-0.096). For the 3MSE and ADAS-Cog, rates of change varied by baseline cognitive status (mild cognitive impairment), but there were no differences in rates of change between treatment groups (for 3MSE, P=.71; for ADAS-Cog, P=.97). There was no significant effect modification of treatment on rate of decline by age, sex, race, education, APOE*E4 allele, or baseline mild cognitive impairment (P>.05).
Compared with placebo, the use of G biloba, 120 mg twice daily, did not result in less cognitive decline in older adults with normal cognition or with mild cognitive impairment.
Trial Registration Identifier: NCT00010803
PMCID: PMC2832285  PMID: 20040554
13.  Practice effects in the prediction of long-term cognitive outcome in three patient samples: A novel prognostic index 
Practice effects, defined as improvements in cognitive test performance due to repeated exposure to the test materials, have traditionally been viewed as sources of error. However, they might provide useful information for predicting cognitive outcome. The current study used three separate patient samples (older adults with mild cognitive impairments, individuals who were HIV +, individuals with Huntington’s disease) to examine the relationship between practice effects and cognitive functioning at a later point. Across all three samples, practice effects accounted for as much as 31 to 83% of the variance in the follow-up cognitive scores, after controlling for baseline cognitive functioning. If these findings can be replicated in other patients with neurodegenerative disorders, clinicians and researchers may be able to develop predictive models to identify the individuals who are most likely to demonstrate continued cognitive decline across time. The ability to utilize practice effects data would add a simple, convenient, and non-invasive marker for monitoring an individual patient’s cognitive status. Additionally, this prognostic index could be used to offer interventions to patients who are in the earliest stages of progressive neurodegenerative disorders.
PMCID: PMC1847360  PMID: 17142007
practice effects; cognitive outcome; Mild Cognitive Impairment; HIV; Huntington’s disease
14.  Physical Predictors of Cognitive Performance in Healthy Older Adults: A Cross-Sectional Analysis 
PLoS ONE  2013;8(7):e70799.
There is ample evidence that physical and cognitive performance are related, but the results of studies investigating this relationship show great variability. Both physical performance and cognitive performance are constructs consisting of several subdomains, but it is presently unknown if the relationship between physical and cognitive performance depends on subdomain of either construct and whether gender and age moderate this relationship. The aim of this study is to identify the strongest physical predictors of cognitive performance, to determine the specificity of these predictors for various cognitive subdomains, and to examine gender and age as potential moderators of the relationship between physical and cognitive performance in a sample of community-dwelling older adults. In total, 98 men and 122 women (average age 74.0±5.6 years) were subjected to a series of performance-based physical fitness and neuropsychological tests. Muscle strength, balance, functional reach, and walking ability (combined score of walking speed and endurance) were considered to predict cognitive performance across several domains (i.e. memory, verbal attention, visual attention, set-shifting, visuo-motor attention, inhibition and intelligence). Results showed that muscle strength was a significant predictor of cognitive performance for men and women. Walking ability and balance were significant predictors of cognitive performance for men, whereas only walking ability was significant for women. We did not find a moderating effect of age, nor did we find support for a differential effect of the physical predictors across different cognitive subdomains. In summary, our results showed a significant relationship between cognitive and physical performance, with a moderating effect of gender.
PMCID: PMC3728317  PMID: 23936251
15.  Feasibility of Predicting MCI/AD Using Neuropsychological Tests and Serum β-Amyloid 
We examined the usefulness of brief neuropsychological tests and serum Aβ as a predictive test for detecting MCI/AD in older adults. Serum Aβ levels were measured from 208 subjects who were cognitively normal at enrollment and blood draw. Twenty-eight of the subjects subsequently developed MCI (n = 18) or AD (n = 10) over the follow-up period. Baseline measures of global cognition, memory, language fluency, and serum Aβ1–42 and the ratio of serum Aβ1–42/Aβ1–40 were significant predictors for future MCI/AD using Cox regression with demographic variables, APOE ε4, vascular risk factors, and specific medication as covariates. An optimal sensitivity of 85.2% and specificity of 86.5% for predicting MCI/AD was achieved using ROC analyses. Brief neuropsychological tests and measurements of Aβ1–42 obtained via blood warrants further study as a practical and cost effective method for wide-scale screening for identifying older adults who may be at-risk for pathological cognitive decline.
PMCID: PMC3109876  PMID: 21660215
16.  The Memory and Aging Telephone Screen (MATS): Development and preliminary validation 
Telephone interviews are widely used in geriatric settings to identify eligible research participants and to perform brief follow-up assessments of cognition. This article reports on the development and validation of the Memory and Aging Telephone Screen (MATS), a structured interview for older adults with mild cognitive impairment and/or significant memory complaints. We also developed three alternate forms of the MATS objective memory test to reduce practice effects engendered by multiple administrations.
Participants were enrolled in a longitudinal study that included 120 older adults with amnestic mild cognitive impairment (MCI), subjective cognitive complaints (CC) but without deficit on neuropsychological tests, and demographically-matched healthy controls (HC). An additional 15 patients with mild probable Alzheimer's disease (AD) completed the alternative forms study. All participants received the original MATS version, and a subset (n = 90) later received two of three alternate forms.
The MATS was sensitive to group differences and the alternate forms were equivalent. MATS objective memory test scores showed adequate stability over one year and were moderately correlated with scores on a widely used list-learning test (CVLT-II).
The MATS, a repeatable telephone screen that includes objective and subjective memory assessments, is useful for detecting individuals in the preclinical and early stages of dementia. Results encourage use of the MATS as a reliable and valid cognitive screening tool in research and clinical settings. Longitudinal assessments are being performed to investigate the predictive validity of the MATS for cognitive progression in MCI.
PMCID: PMC2712946  PMID: 19595923
telephone screen; mild cognitive impairment; cognitive complaints; neuropsychological assessment; interview; memory
17.  Psychometric properties of the Late-Life Function and Disability Instrument: a systematic review 
BMC Geriatrics  2014;14:12.
The choice of measure for use as a primary outcome in geriatric research is contingent upon the construct of interest and evidence for its psychometric properties. The Late-Life Function and Disability Instrument (LLFDI) has been widely used to assess functional limitations and disability in studies with older adults. The primary aim of this systematic review was to evaluate the current available evidence for the psychometric properties of the LLFDI.
Published studies of any design reporting results based on administration of the original version of the LLFDI in community-dwelling older adults were identified after searches of 9 electronic databases. Data related to construct validity (convergent/divergent and known-groups validity), test-retest reliability and sensitivity to change were extracted. Effect sizes were calculated for within-group changes and summarized graphically.
Seventy-one studies including 17,301 older adults met inclusion criteria. Data supporting the convergent/divergent and known-groups validity for both the Function and Disability components were extracted from 30 and 18 studies, respectively. High test-retest reliability was found for the Function component, while results for the Disability component were more variable. Sensitivity to change of the LLFDI was confirmed based on findings from 25 studies. The basic lower extremity subscale and overall summary score of the Function component and limitation dimension of the Disability component were associated with the strongest relative effect sizes.
There is extensive evidence to support the construct validity and sensitivity to change of the LLFDI among various clinical populations of community-dwelling older adults. Further work is needed on predictive validity and values for clinically important change. Findings from this review can be used to guide the selection of the most appropriate LLFDI subscale for use an outcome measure in geriatric research and practice.
PMCID: PMC3909447  PMID: 24476510
Function; Disability; Psychometric properties; Community-dwelling older adults
18.  The Alzheimer’s Prevention Initiative composite cognitive test score: Sample size estimates for the evaluation of preclinical Alzheimer’s disease treatments in presenilin 1 E280A mutation carriers 
There is a need to identify a cognitive composite that is sensitive to tracking preclinical AD decline to be used as a primary endpoint in treatment trials.
We capitalized on longitudinal data, collected from 1995 to 2010, from cognitively unimpaired presenilin 1 (PSEN1) E280A mutation carriers from the world’s largest known early-onset autosomal dominant AD (ADAD) kindred to identify a composite cognitive test with the greatest statistical power to track preclinical AD decline and estimate the number of carriers age 30 and older needed to detect a treatment effect in the Alzheimer’s Prevention Initiative’s (API) preclinical AD treatment trial. The mean-to-standard-deviation ratios (MSDRs) of change over time were calculated in a search for the optimal combination of one to seven cognitive tests/sub-tests drawn from the neuropsychological test battery in cognitively unimpaired mutation carriers during a two and five year follow-up period, using data from non-carriers during the same time period to correct for aging and practice effects. Combinations that performed well were then evaluated for robustness across follow-up years, occurrence of selected items within top performing combinations and representation of relevant cognitive domains.
This optimal test combination included CERAD Word List Recall, CERAD Boston Naming Test (high frequency items), MMSE Orientation to Time, CERAD Constructional Praxis and Ravens Progressive Matrices (Set A) with an MSDR of 1.62. This composite is more sensitive than using either the CERAD Word List Recall (MSDR=0.38) or the entire CERAD-Col battery (MSDR=0.76). A sample size of 75 cognitively normal PSEN1-E280A mutation carriers age 30 and older per treatment arm allows for a detectable treatment effect of 29% in a 60-month trial (80% power, p=0.05).
We have identified a composite cognitive test score representing multiple cognitive domains that has improved power compared to the most sensitive single test item to track preclinical AD decline in ADAD mutation carriers and evaluate preclinical AD treatments. This API composite cognitive test score will be used as the primary endpoint in the first API trial in cognitively unimpaired ADAD carriers within 15 years of their estimated age at clinical onset. We have independently confirmed our findings in a separate cohort of cognitively healthy older adults who progressed to the clinical stages of late-onset AD, described in a separate report, and continue to refine the composite in independent cohorts and compared with other analytical approaches.
PMCID: PMC4331113  PMID: 24816373
composite cognitive score; API; Alzheimer’s Prevention Initiative; E280A; PSEN1; presenilin1; sample size; preclinical; cognitively unimpaired; autosomal dominant; ADAD
19.  Performance on the Clock-in-the-Box in elders: normative performance, comparison to cognitive tests, and relationship to functional performance 
The American journal of medicine  2011;124(7):662-669.
The Clock-in-the-Box is a rapid (2 minute) cognitive screening tool. The purpose of this study was a) to compare the Clock-in-the-Box with the Mini-Mental State Exam (MMSE) and neuropsychological tests, b) to determine Clock-in-the-Box score normative values by age and education group, and c) to determine if the Clock-in-the-Box score is associated with measures of physical function.
Community-dwelling older participants in the Boston-area were recruited for a prospective, longitudinal study in which they completed a variety of cognitive and functional assessments.
At baseline, participants (n=798; mean age (±SD)=78.2 (±5.5) years; 14 (±3) mean years of education) completed in-home assessments of cognition – the Clock-in-the-Box and MMSE; measures of independent function - Activities of Daily Living and Instrumental Activities of Daily Living; and measures of physical function - Short Physical Performance Battery. Mean MMSE score was 27.1 (±1.6; range 0–30 – 0 worst) and mean Clock-in-the-Box was 6.2 (±1.6; range 0–8 – 0 worst). Performance on the Clock-in-the-Box was correlated (Spearman) with the MMSE (r=0.49, p<.001) and neuropsychological measures (r=0.37–0.50; p<.001). Higher Clock-in-the-Box score was significantly associated with no difficulty in Activities of Daily Living (χ2=39.6, p=<.001) and Instrumental Activities of Daily Living (χ2=35.5, p=<.001). Additionally, higher Clock-in-the-Box scores were associated with higher scores on the Short Physical Performance Battery (F=5.4, p<.001).
The Clock-in-the-Box is a brief cognitive screening test that is correlated with the MMSE, neuropsychological tests, and measures of independent and physical function in community-dwelling older adults.
PMCID: PMC3128995  PMID: 21592451
cognition; aged; function; dementia; screening; neuropsychological testing
20.  Comparison of cognitive and UHDRS measures in monitoring disease progression in Huntington’s disease: a 12-month longitudinal study 
Progressive cognitive decline is a feature of Huntington’s disease (HD), an inherited neurodegenerative movement disorder. Comprehensive neuropsychological testing is the ‘gold standard’ to establish cognitive status but is often impractical in time-constrained clinics. The study evaluated the utility of brief cognitive tests (MMSE and MoCA), UHDRS measures and a comprehensive neuropsychological tests battery in monitoring short-term disease progression in HD. Twenty-two manifest HD patients and 22 matched controls were assessed at baseline and 12-month. A linear mixed-effect model showed that although the HD group had minimal change in overall global cognition after 12 months, they did show a significant decline relative to the control group. The controls exhibited a practice effect in most of the cognitive domain scores over time. Cognitive decline at 12-month in HD was found in the executive function domain but the effect of this on global cognitive score was masked by the improvement in their language domain score. The varying practice effects by cognitive domain with repeated testing indicates the importance of comparing HD patients to control group in research trials and that cognitive progression over 12 months in HD should not be judged by changes in global cognitive score. The three brief cognitive tests effectively described cognition of HD patients on cross-sectional analysis. The UHDRS cognitive component, which focuses on testing executive function and had low variance over time, is a more reliable brief substitute for comprehensive neuropsychological testing than MMSE and MoCA in monitoring cognitive changes in HD patients after 12 months.
PMCID: PMC4105864  PMID: 25053996
Huntington’s disease; Disease progression; Cognition; UHDRS; Longitudinal
21.  Study of Mental Activity and Regular Training (SMART) in at risk individuals: A randomised double blind, sham controlled, longitudinal trial 
BMC Geriatrics  2011;11:19.
The extent to which mental and physical exercise may slow cognitive decline in adults with early signs of cognitive impairment is unknown. This article provides the rationale and methodology of the first trial to investigate the isolated and combined effects of cognitive training (CT) and progressive resistance training (PRT) on general cognitive function and functional independence in older adults with early cognitive impairment: Study of Mental and Regular Training (SMART). Our secondary aim is to quantify the differential adaptations to these interventions in terms of brain morphology and function, cardiovascular and metabolic function, exercise capacity, psychological state and body composition, to identify the potential mechanisms of benefit and broader health status effects.
SMART is a double-blind randomized, double sham-controlled trial. One hundred and thirty-two community-dwelling volunteers will be recruited. Primary inclusion criteria are: at risk for cognitive decline as defined by neuropsychology assessment, low physical activity levels, stable disease, and age over 55 years. The two active interventions are computerized CT and whole body, high intensity PRT. The two sham interventions are educational videos and seated calisthenics. Participants are randomized into 1 of 4 supervised training groups (2 d/wk × 6 mo) in a fully factorial design. Primary outcomes measured at baseline, 6, and 18 months are the Alzheimer's Disease Assessment Scale (ADAS-Cog), neuropsychological test scores, and Bayer Informant Instrumental Activities of Daily Living (B-IADLs). Secondary outcomes are psychological well-being, quality of life, cardiovascular and musculoskeletal function, body composition, insulin resistance, systemic inflammation and anabolic/neurotrophic hormones, and brain morphology and function via Magnetic Resonance Imaging (MRI) and Spectroscopy (fMRS).
SMART will provide a novel evaluation of the immediate and long term benefits of CT, PRT, and combined CT and PRT on global cognitive function and brain morphology, as well as potential underlying mechanisms of adaptation in older adults at risk of further cognitive decline.
Trial Registration
Australia and New Zealand Clinical Trials Register (ANZCTR): ANZCTRN12608000489392
PMCID: PMC3110111  PMID: 21510896
22.  Practice Effect and Normative Data of an HIV-specific Neuropsychological Testing Battery among Healthy Thais 
A longitudinal cohort study was conducted in Bangkok, Thailand between 2008 and 2013 in order to determine the practice effect of serial neuropsychological testing and establish normative data among normal (HIV-uninfected) Thai volunteers.
Material and Method
The authors enrolled 511 cognitively healthy individuals (HIV-uninfected, no drug abuse or other previous/current neurological or psychological conditions) to assess baseline performance on a HIV-specific neuropsychological testing battery. Ninety-nine subjects were re-assessed at 6 and 12 months to evaluate practice effects.
The mean age of the 99 subjects completing longitudinal visits was 49.2 years and 53 were male. The authors identified improved mean raw scores on most neuropsychological tests with repeated measurements; however, only change in WHO Auditory Verbal Learning Test (AVLT) scores (learning, attention, immediate and delayed recall tasks) met statistical significance, with larger differences seen between baseline and 6-month compared to 6 and 12 months follow-up. Older age correlated with poorer baseline raw score, and was a predictor of worse performance at 6 months and 12 months on several tasks. Level of education was associated with practice effects on several tests. No similar effects were observed with gender.
The authors identified improved performance after repeated measurements revealing a significant practice effect on an HIV-specific neuropsychological testing battery employed in Bangkok, Thailand. Main predictors were age and educational attainment.
PMCID: PMC4324973  PMID: 25518198
Thailand; neuropsychological test; cognition
23.  The LIFE Cognition Study: design and baseline characteristics 
Observational studies have shown beneficial relationships between exercise and cognitive function. Some clinical trials have also demonstrated improvements in cognitive function in response to moderate–high intensity aerobic exercise; however, these have been limited by relatively small sample sizes and short durations. The Lifestyle Interventions and Independence for Elders (LIFE) Study is the largest and longest randomized controlled clinical trial of physical activity with cognitive outcomes, in older sedentary adults at increased risk for incident mobility disability. One LIFE Study objective is to evaluate the effects of a structured physical activity program on changes in cognitive function and incident all-cause mild cognitive impairment or dementia. Here, we present the design and baseline cognitive data. At baseline, participants completed the modified Mini Mental Status Examination, Hopkins Verbal Learning Test, Digit Symbol Coding, Modified Rey–Osterrieth Complex Figure, and a computerized battery, selected to be sensitive to changes in speed of processing and executive functioning. During follow up, participants completed the same battery, along with the Category Fluency for Animals, Boston Naming, and Trail Making tests. The description of the mild cognitive impairment/dementia adjudication process is presented here. Participants with worse baseline Short Physical Performance Battery scores (prespecified at ≤7) had significantly lower median cognitive test scores compared with those having scores of 8 or 9 with modified Mini Mental Status Examination score of 91 versus (vs) 93, Hopkins Verbal Learning Test delayed recall score of 7.4 vs 7.9, and Digit Symbol Coding score of 45 vs 48, respectively (all P<0.001). The LIFE Study will contribute important information on the effects of a structured physical activity program on cognitive outcomes in sedentary older adults at particular risk for mobility impairment. In addition to its importance in the area of prevention of cognitive decline, the LIFE Study will also likely serve as a model for exercise and other behavioral intervention trials in older adults.
PMCID: PMC4154884  PMID: 25210447
exercise; physical activity; older adults; dementia
24.  Cognitive Functioning Predicts Driver Safety On Road-Tests 1 and 2 Years Later 
Our ability to predict aging related declines in driving performance from off-road assessments have clinical practice and social policy implications.
1) To describe longitudinal changes in mean-level and evaluate rank-order stability in potential predictors of driving safety (visual sensory, motor, visual attention, and cognitive functioning) and safety errors during an 18-mile on-road-drive-test among older adults. 2) To evaluate the relative predictive power of earlier visual sensory, motor, visual attention, and cognitive functioning on future safety errors controlling for earlier driving capacity.
A three-year longitudinal observational study;
A large teaching hospital in the Mid-West;
111 neurologically normal older adults (60 to 89 years at baseline);
Safety errors based on video review of a standard 18-mile on-road driving test served as the outcome measure. Comprehensive battery of tests on the predictor side included visual sensory functioning, motor functioning, cognitive functioning, and a measure of Useful Field of View.
Longitudinal changes in mean-levels of safety errors and cognitive functioning were small from year-to-year. Relative rank-order stability between consecutive assessments was moderate in overall safety errors, it was moderate to strong in visual attention and cognitive functioning. While prospective bivariate correlations ranged from fair to moderate between safety errors and predictors, only functioning in the cognitive domain predicted future driver performance one and two-years later in multivariate analyses.
Normative aging related declines in driver performance as assessed by on-road tests emerge slowly. The findings clearly demonstrated that even in the presence conservative controls, such as previous driving ability, age, visual sensory and motor functioning, cognitive functioning predicted future driving performance on-road one and two-years later.
PMCID: PMC3258369  PMID: 22091535
neuropsychological tests; safety errors; cognitive decline; instrumented vehicle
25.  Predicting Alzheimer's Disease: Neuropsychological Tests, Self Reports, and Informant Reports of Cognitive Difficulties 
Despite the strong need for evidence-based diagnostics, there is disagreement about the cognitive tools that best predict incident Alzheimer's disease (AD) in nondemented elders. We investigated the independent and combined contributions to the risk of AD of three key domains of cognitive assessment: neuropsychological measurement, self reports, and informant reports.
Longitudinal, community-based sample.
Einstein Aging Study.
Six hundred twenty-seven non-demented older adults aged 70 and above systematically recruited from the Bronx, NY.
Comprehensive assessment included neurological exam, behavioral questions, and neuropsychological testing. AD diagnoses were based on DSM-IV criteria assigned at a multidisciplinary consensus case conference. The major statistical analyses utilized Cox proportional hazards models (with age as the time scale), adjusted for gender, education, and depressive symptoms.
Forty-eight participants developed incident AD during a median of 3.3 years of follow-up. Self and informant reports of cognitive status as well as baseline scores on tests of episodic memory and psychomotor speed predicted the onset of AD. In models examining all the variables simultaneously, however, only the episodic memory tests and informant reports were associated with risk of AD. A likelihood ratio test confirmed the incremental effect of informant reports in addition to the neuropsychological test scores (P=0.035).
Informant ratings improved the prediction of AD conversion above and beyond objective memory impairment in non-demented elders. Combining these cognitive measures may provide a useful, empirical method for identifying individuals at high risk for future AD.
PMCID: PMC3375855  PMID: 22690986
Cognitive complaints; Subjective memory complaints; Informant reports; AD prediction; Neuropsychological tests

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