Forecasting the Progression of Alzheimer's Disease Using Neural Networks and a Novel Pre-Processing Algorithm

Alzheimer's disease (AD) is the most common neurodegenerative disease in older people. Despite considerable efforts to find a cure for AD, there is a 99.6% failure rate of clinical trials for AD drugs, likely because AD patients cannot easily be identified at early stages. This project investigated machine learning approaches to predict the clinical state of patients in future years to benefit AD research. Clinical data from 1737 patients was obtained from the Alzheimer's Disease Neuroimaging Initiative (ADNI) database and was processed using the "All-Pairs" technique, a novel methodology created for this project involving the comparison of all possible pairs of temporal data points for each patient. This data was then used to train various machine learning models. Models were evaluated using 7-fold cross-validation on the training dataset and confirmed using data from a separate testing dataset (110 patients). A neural network model was effective (mAUC = 0.866) at predicting the progression of AD on a month-by-month basis, both in patients who were initially cognitively normal and in patients suffering from mild cognitive impairment. Such a model could be used to identify patients at early stages of AD and who are therefore good candidates for clinical trials for AD therapeutics.Comment: 10 pages; updated acknowledgement

Artificial intelligence approaches to predicting and detecting cognitive decline in older adults: A conceptual review.

Preserving cognition and mental capacity is critical to aging with autonomy. Early detection of pathological cognitive decline facilitates the greatest impact of restorative or preventative treatments. Artificial Intelligence (AI) in healthcare is the use of computational algorithms that mimic human cognitive functions to analyze complex medical data. AI technologies like machine learning (ML) support the integration of biological, psychological, and social factors when approaching diagnosis, prognosis, and treatment of disease. This paper serves to acquaint clinicians and other stakeholders with the use, benefits, and limitations of AI for predicting, diagnosing, and classifying mild and major neurocognitive impairments, by providing a conceptual overview of this topic with emphasis on the features explored and AI techniques employed. We present studies that fell into six categories of features used for these purposes: (1) sociodemographics; (2) clinical and psychometric assessments; (3) neuroimaging and neurophysiology; (4) electronic health records and claims; (5) novel assessments (e.g., sensors for digital data); and (6) genomics/other omics. For each category we provide examples of AI approaches, including supervised and unsupervised ML, deep learning, and natural language processing. AI technology, still nascent in healthcare, has great potential to transform the way we diagnose and treat patients with neurocognitive disorders

Recognition of Famous Names Predicts Cognitive Decline in Healthy Elders

Objective: The ability to recognize familiar people is impaired in both Mild Cognitive Impairment (MCI) and Alzheimer’s Dementia (AD). In addition, both groups often demonstrate a time-limited temporal gradient (TG) in which well known people from decades earlier are better recalled than those learned recently. In this study, we examined the TG in cognitively intact elders for remote famous names (1950–1965) compared to more recent famous names (1995–2005). We hypothesized that the TG pattern on a famous name recognition task (FNRT) would predict future cognitive decline, and also show a significant correlation with hippocampal volume. Method: Seventy-eight healthy elders (ages 65–90) with age-appropriate cognitive functioning at baseline were administered a FNRT. Follow-up testing 18 months later produced two groups: Declining (≥ 1 SD reduction on at least one of three measures) and Stable (\u3c 1 SD). Results: The Declining group (N = 27) recognized fewer recent famous names than the Stable group (N = 51), although recognition for remote names was comparable. Baseline MRI volumes for both the left and right hippocampi were significantly smaller in the Declining group than the Stable group. Smaller baseline hippocampal volume was also significantly correlated with poorer performance for recent, but not remote famous names. Logistic regression analyses indicated that baseline TG performance was a significant predictor of group status (Declining vs. Stable) independent of chronological age and APOE ε4 inheritance. Conclusions: The TG for famous name recognition may serve as an early preclinical cognitive marker of cognitive decline in healthy older individual

Development and Validation of eRADAR: A Tool Using EHR Data to Detect Unrecognized Dementia.

ObjectivesEarly recognition of dementia would allow patients and their families to receive care earlier in the disease process, potentially improving care management and patient outcomes, yet nearly half of patients with dementia are undiagnosed. Our aim was to develop and validate an electronic health record (EHR)-based tool to help detect patients with unrecognized dementia (EHR Risk of Alzheimer's and Dementia Assessment Rule [eRADAR]).DesignRetrospective cohort study.SettingKaiser Permanente Washington (KPWA), an integrated healthcare delivery system.ParticipantsA total of 16 665 visits among 4330 participants in the Adult Changes in Thought (ACT) study, who undergo a comprehensive process to detect and diagnose dementia every 2 years and have linked KPWA EHR data, divided into development (70%) and validation (30%) samples.MeasurementsEHR predictors included demographics, medical diagnoses, vital signs, healthcare utilization, and medications within the previous 2 years. Unrecognized dementia was defined as detection in ACT before documentation in the KPWA EHR (ie, lack of dementia or memory loss diagnosis codes or dementia medication fills).ResultsOverall, 1015 ACT visits resulted in a diagnosis of incident dementia, of which 498 (49%) were unrecognized in the KPWA EHR. The final 31-predictor model included markers of dementia-related symptoms (eg, psychosis diagnoses, antidepressant fills), healthcare utilization pattern (eg, emergency department visits), and dementia risk factors (eg, cerebrovascular disease, diabetes). Discrimination was good in the development (C statistic = .78; 95% confidence interval [CI] = .76-.81) and validation (C statistic = .81; 95% CI = .78-.84) samples, and calibration was good based on plots of predicted vs observed risk. If patients with scores in the top 5% were flagged for additional evaluation, we estimate that 1 in 6 would have dementia.ConclusionThe eRADAR tool uses existing EHR data to detect patients with good accuracy who may have unrecognized dementia. J Am Geriatr Soc 68:103-111, 2019