Cognitively Impaired Not Demented Research Articles

Parameterizing Practice in a Longitudinal Measurement Burst Design to Dissociate Retest Effects From Developmental Change: Implications for Aging Neuroscience.

Background: In longitudinal designs, the extraneous influence of retest effects can confound and obscure estimates of developmental change. The current study provides a novel approach to independently parameterize short-term retest effects and long-term developmental change estimates by leveraging a measurement burst design and three-level multilevel modeling. We further employ these short- and long-term slopes as predictors of cognitive status at long-term follow-up assessments.Methods: Participants included 304 older adults from Project MIND: a longitudinal measurement burst study assessing cognitive performance across both biweekly sessions and annual retests. Participants were classified as either Healthy controls (HC) or Cognitively Impaired, not Demented (CIND) at baseline, the final burst assessment (Year 4), and at an additional four-year follow-up (Year 8). Response time inconsistencies (RTI) were computed at each burst occasion for a simple choice response time (CRT) task and a one-back response time (BRT) task. Three-level multilevel models were employed to simultaneously examine change in RTI for both CRT and BRT across weeks within years, as well as across years, in order to dissociate within-individual retest effects (short-term) from developmental (long-term) change slopes. Individual slopes were then extracted and utilized in a series of multinomial logistic regression equations to contrast short- vs. long-term RTI change as predictors of cognitive status.Results: Separately parameterizing short- and long-term change estimates yielded distinct patterns of variation. CRT RTI remained stable across short-term weekly assessments, while significantly increasing across years. In contrast, BRT RTI decreased significantly across short-term assessments but showed no change across long-term assessments. After dissociating change estimates, short-term BRT as well as long-term CRT and BRT estimates predicted cognitive status at long-term follow-ups; increases in RTI, suggesting either an inability to benefit from retest or process-based developmental decline, were associated with an increased likelihood of being classified as CIND.Conclusions: We showcase an innovative approach to dissociate retest effects from developmental change across and within individuals. Accurately parameterizing these distinct change estimates can both reduce systematic bias in longitudinal trend estimates as well as provide a clinically useful tool by utilizing retest effects to predict cognitive health and impairment.

Apolipoprotein E4‐driven effects on inflammatory and neurotrophic factors in peripheral extracellular vesicles from cognitively impaired not demented participants converted to Alzheimer’s disease

AbstractBackgroundIn brain, extracellular vesicles (EVs) play an essential role in neuron‐glia interface and ensure the crosstalk between the brain and the periphery. Only a few studies have demonstrated the apolipoprotein E4 variant (APOE ε4)‐driven dysfunction of EVs pathway and the risk to develop Alzheimer’s disease (AD). To better understand the role of APOE ε4 in pre‐clinical AD, we determined levels of pathogenic, neurotrophic and inflammatory proteins in peripheral EVs (pEVs) and in plasma from cognitively impaired‐not demented (CIND) participants stratified upon the absence (APOE ε4‐) or the presence (APOE ε4+) of the ε4 allele of APOE.MethodLevels of 15 neurodegenerative, neurotrophic and neuroinflammatory proteins were quantified in pEVs by the multiplex Luminex assay and compared to their plasma levels from cognitively normal and CIND participantsResultFor the first time, several neurotrophic and inflammatory markers including LCN‐2, S100B, ANGPTL‐4, NPTX‐2 and α‐synuclein were evidenced in pEVs. Some proteins such as α‐Syn, NPTX‐2 and S100B were enriched in pEVs as compared to plasma. APOE ε4+ was associated with differential regulation of 7 markers and compromised the release of pEVs formed by an endosomal route. The pentraxin‐2/α‐synuclein ratio measured in pEVs was able to predict AD 5 years before the onset among APOE ε4+ CIND individuals. Discussion: Our findings suggest an alteration of the endosomal pathway in APOE ε4+ carriers and that pEVs pentraxin‐2/α‐synuclein ratio could serve as a useful early biomarker for AD susceptibility.ConclusionThe findings reported herein provide a comprehensive insight and enhance our knowledge on the emerging role of ApoE4 in abnormal pEVs cargo proteins processing and the identification of blood‐based biomarkers.

Effect of APOE ε4 allele on levels of apolipoproteins E, J, and D, and redox signature in circulating extracellular vesicles from cognitively impaired with no dementia participants converted to Alzheimer's disease.

IntroductionThe substantial link between apolipoprotein E (APOE) ε4 allele and oxidative stress may underlie enhanced Alzheimer's disease (AD) risk. Here, we studied the impact of APOE ε4 on the level of apolipoproteins with antioxidant activities along with oxidative markers in circulating extracellular vesicles (cEVs) and plasma from cognitively impaired‐not demented (CIND) individuals converted to AD (CIND‐AD).MethodsApolipoproteins E, J, and D and antioxidant response markers were determined in cEVs and plasma using immunoblotting, electrochemical examination, and spectrofluorimetry.ResultsTotal antioxidant capacity and apolipoprotein D levels in cEVs, as judged by regression analysis and cognitive performance correlations, allowed us to differentiate CIND APOE ε4 carriers from controls and to predict their progression to AD 5 years later.DiscussionOur findings support the pathological redox linkage between APOE ε4 and AD onset and suggest the use of cEVs oxidative signature in early AD diagnosis.

Longitudinal changes in response time mean and inconsistency exhibit predictive dissociations for risk of cognitive impairment.

Although mean response time (RT) is a commonly used indicator of cognitive function, trial-to-trial variability (RT inconsistency [RTI]) represents a dissociable dimension of performance arguably more sensitive for characterizing cognitive status. The present study explores whether (a) RT mean or inconsistency reflects a more dispositional characteristic of an individual, particularly with increased cognitive impairment; (b) RT mean and inconsistency exhibit comparable patterns of change across a 4-year period; and (c) these rates of change differentially predict cognitive status. A sample of 304 adults (64-92 years) at baseline completed a choice RT task weekly for 4-5 weeks, repeating this protocol and a basic neuropsychological assessment annually for 4 years. Three cognitive status subgroups were identified at baseline and Year 4: healthy controls (HCs), as well as cognitively impaired-not-demented (CIND) status based upon single (CIND-S) and multiple (CIND-M) domains. RTI was disproportionately stable among cognitively compromised individuals at baseline, suggesting that increased RTI is a dispositional characteristic reflecting underlying changes in psychological process or neurological function. Notably, 4-year trajectories of change for RT mean versus RTI were dissociable; whereas the HC and CIND-S groups exhibited faster mean RTs over time, CIND-M individuals exhibited significant RTI increases. Multinomial logistic regressions demonstrated that greater RTI at baseline (OR = 2.58, p < .01) and steeper 4-year increases (OR = 4.40, p < .01) were linked to increased likelihood of CIND-M classification at Year 4, independent of age, education, chronic health conditions, and mean RT. RT mean and RTI confer distinct sources of information about cognitive function and status. Overall, RTI holds promise as an early indicator of normal and pathological cognitive aging. (PsycINFO Database Record (c) 2020 APA, all rights reserved).

Abstract TP187: 24-hour Ambulatory Blood Pressure, Cognitive Performance, and Cerebral Microbleeds in the Elderly

Introduction: Multiple studies suggest a role for blood pressure (BP) variability and nocturnal BP dipping in the development of cerebrovascular disease and cognitive impairment. We analyzed cross-sectional data from a cohort of 90+ year-olds to test the hypothesis that BP variables are associated with cognitive function and cerebral microbleeds (CMB). Methods: Study subjects were 121 participants (mean age = 93 years, 63% female) in The 90+ Study , a study of aging in individuals aged 90 years and older from a California retirement community. Participants were given a neuropsychological test battery to determine cognitive status. All subjects underwent 24-hour ambulatory BP measurement with a automatic device. MRI scans were available for 26 participants. Over three time frames (24-hour, daytime, nighttime) and separately for SBP and DBP, we represented BP by mean, minimum, maximum, standard deviation (SD), coefficient of variation, average real variability, percentage of high measurements (≥140 mmHg for SBP and ≥90 mmHg for DBP), percentage of low measurements (&lt;90 mmHg for SBP and &lt;60 mmHg for DBP), and nocturnal dip (% change of mean night BP from mean day BP). Differences in means of BP variables between groups based on cognitive status (normal vs cognitively impaired not demented (CIND)/demented) and presence/absence of CMB were tested using t-tests. Results: Cognitive status was normal in 97 subjects, CIND/demented in 24. Mean nocturnal dips (both SBP and DBP) differed significantly between the two groups, with normal participants having on average greater dip levels (6.6 vs 1.3, p=0.006 for SBP and 11 vs 4.4, p=0.002 for DBP). No other BP variable showed a large or significant difference. Greater nocturnal dips were also related to better performance on cognitive test scores related to language, recent memory, and visual-spatial ability. MRI findings showed subjects with CMB (n=18) had higher SD of daytime SBP than those without (n=8) (20 vs 16, p=0.03). Those with CMB also had a greater proportion of high nighttime DBP (≥90 mmHg) readings (3.6 vs 0, p=0.03). Conclusions: Among 90+ year olds, altered nocturnal BP dipping may have a role in cognitive impairment, while SBP variation and diastolic hypertension may contribute to development of microbleeds.

Cognitively-Impaired-Not-Demented Status Moderates the Time-Varying Association between Finger Tapping Inconsistency and Executive Performance.

Response time inconsistency (RTI) in cognitive performance predicts deleterious health outcomes in late-life; however, RTI estimates are often confounded by additional influences (e.g., individual differences in learning). Finger tapping is a basic sensorimotor measure largely independent of higher-order cognition that may circumvent such confounds of RTI estimates. We examined the within-person coupling of finger-tapping mean and RTI on working memory, and the moderation of these associations by cognitive status. A total of 262 older adults were recruited and classified as controls, cognitively-impaired-not-demented (CIND) unstable or CIND stable. Participants completed finger-tapping and working-memory tasks during multiple weekly assessments, repeated annually for 4 years. Within-person coupling estimates from multilevel models indicated that on occasions when RTI was greater, working-memory response latency was slower for the CIND-stable, but not for the CIND-unstable or control individuals. The finger-tapping task shows potential for minimizing confounds on RTI estimates, and for yielding RTI estimates sensitive to central nervous system function and cognitive status.

Computer Tomography for Prediction of Cognitive Outcomes after Ischemic Cerebrovascular Events

The aim of this study was to evaluate whether parameters noted on a single, acute computed tomographic (CT) scan, are associated with significant cognitive impairment (SCogI), and can help in the prediction of SCogI 3-6months afterstroke or transient ischemic attack (TIA). Patients with a recent (≤14days) ischemic stroke or TIA, without preexisting dementia, underwent noncontrast CT scan within 24hours of admission. A formal neuropsychologic battery was administered 3-6months from index stroke. SCogI was defined as moderate cognitively impaired, not demented (CIND) (≥3 domains impaired), and dementia diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders, Fourth Edition, criteria. Logistic regression models were used to examine associations between CT parameters and SCogI. Receiver operating characteristic analysis with an area under the curve (AUC) was performed to assess discriminatory ability of radiological parameters for SCogI. In all, 318 patients were included: 250 (78.6 %) with ischemic stroke and 68 (21.4%) with TIA; the mean age was 59.8 (±11.4) years. At 3-6months, 76 (23.9 %) had SCogI (67 CIND moderate and 9 dementia). The presence of significant atrophy (P=.02) and chronic infarcts (P=.03) were associated with SCogI at 3-6months. A significant increase in AUC was noted after addition of summarized CT results to a clinical score derived from age and baseline Montreal Cognitive Assessment (cutoff 21 of 22) for detection of SCogI: .83 (.78-.89) to .86 (.82-.91); P=.03. CT parameters are independently associated with SCogI at 3-6months after an ischemic cerebrovascular event and may be a clinically useful component in predicting for SCogI after stroke.

Apolipoprotein E gene, environmental risk factors, and their interactions in dementia among seniors

Little research has been conducted to explore the joint effect of apolipoprotein E (ApoE) genotypes and environmental risk factors on dementia. In this study, we examined the roles of ApoE alleles and genotypes in dementia and cognitively impaired not demented (CIND), assessed the risk of co-existing or prior health conditions (i.e. depression), family history of diseases, and lifestyle factors on dementia, and explored the interactions between genetic and environmental risk factors and their joint effects on dementia and cognitive impairment. This is a genetic association study. A total of 1185 seniors (391 dementia, 389 CIND, and 405 cognitively intact, matched for age and gender) were selected from the Canadian Study of Health and Aging clinical assessment datasets. Multivariate logistic regression was used to explore the association between ApoE, environment risk factors, and outcomes. Participants with ApoE ε4 alleles or ε3/ε4 genotypes were at risk of dementia. More education reduced the risk of dementia or CIND. Previous health conditions (e.g. stroke) increased the risk of dementia or CIND. Regular exercise decreased the risk of CIND. ApoE ε3/ε4 genotype and baseline depression had a 7.97-fold greater risk of incident dementia after adjusting for other significant risk factors. No interactions were found in any dementia and CIND models. More attention should be paid to assess and treat depressed older people, especially for those with ApoE ε3/ε4 genotypes. Further replication studies in different populations are warranted.

Neuropsychiatric Symptom Clusters and Functional Disability in Cognitively-Impaired-Not-Demented Individuals

Previous research has shown that cognitively-impaired-not-demented (CIND) individuals with at least one neuropsychiatric symptom (NPS) have more functional disability than individuals without any NPSs. The objectives of the present study were to determine whether there are consistent clusters of NPS in CIND individuals and whether certain NPS clusters are more strongly associated with measures of functional disability than other NPS clusters in this population. This was a cross-sectional baseline study of NPS using the Neuropsychiatric Inventory (NPI) in a national clinic-based observational cohort study (the Canadian Cohort Study of Cognitive Impairment and Related Dementias study). The present investigation focuses on a subset of CIND subjects (73%) whose informant endorsed the presence of at least one NPI item. A hierarchical cluster analysis identified two NPS clusters. One consisted of mood factors (i.e., depression, anxiety, apathy, irritability, and problems with sleep) and the other cluster captured frontal symptoms (i.e., aberrant motor behavior, disinhibition, agitation, and problems with appetite). NPSs grouped within the mood cluster were more common than the frontal cluster (95% of subjects had at least one NPS within the mood cluster versus 53% in the frontal cluster). However, the frontal cluster was more strongly associated with functional disability measures even after controlling for cognitive status (i.e., the Mini-Mental State Exam) and the mood cluster score. The frontal cluster of NPSs was more strongly associated with functional disability than the mood cluster.

Neuropsychological prediction of attrition due to death*

In aging research, attrition bias produces underestimates of cognitive decline and limits the interpretation of cognitive change. Using data from the Canadian Study of Health and Aging, we identified neuropsychological predictors of death among not cognitively impaired (NCI) and cognitively impaired, not-demented (CIND) persons. For those with NCI, two neuropsychological measures significantly predicted attrition, over and above age, in the short term, while age was the best long-term predictor. The absence of neuropsychological predictors for the CIND group may reflect the group's etiological heterogeneity. In future research, the use of a more homogeneous subset of CIND may yield additional predictors.

Dropouts and refusals in observational studies

The success of prevention trials of Alzheimer disease and other dementias (AD/dementia) hinges on their ability to recruit and retain at-risk study populations. Losing subjects is a threat to the power to detect a treatment effect and, potentially, to the validity of these studies. Observational cohort studies accumulate data around participant outcomes that can help to inform the design of future prevention trials. Our objectives were to investigate the rates of refusal and dropout within observational cohort studies and to evaluate their characteristics and impact. This study examined data from the Canadian Cohort Study of Cognitive Impairment and Related Dementias (ACCORD), a 2-year observational cohort study of patients newly referred to dementia clinics. The sample included 124 Not Cognitively Impaired (NCI) and 342 Cognitively Impaired Not Demented (CIND) subjects. Subjects who refused initial neuropsychological (NP) testing were compared to those who completed NP testing and subjects who dropped out to those who attended follow-up. Refusal was common, with 40% of subjects not completing neuropsychological testing at baseline. Dropout was also substantial, with 55% lost to the 2-year follow-up. Subjects who refused NP testing were significantly older and less educated. CIND refusers had lower cognitive and functional scores at entry and a 2-year progression rate to dementia twice as high as that of non-refusers. CIND dropouts also had lower baseline cognitive and functional scores. These observations suggest that dropouts and refusals in prevention trials include those subjects who are at high risk for progression to AD/dementia. Targeted strategies to retain these individuals within prevention studies will be needed to achieve sufficient study power and validity.

Outcomes of Cognitively Impaired Not Demented at 2 Years in the Canadian Cohort Study of Cognitive Impairment and Related Dementias

Background: People who are cognitively impaired not demented (CIND) can be at an increased risk for developing dementia, but little is known about the natural history of CIND in clinical settings. Method: We examined the 2-year outcome of CIND subjects in the Canadian Cohort Study of Cognitive Impairment and Related Dementias.CIND was diagnosed when at least one positive item was endorsed on the DSM-III-R dementia criteria, but not all criteria were met. CIND was further subclassified as: pre-Alzheimer’s disease (pre-AD), vascular cognitive impairment (VCI-ND), non-AD degenerative, psychiatric, other neurologic, other medical conditions, mixed disorders and no etiology identified (not otherwise specified [NOS]). Result: Of 146 CIND patients with 2-year follow-up data available, 49 (34%) progressed to dementia, while 20 (14%) recovered to not cognitively impaired (NCI). Progressors were significantly older than stable CIND and reverters (p < 0.0001; mean age = 71.1, 64.3, and 59.1, respectively), and there were significantly (p = 0.001) more ApoE Ε4 carriers among progressors (67%) than stable CIND (29%) and reverters (12%). Pre-AD CIND and VCI-ND had the highest rate of conversion to dementia (41.0 and 40.0%, respectively), while psychiatric CIND and CIND NOS had highest rate of recovery to NCI (20.0 and 30.0%, respectively). All conversions in pre-AD CIND were to ‘probable AD’. Conclusion: CIND consists of a heterogeneous group of disorders that can be classified syndromically. Many subclassess – not just those with pre-AD CIND – are at high risk of progression to dementia, usually to Alzheimer’s disease.

P2-183: An evaluation of functional disability in mild cognitive impairment: Baseline impairment does not predict progression in the ACCORD study

Patients who are classified as Cognitively–Impaired–Not–Demented (CIND) are at significantly increased risk of progression to dementia. Changes in functional ability define the transition to Alzheimer Disease (AD). However, the most sensitive predictors and patterns of functional decline remain to be fully determined. To evaluate the utility of the Disability Assessment of Dementia (DAD) scale in predicting and characterizing the progression of CIND to AD. The DAD is an informant–based instrument that measures both Instrumental Activities of Daily Living (IADLs) and Basic Activities of Daily Living (BADLs). A cohort of CIND subjects (n=70) was followed for two years within the Canadian Cohort Study of Cognitive Impairment and Related Dementias (ACCORD), of whom 31% progressed to AD (CIND–AD) while 69% remained stable (CIND–Stable). A comparison of DAD scores at entry and at year–2 was conducted between the CIND–AD and CIND–Stable groups with analysis of covariance (ANCOVA) adjusted for age, sex and education. Logistic regression, adjusted for the same variables, was used to assess the predictive ability of the total DAD scores. At baseline, there were neither significant differences between the total DAD scores of the CIND–AD and CIND–Stable (94.1±7.6 % and 94.8±10.8 % respectively), nor the BADL and IADL sub–scores. The mean DAD total change scores at year–2 were −12.0±19.2% for the CIND–AD group and +0.4±8.9% for the CIND–Stable group (p=0.002). Similarly, the rate of decline in both BADLs and IADLs was significantly greater (p=0.015 and p=0.002 respectively) in CIND–AD than in the CIND–Stable group. The baseline DAD score did not contribute significantly to the prediction of progression to AD (OR 1.0, 95% C.I. 0.9–1.1). As expected, individuals progressing to AD showed a greater decline in their functional abilities; however, the DAD total score at entry did not predict progression to AD. We anticipate that an evaluation of higher social functioning is likely required to detect the earliest significant changes in function that may herald or predict progression to AD.

Characterizing neuropsychiatric symptoms in subjects referred to dementia clinics

To characterize the neuropsychiatric symptoms (NPS) of subjects classified as not cognitively impaired (NCI), cognitively impaired-not demented (CIND), and dementia. A Canadian Cohort Study of Cognitive Impairment and Related Dementias (ACCORD) is a longitudinal investigation of individuals referred to eight Canadian dementia centers for evaluation of cognitive impairment and neurobehavioral symptoms. Of the inception cohort of 804 subjects for whom the informant-based Neuropsychiatric Inventory (NPI) was completed at study entry, 35 were classified as NCI, 193 as CIND, and 576 as dementia. The three diagnostic groups were compared on each of the 12 NPI items. Within each diagnostic group, comparisons were also made between symptomatic (NPS+; total score > 1) and asymptomatic (NPS-; total score = 0) subjects on measures of general cognitive status and functional disability. A subset of the NCI and CIND individuals were also compared on a comprehensive neuropsychological test battery. There was at least one NPI item reported in 60% of subjects with NCI, 74% with CIND, and 89% with dementia. The item scores for delusions, hallucinations, agitation, apathy, disinhibition, aberrant motor behavior, and problems with appetite were greater in dementia subjects than in NCI or CIND. There were no significant differences between subjects with NCI and CIND on any NPI item. For each diagnostic group, NPS+ subjects were more impaired on functional but not neuropsychological measures. Across all levels of cognition, neuropsychiatric symptoms (NPS) are an important feature in individuals referred to dementia clinics. The current data suggest that NPS may precede cognitive deficits in individuals classified as not cognitively impaired and cognitively impaired-not demented.

Compliance with neuropsychological testing may lead to underestimation of decline in Cognitively-Impaired-Not-Demented (CIND) individuals

subjects aged 65 or older. In the present study subjects all were clinically evaluated at entry and at 5 years. The diagnoses of normal, CIND and dementia were made according to DSM-III-R criteria. Rates of progression were computed for IN and CO subjects and then stratified by age group ( 75 or 75), sex, education ( grade 12, grade 12) and initial Modified Mini-Mental Status Examination (3MS) ( 90 or 90). Chi-square tests were performed with significant findings based on p 0.05. Results: There were 322 subjects (63 IN, 259 CO) at baseline who were diagnosed as cognitively normal. Of these 66% remained normal after 5 years, 23% progressed to CIND and 11% to dementia. Compared to CO subjects, IN subjects had significantly higher rates of progression to CIND (27 vs. 22%) and to dementia (18 vs. 9%). For age and 3MS level, this effect was specific to age 75 years and 3MS 90. Conclusion: Elderly individuals living in institutions are identified to be at an increased risk of developing both cognitive impairment and dementia. This environmental factor may further assist the enrichment of RCT study samples and should raise awareness of the potential role of non-biological factors within prevention study designs.

Neuropsychological Subgroups of Cognitively-Impaired-Not-Demented (CIND) Individuals: Delineation, Reliability, and Predictive Validity

The objectives of the present investigation were to determine whether subgroups of Cognitively-Impaired-Not-Demented (CIND) individuals with distinct neuropsychological profiles exist in two independent samples, and whether subgroup membership is related to diagnostic outcome over periods of 2 to 5 years. A series of cluster analyses was performed on ipsative factor z-scores derived from principal component analyses. Five subgroups were identified in the Base Sample (n = 461): Verbal Dysfunction,Verbal/Visuospatial Dysfunction,Memory/Verbal Dysfunction,Memory Dysfunction, and Visuospatial Dysfunction. This five-cluster solution was replicated in an independent sample of CIND individuals (n = 166). The highest rates of conversion to dementia were observed in the Memory Dysfunction and Memory/Verbal Dysfunction subgroups. The Verbal Dysfunction subgroup was most likely to show improvement in cognitive status. The cognitive heterogeneity of the CIND condition must be taken into account in future research focusing on the early identification of dementia. The research described herein was conducted as part of a doctoral dissertation by the first author (K.R.P.). While conducting this research, the first author (K.R.P.) received support from a Doctoral Training Award jointly funded by the Alzheimer Society of Canada and the Canadian Institutes of Health Research and by a Postgraduate Scholarship funded by the Natural Sciences and Engineering Research Council of Canada. The CSHA was supported through the National Health Research and Development program grant # 6606-3954-MC[S]. The ACCORD study was supported through the MRC PMAC program grant # PA14197 awarded to H.F. We would like to express our sincerest gratitude to the participants and their families for their commitment to both the CSHA and ACCORD studies. We would also like to acknowledge the hard work performed by each centre that participated in each of these two studies.

Neuropsychological Characterization of Cognitively-Impaired-Not-Demented (CIND) Individuals: Clinical Comparison Data

The primary objective of the present investigation was to characterize the neuropsychological test performance of a large sample of clinic-referred individuals diagnosed as Cognitively-Impaired-Not-Demented(CIND). Participants classified as Not-Cognitively-Impaired(NCI;n = 68)differed from CIND individuals(n = 205)on a number of demographic, clinical, and neuropsychological measures. A backward stepwise logistic regression analysis revealed that measures of learning and memory, visuoconstruction abilities, and cognitive flexibility provided the best discrimination between NCI and CIND participants. Clinical comparison data for CIND participants were generated for various demographically defined groups. The amount of inter-test scatter(highest minus lowest sample-basedz-score)and the overall number of cognitive impairments(impairment being defined as performance equal to or greater than 1 standard deviation below the sample mean)in CIND individuals are reported. The results support the impression that CIND is a cognitively heterogeneous condition.