Detecting early signs of Alzheimer’s disease and related dementia onset from the EHR

Abstract As dementia is widely under-detected, a predictive model using electronic health records (EHR) could provide a method for early screening to implement preventive strategies. There is limited research on using EHR to identify persons with Alzheimer’s disease (AD) and related dementias (RD). In a data-driven approach, we used all ICD-9 diagnosis and CPT procedure codes from statewide inpatient, ambulatory surgery, and Medicare records, in addition to age at baseline and gender, to detect AD/RD from the Cache County Study on Memory in Aging (1995–2009). After removing participants diagnosed with dementia at baseline (n=335), 3882 (82%) Cache County Study participants could be linked to inpatient, ambulatory surgery, and/or Medicare EHR records; 484 (12.5%) of these 3882 had incident all-cause dementia, with 308 (7.9%) having AD/AD comorbid with RD; and 176 (4.5%) having RD without AD. We removed participant’s ICD-9 codes occurring after first AD/RD diagnoses. EHR features (~2000) along with gold-standard diagnoses as class labels were then used to train and detect AD and/or RD using a Gradient Boosting Trees machine learning algorithm. Models evaluated with nested cross-validation yielded AUCs of 0.70 for all-cause dementia, 0.69 for AD/AD comorbid with RD, and 0.67 for RD without AD. Key factors detecting AD/RD included age at enrollment, cardiovascular, metabolic, and kidney disease, and sleep disturbances, with feature importance varying by record type and time frame prior to dementia onset. Our findings suggest that a patient’s health status up to 12 years prior may be useful in identifying individuals at-risk for dementia development.

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Faculty Opinions recommendation of Pharmacotherapies for sleep disturbances in Alzheimer's disease.

Faculty Opinions – Post-Publication Peer Review of the Biomedical Literature ◽

10.3410/f.725273976.793502229 ◽

2014 ◽

Author(s):

Anand Kumar

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sleep Disturbances

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Decoding the Inter-relationship between Sleep Disorders and Alzheimer’s disease Pathogenesis

CNS & Neurological Disorders - Drug Targets ◽

10.2174/1871527319666200903161249 ◽

2020 ◽

Vol 19 ◽

Author(s):

Zeba Mueed ◽

Pankaj Kumar Rai ◽

Mohammad A. Kamal ◽

Nitesh Kumar Poddar

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sleep Disorders ◽

Sleep Disturbances ◽

Mammalian Target Of Rapamycin ◽

Light Therapy ◽

Paired Helical Filaments ◽

Bidirectional Relationship ◽

Causative Agents

Alzheimer’s disease (AD), characterized by abnormally phosphorylated tau, paired helical filaments (PHFs), neurofibrillary tangles (NFTs), deregulated mammalian target of rapamycin (mTOR), Aβ deposits, is a multifactorial disease with sleep disorders being one of the causative agents. Therefore, we have reviewed the literature and have tried to decode the existence of positive feedback, reciprocal and a bidirectional relationship allying between sleep disturbances and AD. Much light has been thrown on the role of tau pathology and amyloid pathology in sleep pathology and its association with AD pathology. We have also discussed the role of melatonin in regulating sleep disorders and AD. The neuroprotective action of melatonin via inhibiting tau hyperphosphorylation and Aβ deposition has also been pondered upon. Moreover, astrocytes involvement in aggravating AD has also been highlighted in this review. Several therapeutic approaches aimed at improving both sleep disorders and AD have been duly discussed such as administration of antidepressants and antihistamines, immunotherapy, metal chelators, melatonin supplementation, light therapy and physical activity. Despite consistent efforts, the complete etiology concerning sleep disorder and AD is still unclear. Therefore, further research is needed to unravel the mechanism involved and also to develop strategies that may help in obstructing AD in its preclinical stage.

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Interactions between sleep disturbances and Alzheimer’s disease on brain function: a preliminary study combining the static and dynamic functional MRI

Scientific Reports ◽

10.1038/s41598-019-55452-9 ◽

2019 ◽

Vol 9 (1) ◽

Cited By ~ 2

Author(s):

Kaicheng Li ◽

Xiao Luo ◽

Qingze Zeng ◽

Yerfan Jiaerken ◽

Shuyue Wang ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Risk Factor ◽

Sleep Disturbance ◽

Brain Function ◽

Sleep Disturbances ◽

Brain Activity ◽

Vascular Risk Factor ◽

Underlying Mechanism ◽

Amyloid Pet

AbstractThough sleep disturbance constitutes the risk factor for Alzheimer’s disease (AD), the underlying mechanism is still unclear. This study aims to explore the interaction between sleep disturbances and AD on brain function. We included 192 normal controls, 111 mild cognitive impairment (MCI), and 30 AD patients, with either poor or normal sleep (PS, NS, respectively). To explore the strength and stability of brain activity, we used static amplitude of low-frequency fluctuation (sALFF) and dynamic ALFF (dALFF) variance. Further, we examined white matter hyperintensities (WMH) and amyloid PET deposition, representing the vascular risk factor and AD-related hallmark, respectively. We observed that sleep disturbance significantly interacted with disease severity, exposing distinct effects on sALFF and dALFF variance. Interestingly, PS groups showed the dALFF variance trajectory of initially increased, then decreased and finally increased along the AD spectrum, while showing the opposite trajectory of sALFF. Further correlation analysis showed that the WMH burden correlates with dALFF variance in PS groups. Conclusively, our study suggested that sleep disturbance interacts with AD severity, expressing as effects of compensatory in MCI and de-compensatory in AD, respectively. Further, vascular impairment might act as important pathogenesis underlying the interaction effect between sleep and AD.

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Lighting and Alzheimer’s disease and related dementias: Spotlight on sleep and depression

Lighting Research and Technology ◽

10.1177/14771535211005835 ◽

2021 ◽

Vol 53 (5) ◽

pp. 405-422

Author(s):

MG Figueiro ◽

HC Kales

Keyword(s):

Alzheimer’S Disease ◽

Older Adults ◽

Alzheimer's Disease ◽

Neurodegenerative Disease ◽

Sleep Disturbances ◽

Well Being ◽

Pharmacological Intervention ◽

Negative Effects ◽

Health And Well Being ◽

Positive Results

Alzheimer’s disease and related dementias is the collective term for a progressive neurodegenerative disease for which there is presently no cure. This paper focuses on two symptoms of the disease, sleep disturbances and depression, and discusses how light can be used as a non-pharmacological intervention to mitigate their negative effects. Bright days and dark nights are needed for health and well-being, but the present components of the built environment, especially those places where older adults spend most of their days, are too dimly illuminated during the day and too bright at night. To be effective light needs to be correctly specified, implemented and measured. Yet, without the appropriate specification and measurement of the stimulus, researchers will not be able to successfully demonstrate positive results in the field, nor will lighting designers and specifiers have the confidence to implement lighting solutions for promoting better sleep and mood in this population.

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The Role of Salivary Biomarkers in the Early Diagnosis of Alzheimer’s Disease and Parkinson’s Disease

Diagnostics ◽

10.3390/diagnostics11020371 ◽

2021 ◽

Vol 11 (2) ◽

pp. 371

Author(s):

Patrycja Pawlik ◽

Katarzyna Błochowiak

Keyword(s):

Alzheimer’S Disease ◽

Parkinson’S Disease ◽

Alzheimer's Disease ◽

Parkinson's Disease ◽

Early Diagnosis ◽

Neurodegenerative Diseases ◽

Diagnostic Tool ◽

Clinical Symptoms ◽

Early Screening ◽

Salivary Biomarkers

Many neurodegenerative diseases present with progressive neuronal degeneration, which can lead to cognitive and motor impairment. Early screening and diagnosis of neurodegenerative diseases such as Alzheimer’s disease (AD) and Parkinson’s disease (PD) are necessary to begin treatment before the onset of clinical symptoms and slow down the progression of the disease. Biomarkers have shown great potential as a diagnostic tool in the early diagnosis of many diseases, including AD and PD. However, screening for these biomarkers usually includes invasive, complex and expensive methods such as cerebrospinal fluid (CSF) sampling through a lumbar puncture. Researchers are continuously seeking to find a simpler and more reliable diagnostic tool that would be less invasive than CSF sampling. Saliva has been studied as a potential biological fluid that could be used in the diagnosis and early screening of neurodegenerative diseases. This review aims to provide an insight into the current literature concerning salivary biomarkers used in the diagnosis of AD and PD. The most commonly studied salivary biomarkers in AD are β-amyloid1-42/1-40 and TAU protein, as well as α-synuclein and protein deglycase (DJ-1) in PD. Studies continue to be conducted on this subject and researchers are attempting to find correlations between specific biomarkers and early clinical symptoms, which could be key in creating new treatments for patients before the onset of symptoms.

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Glia Not Neurons: Uncovering Brain Dysmaturation in a Rat Model of Alzheimer’s Disease

Biomedicines ◽

10.3390/biomedicines9070823 ◽

2021 ◽

Vol 9 (7) ◽

pp. 823

Author(s):

Ekaterina A. Rudnitskaya ◽

Tatiana A. Kozlova ◽

Alena O. Burnyasheva ◽

Natalia A. Stefanova ◽

Nataliya G. Kolosova

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Prefrontal Cortex ◽

Brain Structures ◽

Time Frame ◽

Oxys Rats ◽

Unknown Etiology ◽

Suitable Model ◽

Model Of Alzheimer’S Disease ◽

The Brain

Sporadic Alzheimer’s disease (AD) is a severe disorder of unknown etiology with no definite time frame of onset. Recent studies suggest that middle age is a critical period for the relevant pathological processes of AD. Nonetheless, sufficient data have accumulated supporting the hypothesis of “neurodevelopmental origin of neurodegenerative disorders”: prerequisites for neurodegeneration may occur during early brain development. Therefore, we investigated the development of the most AD-affected brain structures (hippocampus and prefrontal cortex) using an immunohistochemical approach in senescence-accelerated OXYS rats, which are considered a suitable model of the most common—sporadic—type of AD. We noticed an additional peak of neurogenesis, which coincides in time with the peak of apoptosis in the hippocampus of OXYS rats on postnatal day three. Besides, we showed signs of delayed migration of neurons to the prefrontal cortex as well as disturbances in astrocytic and microglial support of the hippocampus and prefrontal cortex during the first postnatal week. Altogether, our results point to dysmaturation during early development of the brain—especially insufficient glial support—as a possible “first hit” leading to neurodegenerative processes and AD pathology manifestation later in life.

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Rapid Universal Early Screening for Alzheimer's Disease and Related Dementia via Pattern Discovery in Diagnostic History

SSRN Electronic Journal ◽

10.2139/ssrn.3920640 ◽

2021 ◽

Author(s):

Dmytro Onishchenko ◽

Sam Searle ◽

Kenneth Rockwood ◽

James Mastrianni ◽

Ishanu Chattopadhyay

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Pattern Discovery ◽

Early Screening

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O3-11-05: Mitochondrial variation associated with decreased Alzheimer's disease incidence in the Cache County Study on Memory Health and Aging

Alzheimer s & Dementia ◽

10.1016/j.jalz.2012.05.1204 ◽

2012 ◽

Vol 8 (4S_Part_12) ◽

pp. P452-P452

Author(s):

Perry Ridge ◽

Taylor Maxwell ◽

Chris Corcoran ◽

JoAnn Tschanz ◽

Richard Cawthon ◽

...

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Disease Incidence ◽

Cache County

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Different Apathy Profile in Behavioral Variant of Frontotemporal Dementia and Alzheimer's Disease: A Preliminary Investigation

Current Gerontology and Geriatrics Research ◽

10.1155/2012/719250 ◽

2012 ◽

Vol 2012 ◽

pp. 1-8 ◽

Cited By ~ 20

Author(s):

Davide Quaranta ◽

Camillo Marra ◽

Concettina Rossi ◽

Guido Gainotti ◽

Carlo Masullo

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Frontotemporal Dementia ◽

Sleep Disturbances ◽

Preliminary Investigation ◽

Univariate Analysis ◽

Behavioral Changes ◽

Neuropsychiatric Inventory ◽

Multivariate Logistic Regression ◽

Clinical Expression

Apathy is one of the most common behavioral symptoms of dementia; it is one of the salient features of behavioral variant of frontotemporal dementia (bvFTD) but is also very frequent in Alzheimer's disease. This preliminary investigation was aimed at assessing the type of apathy-related symptoms in a population of bvFTD and AD subjects showing comparable apathy severity. Each patient underwent a comprehensive neuropsychological assessment; behavioral changes were investigated by the neuropsychiatric inventory (NPI), using the NPI-apathy subscale to detect apathetic symptoms. At univariate analysis, bvFTD subjects showed lack of initiation (χ2=4.602,p=0.032), reduced emotional output (χ2=6.493,p=0.008), and reduced interest toward friends and family members (χ2=4.898,p=0.027), more frequently than AD subjects. BvFTD displayed higher scores than AD on NPI total score (p=0.005) and on subscales assessing agitation (p=0.004), disinhibition (p=0.007) and sleep disturbances (p=0.025); conversely, AD subjects were more impaired on memory, constructional abilities, and attention. On multivariate logistic regression, reduced emotional output was highly predictive of bvFTD (OR=18.266;p=0.008). Our preliminary findings support the hypothesis that apathy is a complex phenomenon, whose clinical expression is conditioned by the site of anatomical damage. Furthermore, apathy profile may help in differentiating bvFTD from AD.

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