Cancer-related cognitive impairment and associated factors in a sample of older male oral-digestive cancer survivors.

OBJECTIVE: This study examines the demographic and clinical variables associated with cancer-related cognitive impairment (CRCI) in a sample of older, male, oral-digestive cancer survivors at VA Medical Centers in Boston and Houston. METHODS: A two-time point, longitudinal design was used, with cognitive assessment conducted at 6 and 18 months post-diagnosis. Using ANCOVA, the cognitive functioning of 88 older adults with head and neck, esophageal, gastric, or colorectal cancers was compared with that of 88 healthy controls. Paired t-tests examined cognitive change over time in the cancer group. Hierarchical linear regression examined variables potentially associated with cognitive impairment at 18 months. RESULTS: Forty-eight percent of cancer patients exhibited cognitive impairment 6 months post-cancer diagnosis, and 40% at 18 months. Cancer survivors were impaired relative to controls on measures of sustained attention, memory, and verbal fluency at 18 months, controlling for age. Older age, low hemoglobin, and cancer-related PTSD were associated with worse cognition at 18 months. CONCLUSIONS: CRCI is more frequent in older adults than reported in studies of younger adults and may be more frequent in men. Potential areas of intervention for CRCI include psychotherapy for cancer-related PTSD, treatment of anemia, and awareness of particularly vulnerable cognitive domains such as sustained attention, memory, and verbal fluency.

Validation of the German Montreal-Cognitive-Assessment-H for hearing-impaired.

Background: Hearing loss and dementia are highly prevalent in older age and often co-occur. Most neurocognitive screening tests are auditory-based, and performance can be affected by hearing loss. To address the need for a cognitive screening test suitable for people with hearing loss, a visual version of the Montreal-Cognitive-Assessment was developed and recently validated in English (MoCA-H), with good sensitivity and specificity for identifying cases of dementia. As the MoCA is known to perform differently across languages, revalidation of the German MoCA-H was necessary. The aim of the present study was to assess the diagnostic accuracy of the German MoCA-H among those with normal cognition, mild cognitive impairment (MCI) and dementia and to determine an appropriate performance cut- off. Materials and methods: A total of 346 participants aged 60-97 years (M = 77.18, SD = 9.56) were included; 160 were cognitively healthy, 79 with MCI and 107 were living with dementia based on the GPCOG and a detailed medical questionnaire as well as a comprehensive examination by a neurologist in case of cognitive impairment. Performance cut-offs for normal cognition, MCI and dementia were estimated for the MoCA-H score and z-scores using the English MoCA-H cut-off, the balanced cut-off and the Youden's Index. Results: A mean score of 25.49 (SD = 3.01) points in the German MoCA-H was achieved in cognitively healthy participants, 20.08 (SD = 2.29) in the MCI and 15.80 (SD = 3.85) in the dementia group. The optimum cut-off for the detection of dementia was ≤21 points with a sensitivity of 96.3% and a specificity of 90%. In the MCI group, a cut-off range between 22 and 24 points is proposed to increase diagnostic accuracy to a sensitivity and specificity of 97.5 and 90%, respectively. Conclusion: The German MoCA-H seems to be a sensitive screening test for MCI and dementia and should replace commonly used auditory-based cognitive screening tests in older adults. The choice of a cut-off range might help to better reflect the difficulty in clinical reality in detecting MCI. However, screening test batteries cannot replace a comprehensive cognitive evaluation.

Alternate-form reliability of the Montreal cognitive assessment screening test in a clinical setting.

AIMS: The Montreal Cognitive Assessment (MoCA) has gained recognition for its validity in detecting cognitive impairment in several clinical populations. For serial assessments, alternate forms are needed to overcome possible practice effects. Our objective was to investigate the reliability of two German MoCA alternate forms for longitudinal assessment applications. METHODS: The original and one of two alternate forms of the MoCA were administered within a 60-min interval of a clinical interview in a counterbalanced order to 100 healthy elderly controls, 30 patients with mild cognitive impairment (MCI) and 30 patients with Alzheimer's disease (AD). The diagnosis of the majority of patients was supported by in vivo AD pathology biomarkers. RESULTS: There was a strong correlation between the alternate forms and the original MoCA in all groups, but particularly in the clinical samples. Total mean scores did not differ significantly between the MoCA versions, even taking into account the presentation order. As in previous studies, age and education influenced performance in the MoCA. The same pattern of group differences (controls > MCI > AD) was observed for each of the versions. CONCLUSION: All three forms can be reliably and interchangeably used in serial cognitive assessment, confirming the MoCA's applicability in research and clinical longitudinal approaches.

Evaluation of the non-auditory neurocognitive test MoCA-HI for hearing-impaired.

Background: Since hearing loss and cognitive decline often co-occur among older adults, a cognitive screening test suitable for hearing-impaired people is of high clinical relevance. We report the first evaluation of a German language version of the Montreal Cognitive Assessment-Hearing Impaired version (MoCA-HI). Objective: The aim of the present study was to compare cognitively healthy participants with and without hearing loss, to examine the impact of age, sex, educational level and degree of hearing impairment on the German MoCA-HI performance, and to develop normative data. Material and methods: The German MoCA-HI was tested in 94 participants with normal or mild hearing impairment (group 1: 4PTA ≤ 40 dB on the better hearing ear) and 81 participants with moderate to profound hearing loss (group 2: 4PTA > 40 dB on the better hearing ear). Additionally, all participants performed the standard MoCA (version 8.2). Results: No significant group difference between group 1 and 2 was found in the MoCA-HI total score (p = 0.05). In contrast, group 1 performed significantly better than group 2 on the standard MoCA (p < 0.001). There was no difference between the MoCA and the MoCA-HI performance in group 1 (p = 0.12), whereas individuals of group 2 performed significantly better on the MoCA-HI than on the standard MoCA (p < 0.001). Test-retest reliability of the MoCA-HI was high (p < 0.001). Higher age (p < 0.001), male sex (p = 0.009) and lower education (p < 0.001) were associated with a lower overall MoCA-HI score. Based on the demographic data normative data were developed by a regression-based approach. Conclusion: The MoCA-HI is a cognitive screening test which is suitable for people with hearing impairment.

Vascular retinal biomarkers improves the detection of the likely cerebral amyloid status from hyperspectral retinal images.

INTRODUCTION: This study investigates the relationship between retinal image features and ß-amyloid (Aß) burden in the brain with the aim of developing a noninvasive method to predict the deposition of Aß in the brain of patients with Alzheimer's disease. METHODS: Retinal images from 20 cognitively impaired and 26 cognitively unimpaired cases were acquired (3 images per subject) using a hyperspectral retinal camera. The cerebral amyloid status was determined from binary reads by a panel of 3 expert raters on 18F-florbetaben positron-emission tomography (PET) studies. Image features from the hyperspectral retinal images were calculated, including vessels tortuosity and diameter and spatial-spectral texture measures in different retinal anatomical regions. RESULTS: Retinal venules of amyloid-positive subjects (Aß+) showed a higher mean tortuosity compared with the amyloid-negative (Aß-) subjects. Arteriolar diameter of Aß+ subjects was found to be higher than the Aß- subjects in a zone adjacent to the optical nerve head. Furthermore, a significant difference between texture measures built over retinal arterioles and their adjacent regions were observed in Aß+ subjects when compared with the Aß-. A classifier was trained to automatically discriminate subjects combining the extracted features. The classifier could discern Aß+ subjects from Aß- subjects with an accuracy of 85%. DISCUSSION: Significant differences in texture measures were observed in the spectral range 450 to 550 nm which is known as the spectral region known to be affected by scattering from amyloid aggregates in the retina. This study suggests that the inclusion of metrics related to the retinal vasculature and tissue-related textures extracted from vessels and surrounding regions could improve the discrimination performance of the cerebral amyloid status.

Non-invasive in vivo hyperspectral imaging of the retina for potential biomarker use in Alzheimer's disease.

Studies of rodent models of Alzheimer's disease (AD) and of human tissues suggest that the retinal changes that occur in AD, including the accumulation of amyloid beta (Aß), may serve as surrogate markers of brain Aß levels. As Aß has a wavelength-dependent effect on light scatter, we investigate the potential for in vivo retinal hyperspectral imaging to serve as a biomarker of brain Aß. Significant differences in the retinal reflectance spectra are found between individuals with high Aß burden on brain PET imaging and mild cognitive impairment (n = 15), and age-matched PET-negative controls (n = 20). Retinal imaging scores are correlated with brain Aß loads. The findings are validated in an independent cohort, using a second hyperspectral camera. A similar spectral difference is found between control and 5xFAD transgenic mice that accumulate Aß in the brain and retina. These findings indicate that retinal hyperspectral imaging may predict brain Aß load.

Validation of the Chinese Version of Montreal Cognitive Assessment Basic for Screening Mild Cognitive Impairment.

OBJECTIVES: To evaluate the effectiveness of the Chinese version of the Montreal Cognitive Assessment Basic (MoCA-BC) as a screening tool for detecting mild cognitive impairment (MCI) in Chinese elderly adults. DESIGN: Cross-sectional. SETTING: Huashan Hospital, Shanghai, China. PARTICIPANTS: Individuals with MCI (n = 264) and mild Alzheimer's disease (AD) (n = 160) were recruited from the Memory Clinic, Huashan Hospital; cognitively normal controls were recruited from Jinshan Community, Shanghai, China (n = 280). MEASUREMENTS: MoCA-BC scores. RESULTS: The MoCA-BC had good criterion-related validity (Pearson correlation coefficient MoCA-BC vs MMSE = 0.787) and reliable internal consistency (Cronbach alpha = 0.807). The optimal cutoff scores for MCI screening were 19 for individuals with no more than 6 years of education, 22 for individuals with 7 to 12 years of education, and 24 for individuals with more than 12 years of education. The MoCA-BC was superior to the MMSE for detecting MCI, with optimal sensitivity and specificity across all education groups using the above cutoff scores. CONCLUSION: The MoCA-BC is a reliable cognitive screening test across all education levels in Chinese elderly adults, with high acceptance and good reliability.

The Montreal Cognitive Assessment, MoCA: a brief screening tool for mild cognitive impairment.

OBJECTIVES: To develop a 10-minute cognitive screening tool (Montreal Cognitive Assessment, MoCA) to assist first-line physicians in detection of mild cognitive impairment (MCI), a clinical state that often progresses to dementia. DESIGN: Validation study. SETTING: A community clinic and an academic center. PARTICIPANTS: Ninety-four patients meeting MCI clinical criteria supported by psychometric measures, 93 patients with mild Alzheimer's disease (AD) (Mini-Mental State Examination (MMSE) score > or =17), and 90 healthy elderly controls (NC). MEASUREMENTS: The MoCA and MMSE were administered to all participants, and sensitivity and specificity of both measures were assessed for detection of MCI and mild AD. RESULTS: Using a cutoff score 26, the MMSE had a sensitivity of 18% to detect MCI, whereas the MoCA detected 90% of MCI subjects. In the mild AD group, the MMSE had a sensitivity of 78%, whereas the MoCA detected 100%. Specificity was excellent for both MMSE and MoCA (100% and 87%, respectively). CONCLUSION: MCI as an entity is evolving and somewhat controversial. The MoCA is a brief cognitive screening tool with high sensitivity and specificity for detecting MCI as currently conceptualized in patients performing in the normal range on the MMSE.

The Montreal Cognitive Assessment-Basic: A Screening Tool for Mild Cognitive Impairment in Illiterate and Low-Educated Elderly Adults.

OBJECTIVES: To assess the validity of a newly developed cognitive screening tool, the Montreal Cognitive Assessment-Basic (MoCA-B), in screening for mild cognitive impairment (MCI) in elderly adults with low education and varying literacy. DESIGN: Cross-sectional. SETTING: Community hospital in Bangkok, Thailand. PARTICIPANTS: Cognitively normal controls (n = 43) and individuals with MCI according to the National Institute on Aging-Alzheimer's Association work group criteria (n = 42) aged 55 to 80 with less than 5 years of education. MEASUREMENTS: MoCA-B scores. RESULTS: Mean MoCA-B scores were 26.3 ± 1.6 for illiterate controls and 21.3 ± 3.8 for illiterate participants with MCI (P < .001) and 26.6 ± 2.0 for literate controls and 23.0 ± 2.1 for literate participants with MCI (P < .001). MoCA-B scores did not differ significantly according to literacy, and multiple regression suggested no association with age or education. The optimal cutoff score of 24 out of 25 yielded 81% sensitivity and 86% specificity for MCI (area under the receiver operating characteristic curve = 0.90, P < .001). Test-retest reliability was 0.91 (P < .001), and internal consistency was 0.82. Administration time was 15 to 21 minutes. CONCLUSION: The MoCA-B appears to have excellent validity and addresses an unmet need by accurately screening for MCI in poorly educated older adults regardless of literacy.

Novel tau polymorphisms, tau haplotypes, and splicing in familial and sporadic frontotemporal dementia.

BACKGROUND: A subset of familial cases (FTDP-17) of frontotemporal dementia (FTD) are caused by mutations in the tau gene. The role of tau gene mutations and haplotypes in sporadic FTD and the functional consequences of tau polymorphisms are unknown. OBJECTIVES: To investigate (1) the frequency of known FTDP-17 mutations in familial and sporadic FTD and compare these results with previous studies; (2) whether the tau H1 haplotype is associated with FTD; and (3) the functional effect of intronic tau sequence variations. PATIENTS AND METHODS: Patients with familial and sporadic FTD were screened for mutations in the microtubule-binding region of tau. The frequencies of tau haplotypes and genotypes were compared between patients with FTD and control subjects. We analyzed the splicing effect of novel intronic polymorphisms associated with FTD. RESULTS: The P301L mutation was detected in 11% of familial FTD cases. The H1 haplotype was not overrepresented in patients with FTD, but the P301L mutation appeared on the background of the H2 tau haplotype. We identified 4 novel single nucleotide polymorphisms in intron 9 and a 9-base pair deletion in intron 4A. A C-to-T transition 177 base pairs upstream from exon 10 was significantly increased in patients with FTD compared with controls. Direct analysis of brain tissue from a patient with this variant showed an increase in exon 10-containing tau transcripts. CONCLUSIONS: Sequence variations in intronic or regulatory regions of tau may have previously unrecognized consequences leading to tau dysfunction and neurodegeneration.

Montreal Cognitive Assessment Memory Index Score (MoCA-MIS) as a predictor of conversion from mild cognitive impairment to Alzheimer's disease.

OBJECTIVES: To assess the usefulness of the Montreal Cognitive Assessment (MoCA) total score (MoCA-TS) and Memory Index Score (MoCA-MIS) in predicting conversion to Alzheimer's disease (AD) in individuals with mild cognitive impairment (MCI). DESIGN: Retrospective chart review. SETTING: Community-based memory clinic. PARTICIPANTS: Individuals meeting Petersen's MCI criteria (N = 165). MEASUREMENTS: Baseline MoCA scores at MCI diagnosis were collected from charts of eligible individuals with MCI, and MoCA-TS, MoCA-MIS, and a cognitive domain index score were calculated to assess their prognostic value in predicting conversion to AD. RESULTS: One hundred fourteen participants progressed to AD (MCI-AD), and 51 did not (nonconverters; MCI-NC); 90.5% of participants with MCI with a MoCA-TS less than 20/30 and a MoCA-MIS less than 7/15 at baseline converted to AD within the average follow-up period of 18 months, compared with 52.7% of participants with MCI above the cutoffs on both scores. Individuals with multiple-domain amnestic MCI had the highest AD conversion rates (73.9%). CONCLUSION: Identifying individuals with MCI at high risk of conversion to AD is important clinically and for selecting appropriate subjects for therapeutic trials. Individuals with MCI with a low MoCA-TS and a low newly devised memory index score (MoCA-MIS) are at greater risk of short-term conversion to AD.