Serum NfL and GFAP are associated with incident dementia and dementia mortality in older adults: The cardiovascular health study.

INTRODUCTION: Circulating neurofilament light chain (NfL) and glial fibrillary acidic protein (GFAP) have been independently associated with dementia risk. Their additive association, and their associations with dementia-specific mortality, have not been investigated. METHODS: We associated serum NfL, GFAP, total tau ,and ubiquitin carboxyl-terminal hydrolase-L1, measured in 1712 dementia-free adults, with 19-year incident dementia and dementia-specific mortality risk, and with 3-year cognitive decline. RESULTS: In adjusted models, being in the highest versus lowest tertile of NfL or GFAP associated with a hazard ratio (HR) of 1.49 (1.20-1.84) and 1.38 (1.15-1.66) for incident dementia, and 2.87 (1.79-4.61) and 2.76 (1.73-4.40) for dementia-specific mortality. Joint third versus first tertile exposure further increased risk; HR = 2.06 (1.60-2.67) and 9.22 (4.48-18.9). NfL was independently associated with accelerated cognitive decline. DISCUSSION: Circulating NfL and GFAP may, independently and jointly, provide useful clinical insight regarding dementia risk and prognosis.

Test-Retest Reliability and Minimal Detectable Change of Four Cognitive Tests in Community-Dwelling Older Adults.

BACKGROUND: Cognitive test-retest reliability measures can be used to evaluate meaningful changes in scores. OBJECTIVE: This analysis aimed to develop a comprehensive set of test-retest reliability values and minimal detectable change (MDC) values for a cognitive battery for community-dwelling older individuals in Australia and the U.S., for use in clinical practice. METHODS: Cognitive scores collected at baseline and year 1, in the ASPirin in Reducing Events in the Elderly clinical trial were used to calculate intraclass correlation coefficients (ICC) for four tests: Modified Mini-Mental State examination (3MS), Hopkins Verbal Learning Test-Revised (HVLT-R), single-letter Controlled Oral Word Association Test (COWAT-F), and Symbol Digit Modalities Test (SDMT). 16,956 participants aged 70 years and over (65 years and over for U.S. minorities) were included. ICCs were used to calculate MDC values for eight education and ethno-racial subgroups. RESULTS: All four cognitive tests had moderate (ICC > 0.5) to good (ICC > 0.7) test-retest reliability. ICCs ranged from 0.53 to 0.63 (3MS), 0.68 to 0.77 (SDMT), 0.56 to 0.64 (COWAT-F), 0.57 to 0.69 (HVLT-R total recall), and 0.57 to 0.70 (HVLT-R delayed recall) across the subgroups. MDC values ranged from 6.60 to 9.95 (3MS), 12.42 to 15.61 (SDMT), 6.34 to 8.34 (COWAT-F), 8.13 to 10.85 (HVLT-R total recall), and 4.00 to 5.62 (HVLT-R delayed recall). CONCLUSION: This large cohort of older individuals provides test-retest reliability and MDC values for four widely employed tests of cognitive function. These results can aid interpretation of cognitive scores and decline instead of relying on cross-sectional normative data alone.

Validation of the Cognitive Telephone Screening Instruments COGTEL and COGTEL+ in Identifying Clinically Diagnosed Neurocognitive Disorder Due to Alzheimer's Disease in a Naturalistic Clinical Setting.

BACKGROUND: Telephone-based neurocognitive instruments embody valuable tools in identifying cognitive impairment in research settings and lately also in clinical contexts due to the pandemic crisis. The accuracy of the Cognitive Telephone Screening Instrument (COGTEL) in detecting mild- (MiND) and major (MaND) neurocognitive disorder has not been studied yet. OBJECTIVE: Comparison of the utility of COGTEL and COGTEL+, which is enriched with orientation items, with the modified Mini-Mental State Examination (3MS) in detecting MiND and MaND due to Alzheimer's disease (AD) and assessment of the impact of COGTEL face-to-face-versus telephone administration on individual performance. METHODS: The study included 197 cognitively intact individuals (CI), being at least 45 years old, 95 and 65 patients with MiND and MaND due to AD, respectively. In 20 individuals COGTEL was administered both in face-to-face and telephone sessions. Statistical analyses included proportional odds logistic regression models, stratified repeated random subsampling used to recursive partitioning to training and validation set (70/30 ratio), and an appropriate F-test. RESULTS: All studied instruments were significant predictors of diagnostic outcome, but COGTEL+ and 3MS explained more variance relative to the original COGTEL. Except for the validation regression models including COGTEL in which the average misclassification error slightly exceeded 15%, in all other cases the average misclassification errors (%) were lower than 15%. COGTEL administration modality was not related to systematic over- or underestimation of performance on COGTEL. CONCLUSION: COGTEL+ is a valuable instrument in detecting MiND and MaND and can be administered in face-to-face or telephone sessions.

Lower Levels of Education Are Associated with Cognitive Impairment in the Old Order Amish.

BACKGROUND: Lower education has been reported to be associated with dementia. However, many studies have been done in settings where 12 years of formal education is the standard. Formal schooling in the Old Order Amish communities (OOA) ends at 8th grade which, along with their genetic homogeneity, makes it an interesting population to study the effect of education on cognitive impairment. OBJECTIVE: The objective of this study was to examine the association of education with cognitive function in individuals from the OOA. We hypothesized that small differences in educational attainment at lower levels of formal education were associated with risk for cognitive impairment. METHODS: Data of 2,426 individuals from the OOA aged 54-99 were analyzed. The Modified Mini-Mental State Examination (3MS-R) was used to classify participants as CI or normal. Individuals were classified into three education categories: <8, 8, and >8 years of education. To measure the association of education with cognitive status, a logistic regression model was performed adding age and sex as covariates. RESULTS: Our results showed that individuals who attained lowest levels of education (<8 and 8) had a higher probability of becoming cognitvely impaired compared with people attending >8 years (OR = 2.96 and 1.85). CONCLUSION: Even within a setting of low levels of formal education, small differences in educational attainment can still be associated with the risk of cognitive impairment. Given the homogeneity of the OOA, these results are less likely to be biased by differences in socioeconomic backgrounds.

Cognitive Impairment, P300, and Transforming Growth Factor ß1 in Different Forms of Dementia.

BACKGROUND: There are currently few biomarkers to assist in early diagnosis of dementias. OBJECTIVE: To distinguish between different dementias: Alzheimer's disease (AD), vascular dementia (VaD), and Parkinson's disease dementia (PDD) using simple neurophysiologic (P300) and laboratory markers (transforming growth factor ß1 "TGF-ß1"). METHODS: The study included 15 patients for each type of dementia and 25 age- and sex-matched control subjects. Dementia patients were diagnosed according to the Diagnostic and Statistical Manual of Mental Disorders 4th edition-revised (DSM-IV-R). Modified Mini-Mental State Examination (3MS), Memory Assessment Scale (MAS), P300, and TGF-ß1 were examined for each participant. RESULTS: There were no significant differences between groups as regard to age, sex, and education, social, and economic levels. Significant differences between groups were observed in registration and naming variables of the 3MS. Compared with the control group, P300 latency was prolonged in all groups, although to a greater extent in AD and PDD than in VaD. A serum level of TGF-ß1 was significantly elevated in all groups but was significantly higher in AD and VaD than in PDD. 3MS tended to correlate with P300 more than TGF-ß1, and to be stronger in AD than the other groups. CONCLUSION: Measurements of P300 latency and serum levels of TGF-ß1 can help distinguish AD, PDD, and VaD. P300 was more prolonged in AD and PDD than VaD whereas TGF-ß1 was significantly higher in AD and VaD than PDD. Thus P300 and TGF-ß1 may be useful biomarkers for detection and evaluation of the extent of cognitive dysfunction.

Adaptation of the Modified Mini-Mental State Examination (3MS) and Determination of Its Normative Values in Turkey.

BACKGROUND/AIMS: This study aimed to adapt the Modified Mini-Mental State Examination (3MS) and determine its normative values in Turkey. METHODS: After translation and cultural adaptation processes, a population-based study was conducted between February and June 2016 in Ankara with individuals over the age of 55 years. Subjects with a previous diagnosis of dementia along with neuropsychiatric disorders that might affect cognition were excluded. Data analyses were performed to assess the association of sociodemographic variables with 3MS scores. RESULTS: Two versions of the Turkish 3MS (for educated and minimally educated individuals) were developed. A total of 2,235 participants were included in the field study. After exclusion, the data on the final sample of 1,909 individuals were analyzed, where age, gender, and education accounted for variance in 3MS scores. Younger age and higher educational attainment were associated with better 3MS performance. CONCLUSIONS: A widely applicable dementia screening test was adapted to Turkish and its normative values were determined. The test will make it possible to evaluate the cognitive performance of both educated and minimally educated elderly individuals based on their age, gender, and educational level.

Analysis of Causative Factors and Effects to Cognitive Functions of Cerebral White Matter Changes

BACKGROUND: The aim of this study was to identify causative factors for cerebral white matter changes on MRI and relationship between cerebral white matter changes and cognitive function. METHODS: The patients who were admitted to the Department of Neurology ward or visited to outpatient clinic at the Chungnam National University Hospital from September 1999 to July 2000 were selected. All patients underwent brain MRI with 1.5 T for determination of degree and distribution of cerebral white matter changes. The patients were evaluated their cognitive function with the Mini Mental State Examination (MMSE) and the Modified Mini-Mental State Examination (3MS), which has more extensive and detailed tool for fluency and memory domains of cognition compared with the MMSE. Statistical analyses were performed to identify whether there was difference in causative factors and cognitive status between patients with white matter change and patients without white matter changes. RESULTS: White matter changes were significantly more common in patients with hypertension and women. On correlation analyses, hypertension and aging were significantly related with cerebral white matter changes. General cognitive status in patients with white matter changes were worse than those of patients without white matter changes and of control group. Frontal lobe functions like fluency, attention, and visuo-constructive function were especially affected by white matter changes on the 3MS. CONCLUSIONS: Hypertension, female sex and aging may contribute to the development of cerebral white matter changes. Cerebral white matter changes may be responsible for the general cognitive decline. (J Korean Neurol Assoc 19(5):471~477, 2001)