Alzheimer’s Disease and Parkinson Dementia Distinguished by Cognitive Marker

Abstract Background Temporary memory binding (TMB) has been shown to be specifically affected by Alzheimer’s disease (AD) when it is assessed via free recall and titrating the task demands to equate baseline performance across patients. Methods Patients with Parkinson’s disease (PD) were subdivided into patients with and without cognitive impairment and compared with AD and amnestic mild cognitive impairment (aMCI) patients on their performance on the TMB. Results The results show that only patients with AD dementia present with impaired TMB performance. Receiver operating characteristic curve analyses showed that TMB holds high sensitivity and specificity for aMCI and AD relative to PD groups and healthy controls. Conclusion The TMB is sensitive to the neurodegenerative mechanisms leading to AD dementia but not to those underpinning PD dementia. As such, TMB task can aid the differential diagnosis of these common forms of dementia.

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Easy Screening for Mild Alzheimer's Disease and Mild Cognitive Impairment from Elderly Speech

Current Alzheimer Research ◽

10.2174/1567205014666171120144343 ◽

2018 ◽

Vol 15 (2) ◽

pp. 104-110 ◽

Cited By ~ 3

Author(s):

Shohei Kato ◽

Akira Homma ◽

Takuto Sakuma

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Characteristic Curve ◽

Linear Regression Analysis ◽

Speech Sound ◽

The Elderly ◽

Speech Sounds ◽

Mel Frequency Cepstral Coefficients

Objective: This study presents a novel approach for early detection of cognitive impairment in the elderly. The approach incorporates the use of speech sound analysis, multivariate statistics, and data-mining techniques. We have developed a speech prosody-based cognitive impairment rating (SPCIR) that can distinguish between cognitively normal controls and elderly people with mild Alzheimer's disease (mAD) or mild cognitive impairment (MCI) using prosodic signals extracted from elderly speech while administering a questionnaire. Two hundred and seventy-three Japanese subjects (73 males and 200 females between the ages of 65 and 96) participated in this study. The authors collected speech sounds from segments of dialogue during a revised Hasegawa's dementia scale (HDS-R) examination and talking about topics related to hometown, childhood, and school. The segments correspond to speech sounds from answers to questions regarding birthdate (T1), the name of the subject's elementary school (T2), time orientation (Q2), and repetition of three-digit numbers backward (Q6). As many prosodic features as possible were extracted from each of the speech sounds, including fundamental frequency, formant, and intensity features and mel-frequency cepstral coefficients. They were refined using principal component analysis and/or feature selection. The authors calculated an SPCIR using multiple linear regression analysis. Conclusion: In addition, this study proposes a binary discrimination model of SPCIR using multivariate logistic regression and model selection with receiver operating characteristic curve analysis and reports on the sensitivity and specificity of SPCIR for diagnosis (control vs. MCI/mAD). The study also reports discriminative performances well, thereby suggesting that the proposed approach might be an effective tool for screening the elderly for mAD and MCI.

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Using Fractional Anisotropy Imaging to Detect Mild Cognitive Impairment and Alzheimer’s Disease among Mexican Americans and Non-Hispanic Whites: A HABLE Study

Dementia and Geriatric Cognitive Disorders ◽

10.1159/000518102 ◽

2021 ◽

pp. 1-8

Author(s):

James R. Hall ◽

Leigh A. Johnson ◽

Fan Zhang ◽

Melissa Petersen ◽

Arthur W. Toga ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Fractional Anisotropy ◽

Mexican Americans ◽

Diffusion Tensor ◽

Characteristic Curve ◽

Aging Brain ◽

Community Based

Introduction: Alzheimer’s disease (AD) is the most frequently occurring neurodegenerative disease; however, little work has been conducted examining biomarkers of AD among Mexican Americans. Here, we examined diffusion tensor MRI marker profiles for detecting mild cognitive impairment (MCI) and dementia in a multi-ethnic cohort. Methods: 3T MRI measures of fractional anisotropy (FA) were examined among 1,636 participants of the ongoing community-based Health & Aging Brain among Latino Elders (HABLE) community-based study (Mexican American n = 851; non-Hispanic white n = 785). Results: The FA profile was highly accurate in detecting both MCI (area under the receiver operating characteristic curve [AUC] = 0.99) and dementia (AUC = 0.98). However, the FA profile varied significantly not only between diagnostic groups but also between Mexican Americans and non-Hispanic whites. Conclusion: Findings suggest that diffusion tensor imaging markers may have a role in the neurodiagnostic process for detecting MCI and dementia among diverse populations.

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Detection of gray matter microstructural changes in Alzheimer’s disease continuum using fiber orientation

10.21203/rs.3.rs-17303/v6 ◽

2020 ◽

Author(s):

Peter Lee ◽

Hang-Rai Kim ◽

Yong Jeong ◽

Alzheimer's Disease Neuroimaging Initiative

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Gray Matter ◽

Fiber Orientation ◽

Diffusion Tensor ◽

Mean Diffusivity ◽

High Sensitivity ◽

Normal Vector

Abstract Background This study aimed to investigate feasible gray matter microstructural biomarkers with high sensitivity for early Alzheimer’s disease (AD) detection. We propose a diffusion tensor imaging (DTI) measure, “radiality”, as an early AD biomarker. It is the dot product of the normal vector of the cortical surface and primary diffusion direction, which reflects the fiber orientation within the cortical column. Methods We analyzed neuroimages from the Alzheimer’s Disease Neuroimaging Initiative (ADNI) database, including images from 78 cognitively normal (CN), 50 early mild cognitive impairment (EMCI), 34 late mild cognitive impairment (LMCI), and 39 AD patients. We then evaluated the cortical thickness (CTh), mean diffusivity (MD), which are conventional AD magnetic resonance imaging (MRI) biomarkers, and the amount of accumulated amyloid and tau using positron emission tomography (PET). Radiality was projected on the gray matter surface to compare and validate the changes with different stages alongside other neuroimage biomarkers.Results The results revealed decreased radiality primarily in the entorhinal, insula, frontal, and temporal cortex with further progression of disease. In particular, radiality could delineate the difference between the CN and EMCI groups, while the other biomarkers could not. We examined the relationship between radiality and other biomarkers to validate its pathological evidence in AD. Overall, radiality showed a high association with conventional biomarkers. Additional ROI analysis revealed the dynamics of AD-related changes as stages onward.Conclusion Radiality in cortical gray matter showed AD-specific changes and relevance with other conventional AD biomarkers with high sensitivity. Moreover, radiality could identify the group differences seen in EMCI, representative of changes in early AD, which supports its superiority in early diagnosis compared to that possible with conventional biomarkers. We provide evidence of structural changes with cognitive impairment and suggest radiality as a sensitive biomarker for identifying early AD.

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Visuospatial memory impairment as a potential neurocognitive marker to predict tau pathology in Alzheimer’s continuum

Alzheimer s Research & Therapy ◽

10.1186/s13195-021-00909-1 ◽

2021 ◽

Vol 13 (1) ◽

Author(s):

Eun Hyun Seo ◽

Ho Jae Lim ◽

Hyung-Jun Yoon ◽

Kyu Yeong Choi ◽

Jang Jae Lee ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Medial Temporal Lobe ◽

Memory Impairment ◽

Prediction Models ◽

Characteristic Curve ◽

Amyloid Β ◽

Tau Pathology ◽

Discrimination Ability

Abstract Background Given that tau accumulation, not amyloid-β (Aβ) burden, is more closely connected with cognitive impairment in Alzheimer’s disease (AD), a detailed understanding of the tau-related characteristics of cognitive function is critical in both clinical and research settings. We investigated the association between phosphorylated tau (p-Tau) level and cognitive impairment across the AD continuum and the mediating role of medial temporal lobe (MTL) atrophy. We also developed a prediction model for abnormal tau accumulation. Methods We included participants from the Gwangju Alzheimer’s Disease and Related Dementia Cohort in Korea, who completed cerebrospinal fluid analysis and clinical evaluation, and corresponded to one of three groups according to the biomarkers of A and T profiles based on the National Institute on Aging and Alzheimer’s Association research framework. Multiple linear and logistic regression analyses were performed to examine the association between p-Tau and cognition and to develop prediction models. Receiver operating characteristic curve analysis was performed to examine the discrimination ability of the models. Results Among 185 participants, 93 were classified as A-T-, 23 as A+T-, and 69 as A+T+. There was an association between decreased visuospatial delayed memory performance and p-Tau level (B = − 0.754, β = − 0.363, p < 0.001), independent of other relevant variables (e.g., Aβ). MTL neurodegeneration was found to mediate the association between the two. Prediction models with visuospatial delayed memory alone (area under the curve [AUC] = 0.872) and visuospatial delayed memory and entorhinal thickness (AUC = 0.921) for abnormal tau accumulation were suggested and they were validated in an independent sample (AUC = 0.879 and 0.891, respectively). Conclusion It is crucial to identify sensitive cognitive measures that capture subtle cognitive impairment associated with underlying pathological changes. Preliminary findings from the current study might suggest that abnormal tau accumulation underlies episodic memory impairment, particularly visuospatial modality, in the AD continuum. Suggested models are potentially useful in predicting tau pathology, and might be utilized practically in the field.

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Serum aberrant expression of miR-24-3p and its diagnostic value in Alzheimer’s disease

Biomarkers in Medicine ◽

10.2217/bmm-2021-0098 ◽

2021 ◽

Author(s):

Lina Liu ◽

Luran Liu ◽

Yunting Lu ◽

Tianyuan Zhang ◽

Wenting Zhao

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Receiver Operating Characteristic Curve ◽

Receiver Operating Characteristic ◽

Operating Characteristic ◽

Characteristic Curve ◽

Diagnostic Value ◽

Healthy Controls ◽

Operating Characteristic Curve ◽

Receiver Operating

Aim: This study aimed to evaluate the effect of miR-24-3p in Alzheimer’s disease (AD). Materials & methods: A total of 198 participants were recruited in this study, including 104 AD patients and 94 healthy controls. Expression of miR-24-3p was detected using quantitative real-time PCR. Receiver-operating characteristic curve was used to assess the diagnostic value of miR-24-3p. In vitro AD model was established to evaluate the effect of miR-24-3p. The downstream target was detected by luciferase reporter gene assay. Results: Expression of miR-24-3p showed 1.6-fold increase in AD group compared with healthy controls, and a negative correlation of miR-24-3p with mini-mental state examination score was obtained. Receiver-operating characteristic curve showed satisfactory diagnostic accuracy. Downregulation of miR-24-3p promoted cell proliferation and inhibited cell apoptosis. KLF8 is a target gene of miR-24-3p. Conclusion: MiR-24-3p has a certain value in the diagnosis of AD and may be a potential biomarker.

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Tactile Angle Discrimination Decreases due to Subjective Cognitive Decline in Alzheimer’s Disease

Current Alzheimer Research ◽

10.2174/1567205017666200309104033 ◽

2020 ◽

Vol 17 (2) ◽

pp. 168-176

Author(s):

Zhilin Zhang ◽

Guanqun Chen ◽

Jian Zhang ◽

Tianyi Yan ◽

Ritsu Go ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Decline ◽

Characteristic Curve ◽

Subjective Cognitive Decline ◽

Elderly Subjects ◽

Older Individuals ◽

Angle Discrimination

Background: Subjective Cognitive Decline (SCD) is the early preclinical stage of Alzheimer's Disease (AD). Previous study provided an invaluable contribution by showing that a tactile angle discrimination system can be used to distinguish between healthy older individuals and patients with mild cognitive impairment and AD. However, that study paid little attention to the relationship between tactile angle discrimination and SCD. Therefore, a means of differentiating Normal Controls (NCs), elderly subjects with SCD, patients with amnestic Mild Cognitive Impairment (aMCI), and AD is urgently needed. Methods: In the present study, we developed a novel tactile discrimination device that uses angle stimulation applied to the index finger pad to identify very small differences in angle discrimination between the NC (n = 30), SCD (n = 30), aMCI (n = 30), and AD (n = 30) groups. Using a three-alternative forced-choice and staircase method, we analyzed the average accuracy and threshold of angle discrimination. Results: We found that accuracy significantly decreased while thresholds of angle discrimination increased in the groups in the following order: NC, SCD, aMCI, and AD. The area under the receiver operating characteristic curve also indicated that the tactile angle discrimination threshold was better than Mini-Mental State Examination scores in distinguishing NC individuals and SCD patients. Conclusion: These findings emphasize the importance of tactile working memory dysfunction in explaining the cognitive decline in angle discrimination that occurs in SCD to AD patients and offer further insight into the very early detection of subjects with AD.

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Aggregation of Abnormal Memory Scores and Risk of Incident Alzheimer’s Disease Dementia: A Measure of Objective Memory Impairment in Amnestic Mild Cognitive Impairment

Journal of the International Neuropsychological Society ◽

10.1017/s135561772000079x ◽

2020 ◽

pp. 1-12

Author(s):

Nicholas I. Bradfield ◽

Kathryn A. Ellis ◽

Greg Savage ◽

Paul Maruff ◽

Samantha Burnham ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Sex Education ◽

Memory Impairment ◽

Characteristic Curve ◽

Imaging Biomarkers ◽

Subjective Memory ◽

Prognostic Stratification

Abstract Objectives: The criteria for objective memory impairment in mild cognitive impairment (MCI) are vaguely defined. Aggregating the number of abnormal memory scores (NAMS) is one way to operationalise memory impairment, which we hypothesised would predict progression to Alzheimer’s disease (AD) dementia. Methods: As part of the Australian Imaging, Biomarkers and Lifestyle Flagship Study of Ageing, 896 older adults who did not have dementia were administered a psychometric battery including three neuropsychological tests of memory, yielding 10 indices of memory. We calculated the number of memory scores corresponding to z ≤ −1.5 (i.e., NAMS) for each participant. Incident diagnosis of AD dementia was established by consensus of an expert panel after 3 years. Results: Of the 722 (80.6%) participants who were followed up, 54 (7.5%) developed AD dementia. There was a strong correlation between NAMS and probability of developing AD dementia (r = .91, p = .0003). Each abnormal memory score conferred an additional 9.8% risk of progressing to AD dementia. The area under the receiver operating characteristic curve for NAMS was 0.87 [95% confidence interval (CI) .81–.93, p < .01]. The odds ratio for NAMS was 1.67 (95% CI 1.40–2.01, p < .01) after correcting for age, sex, education, estimated intelligence quotient, subjective memory complaint, Mini-Mental State Exam (MMSE) score and apolipoprotein E ϵ4 status. Conclusions: Aggregation of abnormal memory scores may be a useful way of operationalising objective memory impairment, predicting incident AD dementia and providing prognostic stratification for individuals with MCI.

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False Memory and Alzheimer’s Disease Pathology in Patients with Amnestic Mild Cognitive Impairment: A Study with Amyloid PET

Dementia and Geriatric Cognitive Disorders Extra ◽

10.1159/000516230 ◽

2021 ◽

pp. 172-180

Author(s):

Eun-Ji Choi ◽

Bum Joon Kim ◽

Hyung-Ji Kim ◽

Miseon Kwon ◽

Noh Eul Han ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Logistic Regression ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

False Memory ◽

Visual Recognition ◽

Characteristic Curve ◽

Amnestic Mild Cognitive Impairment ◽

Amyloid Pet

Introduction: False memory, observed as intrusion errors or false positives (FPs), is prevalent in patients with Alzheimer’s disease, but has yet to be thoroughly investigated in patients with amnestic mild cognitive impairment (a-MCI) with Alzheimer’s disease pathology (ADP). We analyzed false versus veridical memory in individuals with a-MCI and measured the utility of false memory for ADP discrimination. Methods: Patients with a-MCI who received neuropsychological testing and amyloid PET were included. Patients were categorized into “with” and “without ADP” groups according to PET results. Memory tests assessed veridical and false memory, and the verity of patient responses was analyzed. A logistic regression model was used to evaluate false memory efficiency in discriminating ADP, and the sensitivity and specificity at the optimal level were estimated using the receiver-operating characteristic curve. Results: Thirty-seven ADP and 46 non-ADP patients were enrolled. The ADP group made more FPs in the recognition tests, and their response verity was significantly lower in every delayed memory test. No group difference, however, was observed in the veridical memory. The logistic regression analysis demonstrated that as the FPs increased, the risk of ADP increased 1.31 and 1.36 times in the verbal and visual recognition tests, respectively. The discriminatory accuracy of the FPs was estimated “low” to “moderate” in the visual and verbal recognition, respectively, with an optimal cutoff above 2.5. Conclusion: Increased false memory was the only feature to discriminate ADP from non-ADP in individuals with a-MCI. Further studies regarding false memory and its mechanism are warranted.

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Alzheimer's disease in the NAS–NRC Registry of ageing twin veterans, IV. Performance characteristics of a two-stage telephone screening procedure for Alzheimer's dementia

Psychological Medicine ◽

10.1017/s0033291700033183 ◽

1995 ◽

Vol 25 (6) ◽

pp. 1211-1219 ◽

Cited By ~ 85

Author(s):

Joseph J. Gallos ◽

John C. S. Breitner

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Operating Characteristic ◽

Cognitive Status ◽

Alzheimer’S Dementia ◽

Screening Procedure ◽

Two Stage ◽

Alzheimer's Dementia ◽

Telephone Screening

SynopsisIn the course of a large twin study of Alzheimer's disease we used a two-stage telephone screening procedure. The modified Telephone Interview for Cognitive Status (TICS-m) served as an initial screen for dementia in 12709 individuals. The telephone Dementia Questionnaire (DQ) was then asked of collateral informants for subjects with TICS-m scores below 28, as well as for samples of persons with higher TICS-m scores. Based upon DQ responses, individuals with cognitive impairment not attributable to focal causes underwent assessment for the clinical diagnosis of Alzheimer's disease (‘Alzheimer's dementia’), as did their twins. Well-defined Alzheimer's dementia was apparent in 39 subjects. Employing a cut-off of 27 or lower as indicative of cognitive impairment, the sensitivity of the TICS-m in the detection of Alzheimer's dementia was estimated at >99% and specificity at 86%. Inclusion of the DQ increased the specificity at the 27/28 cut-point to 99%. The TICS-m score was associated with an area under the receiver operating characteristic (ROC) curve of 0·88 (95% confidence interval 0·81 to 0·94). The maximum number of cases of Alzheimer's dementia remaining undetected in the sample was estimated to be 34.

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Association between handgrip strength and cognition in a Chinese population with Alzheimer’s disease and mild cognitive impairment

BMC Geriatrics ◽

10.1186/s12877-021-02383-8 ◽

2021 ◽

Vol 21 (1) ◽

Author(s):

Hang Su ◽

Xiaokang Sun ◽

Fang Li ◽

Qihao Guo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Cognitive Impairment ◽

Mild Cognitive Impairment ◽

Cognitive Function ◽

Early Recognition ◽

Handgrip Strength ◽

Characteristic Curve ◽

Cognitive Status ◽

Cutoff Points

Abstract Background This study aimed to explore the level and changes in handgrip strength among preclinical Alzheimer’s disease (AD) and AD patients and to evaluate the association between handgrip strength and cognitive function. Methods A total of 1431 participants from the memory clinic of Shanghai JiaoTong University Affiliated Sixth People’s Hospital and community were enrolled in the final analysis, including 596 AD, 288 mild cognitive impairment (MCI), and 547 normal individuals (NC). All participants received a comprehensive neuropsychological assessment. Mini-Mental State Examination (MMSE), Montreal Cognitive Assessment-Basic (MoCA-BC), and the Chinese version of Addenbrooke’s Cognitive Examination III (ACE-III-CV) were used as cognitive tests. The receiver operating characteristic curve (ROC) was plotted to assess the power of handgrip strength as a screening measure to discriminate AD and MCI. Results The results showed that handgrip strength in the MCI group was significantly lower than that of NC group, and the AD group had a further decline (both P < 0.01). Multivariate logistic regression was performed with the handgrip strength quartiles, and the results showed that the ORs of AD for increasing levels of handgrip strength were 1.00, 0.58 (0.46–0.78), 0.51 (0.36–0.73), and 0.50 (0.35–0.68), showing a decreasing trend (Pfor trend < 0.01). The ROC curve demonstrated that the handgrip strength cutoff points for the identification of AD were 16.8 and 20.7 kg among the female participants above and under 70 yrs and 24.4 and 33.3 kg for the male participants above and under 70 yrs, respectively. Similarly, for the identification of MCI, cutoff points were 17.5 and 21.9 kg for females above 70 yrs and under 70 yrs, and 25.8 and 36.2 kg for males above 70 yrs and under 70 yrs, respectively. Conclusions Our study provided the further knowledge on the relationship between noncognitive features and cognition in populations with differing cognitive status, revealed that the stronger handgrip strength was associated with better performances on cognitive function. It can be speculated that handgrip strength can help early recognition of Chinese AD patients.

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