Objectives: Careful characterization of how functional decline co-evolves with cognitive decline in older adults has yet to be well described. Most models of neurodegenerative disease postulate that cognitive decline predates and potentially leads to declines in everyday functional abilities; however, there is mounting evidence that subtle decline in instrumental activities of daily living (IADLs) may be detectable in older individuals who are still cognitively normal. Methods: The present study examines how the relationship between change in cognition and change in IADLs are best characterized among older adults who participated in the ACTIVE trial. Neuropsychological and IADL data were analyzed for 2802 older adults who were cognitively normal at study baseline and followed for up to 10 years. Results: Findings demonstrate that subtle, self-perceived difficulties in performing IADLs preceded and predicted subsequent declines on cognitive tests of memory, reasoning, and speed of processing. Conclusions: Findings are consistent with a growing body of literature suggesting that subjective changes in everyday abilities can be associated with more precipitous decline on objective cognitive measures and the development of mild cognitive impairment and dementia. (JINS, 2018, 24, 104–112)

In 2006, the National Institute of Neurological Disorders and Stroke-Canadian Stroke Network (NINDS-CSN) Vascular Cognitive Impairment Harmonization Standards recommended a 5-Minute Protocol as a brief screening instrument for vascular cognitive impairment (VCI). We report demographically adjusted norms for the 5-Minute Protocol and its relation to other measures of cognitive function and cerebrovascular risk factors. We performed a cross-sectional analysis of 7199 stroke-free adults in the REasons for Geographic And Racial Differences in Stroke (REGARDS) study on the NINDS-CSN 5-Minute Protocol score. Total scores on the 5-Minute Protocol were inversely correlated with age and positively correlated with years of education, and performance on the Six-Item Screener, Word List Learning, and Animal Fluency (all p-values <.001). Higher cerebrovascular risk on the Framingham Stroke Risk Profile (FSRP) was associated with lower total 5-Minute Protocol scores (p <.001). The 5-Minute Protocol also differentiated between participants with and without confirmed stroke and with and without stroke symptom histories (p <.001). The NINDS-CSN 5-Minute Protocol is a brief, easily administered screening measure that is sensitive to cerebrovascular risk and offers a valid method of screening for cognitive impairment in populations at risk for VCI. (JINS, 2014, 20, 1–12)

Rates of mild cognitive impairment (MCI) have varied substantially, depending on the criteria used and the samples surveyed. The present investigation used a psychometric algorithm for identifying MCI and its stability to determine if low cognitive functioning was related to poorer longitudinal outcomes. The Advanced Cognitive Training of Independent and Vital Elders (ACTIVE) study is a multi-site longitudinal investigation of long-term effects of cognitive training with older adults. ACTIVE exclusion criteria eliminated participants at highest risk for dementia (i.e., Mini-Mental State Examination < 23). Using composite normative for sample- and training-corrected psychometric data, 8.07% of the sample had amnestic impairment, while 25.09% had a non-amnestic impairment at baseline. Poorer baseline functional scores were observed in those with impairment at the first visit, including a higher rate of attrition, depressive symptoms, and self-reported physical functioning. Participants were then classified based upon the stability of their classification. Those who were stably impaired over the 5-year interval had the worst functional outcomes (e.g., Instrumental Activities of Daily Living performance), and inconsistency in classification over time also appeared to be associated increased risk. These findings suggest that there is prognostic value in assessing and tracking cognition to assist in identifying the critical baseline features associated with poorer outcomes. (JINS, 2012, 18, 1–15)

Systematic cognitive training produces long-term improvement in cognitive function and less difficulty in performing activities of daily living. We examined whether cognitive training was associated with reduced rate of incident dementia. Participants were from the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) study (n = 2,802). Incident dementia was defined using a combination of interview- and performance-based methods. Survival analysis was used to determine if ACTIVE treatment affected the rate of incident dementia during 5 years of follow-up. A total of 189 participants met criteria for incident dementia. Baseline factors predictive of incident dementia were older age, male gender, African American race, fewer years of education, relationship other than married, no alcohol use, worse MMSE, worse SF-36 physical functioning, higher depressive symptomatology, diabetes, and stroke (all p < .05). A multivariable model with significant predictors of incident dementia and training group revealed that cognitive training was not associated with a lower rate of incident dementia. Cognitive training did not affect rates of incident dementia after 5 years of follow-up. Longer follow-up or enhanced training may be needed to fully explore the preventive capacity of cognitive training in forestalling onset of dementia. (JINS, 2012, 18, 1–9)

Background: The relationship between weight and dementia risk has not been investigated in populations with relatively low body mass index (BMI) such as the Yoruba. This study set out to achieve this objective using a prospective observational design.

Methods: The setting was Idikan Ward in Ibadan City, Nigeria. The participants were all aged 65 years or older and were enrolled in the Indianapolis-Ibadan Dementia Project. Repeated cognitive assessments and clinical evaluations were conducted to identify participants with dementia or MCI during 10 years of follow-up (mean duration: 5.97 years). BMI measures, information on alcohol, smoking history, cancer, hypertension, diabetes, heart attack, stroke and depression were collected at each follow-up evaluation. Mixed effect models adjusted for covariates were used to examine the differences in BMI among participants who developed dementia or MCI and those who remained cognitively normal during the follow-up.

Results: This analysis included 1559 participants who had no dementia at their first BMI measurements. There were 136 subjects with incident dementia, 255 with MCI and 1168 with normal cognition by the end of the study. The mean BMI at baseline was higher for female participants (22.31; SD = 4.39) than for male (21.09; SD = 3.61, p < 0.001). A significantly greater decline in BMI was found in those with either incident dementia (p < 0.001) or incident MCI (p < 0.001) compared to normal subjects.

Conclusion: Decline in BMI is associated with incident MCI and dementia in elderly Yoruba. This observation calls for close monitoring of weight loss in elderly individuals which may indicate future cognitive impairment for timely detection and tailored interventions.

Background: We evaluated the effects of cognitive training on self-rated health at 1, 2, 3, and 5 years post-baseline.

Methods: In the ACTIVE (Advanced Cognitive Training for Independent and Vital Elderly) randomized controlled trial, 2,802 older adults (≥65 years) were randomly assigned to memory, reasoning, speed of processing, or no-contact control intervention groups. Complete data were available for 1,804 (64%) of the 2,802 participants at five years. A propensity score model was adjusted for attrition bias. The self-rated health question was coded using the Diehr et al. (2001) transformation (E = 95/VG = 90/G = 80/F = 30/P = 15), and analyzed with change-score regression models.

Results: The speed of processing (vs. no-contact control) group had statistically significant improvements (or protective effects) on changes in self-rated health at the 2, 3 and 5 year follow-ups. The 5-year improvement was 2.8 points (p = 0.03). No significant differences were observed in the memory or reasoning groups at any time.

Conclusion: The speed of processing intervention significantly protected self-rated health in ACTIVE, with the average benefit equivalent to half the difference between excellent vs. very good health.

Background: Neuropsychological tests, including tests of language ability, are frequently used to differentiate normal from pathological cognitive aging. However, language can be particularly difficult to assess in a standardized manner in cross-cultural studies and in patients from different educational and cultural backgrounds. This study examined the effects of age, gender, education and race on performance of two language tests: the animal fluency task (AFT) and the Indiana University Token Test (IUTT). We report population-based normative data on these tests from two combined ethnically divergent, cognitively normal, representative population samples of older adults.

Methods: Participants aged ≥65 years from the Monongahela-Youghiogheny Healthy Aging Team (MYHAT) and from the Indianapolis Study of Health and Aging (ISHA) were selected based on (1) a Clinical Dementia Rating (CDR) score of 0; (2) non-missing baseline language test data; and (3) race self-reported as African-American or white. The combined sample (n = 1885) was 28.1% African-American. Multivariate ordinal logistic regression was used to model the effects of demographic characteristics on test scores.

Results: On both language tests, better performance was significantly associated with higher education, younger age, and white race. On the IUTT, better performance was also associated with female gender. We found no significant interactions between age and sex, and between race and education.

Conclusions: Age and education are more potent variables than are race and gender influencing performance on these language tests. Demographically stratified normative tables for these measures can be used to guide test interpretation and aid clinical diagnosis of impaired cognition.

Cognitive training improves mental abilities in older adults, but the trainability of persons with memory impairment is unclear. We conducted a subgroup analysis of subjects in the Advanced Cognitive Training for Independent and Vital Elderly (ACTIVE) trial to examine this issue. ACTIVE enrolled 2802 non-demented, community-dwelling adults aged 65 years and older and randomly assigned them to one of four groups: Memory training, reasoning training, speed-of-processing training, or no-contact control. For this study, participants were defined as memory-impaired if baseline Rey Auditory Verbal Learning Test (AVLT) sum recall score was 1.5 SD or more below predicted AVLT sum recall score from a regression-derived formula using age, education, ethnicity, and vocabulary from all subjects at baseline. Assessments were taken at baseline (BL), post-test, first annual (A1), and second annual (A2) follow-up. One hundred and ninety-three subjects were defined as memory-impaired and 2580 were memory-normal. Training gain as a function memory status (impaired vs. normal) was compared in a mixed effects model. Results indicated that memory-impaired participants failed to benefit from Memory training but did show normal training gains after reasoning and speed training. Memory function appears to mediate response to structured cognitive interventions in older adults. (JINS, 2007, 13, 953–960.)

Sensitive measures of neuropsychological function were adapted to a telephone administration format for use in a large survey of quality of life in breast cancer survivors (BCS). Healthy controls (HC) and BCS were recruited from the community and administered the same neuropsychological test battery on two occasions separated by 1 week. Subjects were randomly assigned to conditions, stratified by diagnosis: In-person at Time-1 and In-person at Time-2 (P-P); Telephone at Time-1 and Telephone at Time-2 (T-T); T-P; and P-T. Four cognitive (Rey Auditory Verbal Learning Test, Controlled Oral Word Association, Digit Span, Symbol Digit) and two self-report measures (Squire Memory Self-Report Scale, Center for Epidemiological Studies Depression Scale) were used. The 106 subjects were randomized (54 HC and 52 BCS). Test–retest reliabilities (intraclass correlations) did not differ significantly by condition across the cognitive or self-report measures and ranged from moderate to near perfect (r's .43–.93; p's < .05). Mean scores at Time-1, practice effects (Time-1 to Time-2), and standard errors of measurement were comparable between In-person and Telephone administration formats. Results suggest that memory, attention, information processing speed, verbal fluency, and self-report of mood and memory can be measured reliably and precisely over the telephone. (JINS, 2007, 13, 799–806.)

Background: This is a community-based longitudinal epidemiological comparative study of elderly African Americans in Indianapolis and elderly Yoruba in Ibadan, Nigeria.

Method: A two-stage study was designed in which community-based individuals were first screened using the Community Screening Interview for Dementia. The second stage was a full clinical assessment, which included use of the Geriatric Depression Scale, of a smaller sub-sample of individuals selected on the basis of their performance in the screening interview. Prevalence of depression was estimated using sampling weights according to the sampling stratification scheme for clinical assessment.

Results: Some 2627 individuals were evaluated at the first stage in Indianapolis and 2806 in Ibadan. All were aged 69 years and over. Of these, 451 (17.2%) underwent clinical assessment in Indianapolis, while 605 (21.6%) were assessed in Ibadan. The prevalence estimates of both mild and severe depression were similar for the two sites (p = 0.1273 and p = 0.7093): 12.3% (mild depression) and 2.2% (severe depression) in Indianapolis and 19.8% and 1.6% respectively in Ibadan. Some differences were identified in association with demographic characteristics; for example, Ibadan men had a significantly higher prevalence of mild depression than Indianapolis men (p < 0.0001). Poor cognitive performance was associated with significantly higher rates of depression in Yoruba (p = 0.0039).

Conclusion: Prevalence of depression was similar for elderly African Americans and Yoruba despite considerable socioeconomic and cultural differences between these populations.

Visuoconstructional ability is an important domain for assessment in dementia. Use of graphomotor measures dominate this area; however, participants with low education produce results that cannot be easily interpreted. Our objective was to develop and validate a nongraphomotor assessment of visuoconstructional ability for use in dementia evaluations in persons with low or no education. In a longitudinal, population-based study of dementia among Yoruba residents of Ibadan, Nigeria aged 65 years and older, participants underwent clinical assessment with a battery of cognitive tests and consensus diagnosis. Performance on two visuoconstructional tests, Constructional Praxis and Stick Design, were compared. Gender, age, and education affected performance on both tests. The Stick Design test was more acceptable than Constructional Praxis as measured by the number of participants with total test failure (3.9% vs. 15.1%). The Stick Design test was significantly more sensitive to cognitive impairment and dementia than the Constructional Praxis test. We conclude that Stick Design is a reasonable test of visuoconstructional ability in older cohorts with very limited educational exposure and literacy. (JINS, 2005, 11, 598–605.)

Previous research has demonstrated dissociations between categorization and recognition performance in amnesic patients, supporting the idea that separate memory systems govern these tasks. However, previous research has also demonstrated that these dissociations are predicted by a single-system model that allows for reasonable parameter differences across groups. Generally, previous studies have employed categorization tasks that are less demanding than the recognition tasks. In this study, we distinguish between single-system and multiple-system accounts by testing memory-impaired individuals in a more demanding categorization task. These patients, just like previous amnesic participants, show a dissociation between categorization and recognition when tested in previously employed paradigms. However, they display a categorization deficit when tested in the more challenging categorization task. The results are interpreted as support for a single-system framework in which categorization and recognition depend on one representational system. (JINS, 2003, 9, 394–406.)

The CERAD Neuropsychological Battery, includes 7 measures: Verbal Fluency; Modified Boston Naming; Mini-Mental State; Word List Learning, Recall and Recognition; Constructional Praxis. It was originally developed to evaluate patients with a clinical diagnosis of Alzheimer's disease, but is increasingly used in epidemiological studies of the incidence and prevalence of dementia in the elderly. The current study reports norms for African American and White representative community residents 71 years of age and older in North Carolina, and compares performance with that of African Americans in Indianapolis and with Whites in the Monongahela Valley, Pennsylvania. For all 3 studies, increased education and younger age was related to better performance on each of the 7 measures. Sex differences, when present, tended to favor women. Although on average African Americans performed more poorly than Whites, with demographic characteristics controlled, no significant racial differences were found in the North Carolina sample. Both African American and White participants in North Carolina performed more poorly than their racial counterparts in the other 2 studies, possibly because of selection-induced differences in health and educational status. Nevertheless, the use of an identical evaluation battery, such as the CERAD neuropsychologic instrument, facilitates comparisons not otherwise possible, and should be encouraged. (JINS, 2001, 7, 502–509.)

Information on the clinical utility of neuropsychological tests in non-North-American samples is limited. We examined the diagnostic efficacy of the Consortium to Establish a Registry for Alzheimer's Disease (CERAD) neuropsychological battery in Jamaican men and women age 65 and older. A total of 72 elders were diagnosed as normal and 12 were demented based on history, physical, and neurological examination. Independent of this medical examination, participants were tested with the CERAD battery. Normal controls scored significantly better than dementia patients on all tests in the CERAD battery. A discriminant function found that a combination of Word List Learning Sum Recall and Boston Naming Test correctly classified a total of 81% of the cases (83% of the dements and 81% of the normal controls). This study is the first to demonstrate the clinical utility of the CERAD neuropsychological battery in the differential diagnosis of memory disorders of the aged in a non-North-American sample. (JINS, 1999, 5, 255–259.)

Three patients with Gerstmann-Sträussler-Scheinker disease (GSS) caused by a serine-for-phenylalanine substitution at codon 198 of the prion protein gene (PRNP) were compared to 9 age- and education-matched non-mutation-carriers from the same large Indiana kindred (GSS–IK) on a comprehensive neuropsychological test battery. Clinically significant impairments in intelligence, secondary memory, attention and cognitive processing speed, executive ability, and manual motor skills were noted in 2 patients. The wide range and the severity of the cognitive deficits indicated generalized cerebral dysfunction consistent with global dementia. One patient, symptomatic for less than 1 year, had more selective deficits involving memory, motor skills, and verbal fluency, suggesting early subcortical involvement. (JINS, 1997, 3, 169–178.)