Validation of a web-based cognitive test for early detection of Alzheimer's disease.

Suitability of the Montreal Cognitive Assessment versus the Mini-Mental State Examination in Detecting Vascular Cognitive Impairment

The influences of demographics, culture, language, and environmental changes on Mini-Mental State Examination (MMSE) scores are considerable. Using a sample of 7452 healthy, community-dwelling elderly Koreans, aged 55 to 94 years, who participated in the four ongoing geriatric cohorts in Korea, we investigated demographic influences on MMSE scores and derived normative data for this population. Geropsychiatrists strictly excluded subjects with cognitive disorders according to the protocol of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-K) Clinical Assessment Battery (CERAD-K-C). Education (standardized β = 0.463), age (standardized β = -0.303), and gender (standardized β = -0.057) had significant effects on MMSE scores (p < 0.001). The score of MMSE increase 0.379 point per 1-year education, decrease 0.188 per 1-year older, and decrease 0.491 in women compared to men. Education explained 30.4% of the scores' total variance, which was much larger than the variances explained by age (8.4%) or gender (0.3%). Accordingly, we present normative data for the MMSE stratified by education (0, 1-3, 4-6, 7-9, 10-12, and ≥ 13 years), age (60-69, 70-79, and 80-89 years), and gender. We provide contemporary education-, age-, and gender-stratified norms for the MMSE, derived from a large, community-dwelling elderly Korean population sample, which could be useful in evaluating individual MMSE scores.

Background: The relationship between hypertension and cognitive impairment has been investigated in the literature; several clinical studies suggested a relationship between hypertension and retinopathy. Methods: We examined the relationship between the retinopathy status and cognitive functions by using the Mini-Mental State Examination (MMSE) among hypertensive subjects older than 40 years who were admitted to our Family Medicine, Internal Medicine and Ophthalmology clinics. The subjects were categorized into three groups: group 1 = control subjects (n = 39), group 2 = hypertensive patients without retinopathy (n = 32), and group 3 = hypertensive patients with retinopathy (n = 25). Results: The number of patients with total MMSE scores less than 24 was distributed as follows: group 1: 3 patients (7.7%), group 2: 4 patients (12.5%), and group 3: 14 patients (56%). Hypertension was found to be related with a significant decrease in total MMSE scores in comparison with group 1 subjects (p < 0.001). Furthermore, retinopathy significantly correlated with lower MMSE scores among hypertensive patients (p = 0.001). Compared with group 1, group 3 showed a significant decrease in orientation (p = 0.001), registration (p = 0.001), attention and calculation (p = 0.004), recall (p = 0.009), and total (p < 0.001) MMSE scores. We also found a significant decrease in recall (p = 0.032) and total (p = 0.034) scores in group 3 when compared with group 2. There was a significant decrease in registration (p = 0.002) and total (p = 0.029) MMSE scores in group 2 when compared with group 1. We also observed negative correlations between duration of the disease and orientation (R = –0.597, n = 32, p = 0.001), and between duration of the disease and total (R = –0.495, n = 32, p = 0.006) scores in group 2. Conclusions: Hypertension was found to be related with a decline in MMSE scores. This relation was even more significant in the group of hypertensive patients with retinopathy. Thus, we suggest that cognitive tests be routinely used in the follow-up of hypertensive patients.

Background/Aims: The diagnostic accuracy of the German version of the revised Addenbrooke’s Cognitive Examination (ACE-R) in identifying mild cognitive impairment (MCI), mild dementia in Alzheimer’s disease (AD) and mild dementia in frontotemporal lobar degeneration (FTLD) in comparison with the conventional Mini Mental State Examination (MMSE) was assessed. Methods: The study encompasses 76 cognitively healthy elderly individuals, 75 patients with MCI, 56 with AD and 22 with FTLD. ACE-R and MMSE were validated against an expert diagnosis based on a comprehensive diagnostic procedure. Statistical analysis was performed using the receiver operating characteristic method and regression analyses. Results: The optimal cut-off score for the ACE-R for detecting MCI, AD, and FTLD was 86/87, 82/83 and 83/84, respectively. ACE-R was superior to MMSE only in the detection of patients with FTLD [area under the curve (AUC): 0.97 vs. 0.92], whilst the accuracy of the two instruments did not differ in identifying MCI and AD. The ratio of the scores of the memory ACE-R subtest to verbal fluency subtest contributed significantly to the discrimination between AD and FTLD (optimal cut-off score: 2.30/2.31, AUC: 0.77), whereas the MMSE and ACE-R total scores did not. Conclusion: The German ACE-R is superior to the most commonly employed MMSE in detecting mild dementia in FTLD and in the differential diagnosis between AD and FTLD. Thus it might serve as a valuable instrument as part of a comprehensive diagnostic workup in specialist centres/clinics contributing to the diagnosis and differential diagnosis of the cause of dementia.

The increasing burden of Alzheimer's disease (AD) emphasizes the need for effective diagnostic and therapeutic strategies. Despite available treatments targeting amyloid beta (Aβ) plaques, disease-modifying therapies remain elusive. Early detection of mild cognitive impairment (MCI) patients at risk for AD conversion is crucial, especially with anti-Aβ therapy. While plasma biomarkers hold promise in differentiating AD from MCI, evidence on predicting cognitive decline is lacking. This study's objectives were to evaluate whether plasma protein biomarkers could predict both cognitive decline in non-demented individuals and the conversion to AD in patients with MCI. This study was conducted as part of the Korean Longitudinal Study on Cognitive Aging and Dementia (KLOSCAD), a prospective, community-based cohort. Participants were based on plasma biomarker availability and clinical diagnosis at baseline. The study included MCI (n = 50), MCI-to-AD (n = 21), and cognitively unimpaired (CU, n = 40) participants. Baseline plasma concentrations of six proteins-total tau (tTau), phosphorylated tau at residue 181 (pTau181), amyloid beta 42 (Aβ42), amyloid beta 40 (Aβ40), neurofilament light chain (NFL), and glial fibrillary acidic protein (GFAP)-along with three derivative ratios (pTau181/tTau, Aβ42/Aβ40, pTau181/Aβ42) were analyzed to predict cognitive decline over a six-year follow-up period. Baseline protein biomarkers were stratified into tertiles (low, intermediate, and high) and analyzed using a linear mixed model (LMM) to predict longitudinal cognitive changes. In addition, Kaplan-Meier analysis was performed to discern whether protein biomarkers could predict AD conversion in the MCI subgroup. This prospective cohort study revealed that plasma NFL may predict longitudinal declines in Mini-Mental State Examination (MMSE) scores. In participants categorized as amyloid positive, the NFL biomarker demonstrated predictive performance for both MMSE and total scores of the Korean version of the Consortium to Establish a Registry for Alzheimer's Disease Assessment Packet (CERAD-TS) longitudinally. Additionally, as a baseline predictor, GFAP exhibited a significant association with cross-sectional cognitive impairment in the CERAD-TS measure, particularly in amyloid positive participants. Kaplan-Meier curve analysis indicated predictive performance of NFL, GFAP, tTau, and Aβ42/Aβ40 on MCI-to-AD conversion. This study suggests that plasma GFAP in non-demented participants may reflect baseline cross-sectional CERAD-TS scores, a measure of global cognitive function. Conversely, plasma NFL may predict longitudinal decline in MMSE and CERAD-TS scores in participants categorized as amyloid positive. Kaplan-Meier curve analysis suggests that NFL, GFAP, tTau, and Aβ42/Aβ40 are potentially robust predictors of future AD conversion.

Impaired Awareness of Deficits and Neuropsychiatric Symptoms in Early Alzheimer's Disease: The Danish Alzheimer Intervention Study (DAISY)

Neuropsychiatric symptoms (NPS) are both common in mild cognitive impairment and Alzheimer disease (AD). Studies have shown that some NPS such as apathy and depression are a key indicator for progression to AD. We compared Neuropsychiatric Inventory (NPI) total score and NPI subdomain score between mild cognitive impairment-converters (MCI-C) and mild cognitive impairment-nonconverters (MCI-NC) longitudinally for 6 years using the Alzheimer's Disease Neuroimaging Initiative (ADNI) database. In addition to the NPI, Mini-Mental State Examination (MMSE) scores were also compared to find out if MMSE scores would differ between different NPI groups. Lastly, a linear regression model was done on MMSE and NPI total score to establish a relationship between MMSE and NPI total score. The results in this study showed that NPI total scores between MCI-C and MCI-NC differed significantly throughout 6 years. MCI-C subjects had a higher mean NPI total score and lower MMSE score compared with MCI-NC subjects. In addition, MMSE scores were significantly different between the 3 groups of NPI total score. Subjects who have a high NPI score have the lowest mean MMSE score, thus demonstrating that NPI scores do indeed affect MMSE scores. Further analyses using a regression model revealed that a unit change in NPI total score lead to 0.1 to 0.3 decrease in MMSE. On the basis of the findings, this study showed evidence that increase in NPS burden (reflected by increase in NPI) over time predicts conversion to AD, whereas stability of symptoms (reflected by stable NPI score) favors nonconversion. Further study should investigate the underlying mechanisms that drive both NPS burden and cognitive decline.

To assess the utility of the computerized cognitive function assessment tool, CogEvo, as a screening tool for mild cognitive impairment in primary care, we explored the relationship between CogEvo performance, age, and the severity of cognitive dysfunction evaluated by the Mini-Mental State Examination (MMSE). The observational cross-sectional study included 209 individuals' data (mean age 79.4 ± 8.9 years). We conducted a correlation analysis between CogEvo and MMSE scores, compared the performance among the 3 cognitive function groups (MMSE ≥ 28 group; MMSE24-27 group; MMSE ≤ 23 group) using the MMSE cut-off, and evaluated CogEvo's predictive accuracy for cognitive dysfunction through ROC analysis. Both total CogEvo and MMSE scores significantly decreased with age. A significant positive correlation was observed between total CogEvo and MMSE scores, but a ceiling effect was detected in MMSE performance. Significant differences were observed in the total CogEvo score, including orientation and spatial cognitive function scores, among the 3 groups. CogEvo showed no educational bias. ROC analyses indicated moderate discrimination between the MMSE ≥ 28 group and the MMSE24-27 and MMSE ≤ 23 groups. The computer-administered CogEvo has the advantage of not exhibiting ceiling effects or educational bias like the MMSE, and was found to be able to detect age-related cognitive decline and impairment.

The clinical diagnostic criteria for frontotemporal degeneration (FTD) include relative preservation of memory and visuospatial function, in contradistinction to characteristics of Alzheimer’s disease (AD). The Mini-Mental State Examination (MMSE) contains items to assess these areas of cognition. In a retrospective case-control study of participants at two institutionally-based AD centers, we determined whether total MMSE and MMSE subscores would reflect the disease progression projected by the clinical criteria of FTD vs. AD. Participants were 44 subjects with FTD (7 pathologically confirmed) and 45 with pathologically confirmed AD. Each subject had at least two MMSEs with minimum inter-test intervals of 9 months. We compared annualized rates of change for total MMSE scores and cognitive domain subscores over time and between groups by two independent samples t-tests and proportion tests. The total MMSE score (p = 0.03) and language subscore (p = 0.02) showed a greater rate of decline for the FTD group than the AD group, although the constructional praxis item declined less rapidly in the FTD group (p = 0.018). Changes in MMSE subscores paralleled the clinical diagnostic criteria for FTD. The more rapid progression on the language subscore was observed in both language and behavioral variants of FTD.

The Alzheimer's Disease Assessment Scale (ADAS) is designed for screening of cognitive and non-cognitive dysfunctions characteristic of persons with probable Alzheimer's disease (AD). The cognitive part of the scale (ADAS-Cog) is both convenient for screening of probable AD and as a measure of cognitive functioning during drug intervention. The aim of this study was to translate the ADAS-Cognitive sub-test (ADAS-Cog) into Icelandic and to study its application in an elderly Icelandic population. The Mini-Mental State Examination (MMSE) and the ADAS-Cog were administered to 20 AD patients and 20 controls. Each patient was also rated on the Global Deterioration Scale (GDS). The probable AD patients were divided into two groups based on their GDS: 3-4 and 5-6 points. The patients were also divided into two groups based on their MMSE score: very mild to mild (23-30 points) and mild to moderate (15-22 points). Furthermore, the subjects were divided into two age groups: 65-76 and 77-92 years. Results revealed a highly significant difference on MMSE (22.3 - 3.4; 26.8 - 1.6; P < 0.05) and ADAS-Cog (18.4 - 7.7; 7.3 - 3.5; P < 0.05) scores for patients and controls respectively. AD patients also performed significantly worse than the elderly control group on eight of the 11 sub-tests. Thus, the present findings are mainly in line with those of previous studies. The scale exceeds other screening tests such as the MMSE in that it addresses in more detail the symptoms of AD and is valuable for early detection of the illness and staging. ADAS-Cog plays an important role in the diagnostic makeup of AD along with other detailed investigations, such as neuropsychological assessment.

T1-Weighted Imaging-Based Hippocampal Radiomics in the Diagnosis of Alzheimer's Disease

Brain degeneration in patients with Alzheimer’s disease (AD) results from the accumulation of pathological amyloid-β (Aβ) plaques and tau protein tangles, leading to altered plasma levels of biomarkers. However, few studies have investigated the association between plasma biomarkers and cognitive impairment in patients with AD. In this cross-sectional study, we investigated correlations between mini-mental state examination (MMSE) scores and levels of plasma biomarkers in patients with amnestic mild cognitive impairment (aMCI) and AD. Thirteen individuals with normal cognition, 40 patients with aMCI, and 37 patients with AD were enrolled. Immunomagnetic reduction was used to assess the levels of plasma biomarkers, including amyloid Aβ1-40, Aβ1-42, total tau protein (t-Tau), and phosphorylated tau protein (threonine 181, p-Tau181). Our analysis revealed a significant negative correlation between MMSE and both measures of tau, and a trend toward negative correlation between MMSE and Aβ1-42. In a longitudinal study involving three patients with aMCI and two patients with AD, we observed strong negative correlations (r < −0.8) between changes in MMSE scores and plasma levels of t-Tau. Our results suggest that plasma levels of t-Tau and p-Tau181 can be used to assess the severity of cognitive impairment in patients with AD. Furthermore, the results of our preliminary longitudinal study suggest that levels of t-Tau can be used to monitor the progression of cognitive decline in patients with aMCI/AD.

This study was designed to evaluate the microstructural integrity of white matter (WM) in amnestic mild cognitive impairment (MCI) and Alzheimer's disease (AD) among Han Chinese elderly using diffusion tensor imaging (DTI) technique, and to investigate the relationship between WM abnormalities and cognitive dysfunction. Sixty-four subjects (23 mild probable AD, 20 amnestic MCI, and 21 age-matched normal controls) who did not have visible WM lesion burden were analyzed. Fractional anisotropy (FA) and mean diffusivity were measured in normal-appearing WM (NAWM) using DTI with 64 encoding directions. The results were correlated with the scores of Mini-Mental State Examination (MMSE) and Cognitive Ability Screening Instrument (CASI). Statistical analysis showed the FA value in parietal WM was significantly lower in MCI compared to NC (P<0.001), and further decreased in AD compared to MCI (P=0.005). The lower FA and elevated mean diffusivity values were found in temporal WM, frontal WM, parahippocampal and posterior cingulate fibers of AD group compared to MCI and NC (all P<0.01). Canonical correlation analysis showed that the parietal FA values measured from all subjects were significantly correlated with the scores of CASI and MMSE (P<0.01). The results indicated that DTI can detect microstructural WM abnormalities in AD and amnestic MCI, and the measures were correlated with cognitive performance. In MCI, the abnormality was found to be limited within the parietal WM; and in AD a more widespread alteration was found in other brain regions as well.

Dementia with Lewy bodies (DLB) is the second most common neurodegenerative dementia, but it is often underdiagnosed and mistaken for Alzheimer's disease (AD) with sometimes lethal consequences. Over 35 studies have established the differences between DLB and AD in neuropsychological tests, but none have provided easy interpretations of common tests suitable for the clinician. The aim of this study was to suggest practical interpretations of the Mini-Mental State Examination (MMSE), clock drawing, and cube-copying to identify DLB and differentiate it from AD. Thirty-three DLB patients were matched according to gender, MMSE, and age with 66 AD patients. The median MMSE score was 24. Easy interpretations of the tests, including the MMSE orientation subscore, were sought for. The identified criteria to separate DLB from AD were (1) the MMSE orientation score x 3 > or = the total MMSE score, (2) an impaired clock drawing, and (3) a non-3D cube-copying. If (1) was fulfilled, the sensitivity and specificity were 100 and 57% in patients with MMSE 21-27. If (1) and (2) were fulfilled in patients with MMSE 21-27, the sensitivity and specificity were 93 and 70%. If at least two of the three criteria were fulfilled, the sensitivity was 85%, and the specificity 75% regardless of MMSE score. If the orientation score x 3 > or = the total MMSE score together with an impaired clock drawing and possibly a non-3D cube-copying, the patient should be thoroughly investigated according to the DLB consensus criteria.

Convergence of Clinical Staff Ratings and Research Ratings to Assess Patients With Schizophrenia in Nursing Homes