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Digital voice recordings can offer affordable, accessible ways to evaluate behavior and function. We assessed how combining different low-level voice descriptors can evaluate cognitive status. Using voice recordings from neuropsychological exams at the Framingham Heart Study, we developed a machine learning framework fusing spectral, prosodic, and sound quality measures early in the training cycle. The model's area under the receiver operating characteristic curve was 0.832 (±0.034) in differentiating persons with dementia from those who had normal cognition. This offers a data-driven framework for analyzing minimally processed voice recordings for cognitive assessment, highlighting the value of digital technologies in disease detection and intervention. [ABSTRACT FROM AUTHOR]

Background: Identification of reliable, affordable, and easy-to-use strategies for detection of dementia is sorely needed. Digital technologies, such as individual voice recordings, offer an attractive modality to assess cognition but methods that could automatically analyze such data are not readily available. Methods and findings: We used 1264 voice recordings of neuropsychological examinations administered to participants from the Framingham Heart Study (FHS), a community-based longitudinal observational study. The recordings were 73 min in duration, on average, and contained at least two speakers (participant and examiner). Of the total voice recordings, 483 were of participants with normal cognition (NC), 451 recordings were of participants with mild cognitive impairment (MCI), and 330 were of participants with dementia (DE). We developed two deep learning models (a two-level long short-term memory (LSTM) network and a convolutional neural network (CNN)), which used the audio recordings to classify if the recording included a participant with only NC or only DE and to differentiate between recordings corresponding to those that had DE from those who did not have DE (i.e., NDE (NC+MCI)). Based on 5-fold cross-validation, the LSTM model achieved a mean (±std) area under the receiver operating characteristic curve (AUC) of 0.740 ± 0.017, mean balanced accuracy of 0.647 ± 0.027, and mean weighted F1 score of 0.596 ± 0.047 in classifying cases with DE from those with NC. The CNN model achieved a mean AUC of 0.805 ± 0.027, mean balanced accuracy of 0.743 ± 0.015, and mean weighted F1 score of 0.742 ± 0.033 in classifying cases with DE from those with NC. For the task related to the classification of participants with DE from NDE, the LSTM model achieved a mean AUC of 0.734 ± 0.014, mean balanced accuracy of 0.675 ± 0.013, and mean weighted F1 score of 0.671 ± 0.015. The CNN model achieved a mean AUC of 0.746 ± 0.021, mean balanced accuracy of 0.652 ± 0.020, and mean weighted F1 score of 0.635 ± 0.031 in classifying cases with DE from those who were NDE. Conclusion: This proof-of-concept study demonstrates that automated deep learning-driven processing of audio recordings of neuropsychological testing performed on individuals recruited within a community cohort setting can facilitate dementia screening. [ABSTRACT FROM AUTHOR]

Background: Early prediction of dementia risk is crucial for effective interventions. Given the known etiologic heterogeneity, machine learning methods leveraging multimodal data, such as clinical manifestations, neuroimaging biomarkers, and well-documented risk factors, could predict dementia more accurately than single modal data. Objective: This study aims to develop machine learning models that capitalize on neuropsychological (NP) tests, magnetic resonance imaging (MRI) measures, and clinical risk factors for 10-year dementia prediction. Methods: This study included participants from the Framingham Heart Study, and various data modalities such as NP tests, MRI measures, and demographic variables were collected. CatBoost was used with Optuna hyperparameter optimization to create prediction models for 10-year dementia risk using different combinations of data modalities. The contribution of each modality and feature for the prediction task was also quantified using Shapley values. Results: This study included 1,031 participants with normal cognitive status at baseline (age 75±5 years, 55.3% women), of whom 205 were diagnosed with dementia during the 10-year follow-up. The model built on three modalities demonstrated the best dementia prediction performance (AUC 0.90±0.01) compared to single modality models (AUC range: 0.82–0.84). MRI measures contributed most to dementia prediction (mean absolute Shapley value: 3.19), suggesting the necessity of multimodal inputs. Conclusion: This study shows that a multimodal machine learning framework had a superior performance for 10-year dementia risk prediction. The model can be used to increase vigilance for cognitive deterioration and select high-risk individuals for early intervention and risk management. [ABSTRACT FROM AUTHOR]

Background: Widespread dementia detection could increase clinical trial candidates and enable appropriate interventions. Since the Clock Drawing Test (CDT) can be potentially used for diagnosing dementia-related disorders, it can be leveraged to develop a computer-aided screening tool.Objective: To evaluate if a machine learning model that uses images from the CDT can predict mild cognitive impairment or dementia.Methods: Images of an analog clock drawn by 3,263 cognitively intact and 160 impaired subjects were collected during in-person dementia evaluations by the Framingham Heart Study. We processed the CDT images, participant's age, and education level using a deep learning algorithm to predict dementia status.Results: When only the CDT images were used, the deep learning model predicted dementia status with an area under the receiver operating characteristic curve (AUC) of 81.3% ± 4.3%. A composite logistic regression model using age, level of education, and the predictions from the CDT-only model, yielded an average AUC and average F1 score of 91.9% ±1.1% and 94.6% ±0.4%, respectively.Conclusion: Our modeling framework establishes a proof-of-principle that deep learning can be applied on images derived from the CDT to predict dementia status. When fully validated, this approach can offer a cost-effective and easily deployable mechanism for detecting cognitive impairment. [ABSTRACT FROM AUTHOR]

Alzheimer's disease is the primary cause of dementia worldwide, with an increasing morbidity burden that may outstrip diagnosis and management capacity as the population ages. Current methods integrate patient history, neuropsychological testing and MRI to identify likely cases, yet effective practices remain variably applied and lacking in sensitivity and specificity. Here we report an interpretable deep learning strategy that delineates unique Alzheimer's disease signatures from multimodal inputs of MRI, age, gender, and Mini-Mental State Examination score. Our framework linked a fully convolutional network, which constructs high resolution maps of disease probability from local brain structure to a multilayer perceptron and generates precise, intuitive visualization of individual Alzheimer's disease risk en route to accurate diagnosis. The model was trained using clinically diagnosed Alzheimer's disease and cognitively normal subjects from the Alzheimer's Disease Neuroimaging Initiative (ADNI) dataset (n = 417) and validated on three independent cohorts: the Australian Imaging, Biomarker and Lifestyle Flagship Study of Ageing (AIBL) (n = 382), the Framingham Heart Study (n = 102), and the National Alzheimer's Coordinating Center (NACC) (n = 582). Performance of the model that used the multimodal inputs was consistent across datasets, with mean area under curve values of 0.996, 0.974, 0.876 and 0.954 for the ADNI study, AIBL, Framingham Heart Study and NACC datasets, respectively. Moreover, our approach exceeded the diagnostic performance of a multi-institutional team of practicing neurologists (n = 11), and high-risk cerebral regions predicted by the model closely tracked post-mortem histopathological findings. This framework provides a clinically adaptable strategy for using routinely available imaging techniques such as MRI to generate nuanced neuroimaging signatures for Alzheimer's disease diagnosis, as well as a generalizable approach for linking deep learning to pathophysiological processes in human disease. [ABSTRACT FROM AUTHOR]