Diagnosis and Treatment of Alzheimer’s Disease:

Abstract

Finding earlier and more definitive ways to diagnose AD has been the subject of significant amounts of research, and testing advances have been seen in the last decade with expanded use of positron emission tomography (PET) and magnetic resonance imaging (MRI), as well as in the identification of biomarkers in cerebrospinal fluid (CSF) and more recently serum. While limited, some of these diagnostic advances are available to the public, though typically at a high price.A high-level overview of emerging diagnostic strategies can be found below. Volumetric DataIn simple terms, volume changes in specific brain regions can predict the likelihood of progression from mild cognitive impairment (MCI) to AD. These volume assessments can be done by radiologists or with the help of FDA-approved MRI volumetric data software packages such as Neuroquant and Neuoreader. Hippocampal volume changes in particular are regarded as an important AD biomarker. 3 Because of limited sensitivity of this measure in diagnosing AD, however, MRI studies are regarded as a contributor to the diagnostic process but not sufficient in themselves for determining a diagnosis. 4 Diffusion Tensor ImagingDiffusion Tensor Imaging (DTI) is an advanced neuroimaging technique that uses the diffusion properties of water molecules to generate magnetic resonance images that correspond to changes in macroscopic axonal organization. This technique can be used to evaluate the structure of vertical cellular micro-circuits, termed "minicolumns." Previous studies have demonstrated that minicolumns are known to be altered in a somewhat predictable and progressive manner during aging, MCI, and AD. 5 Additionally, pathologic changes of cortex columnar architecture are associated with increased plaque load and cognitive decline. 6 With the aid of proprietary software, DTI can be measured and used as a marker of neurodegeneration. PET ScanPathologic species of two proteins, amyloid-β (Aβ) and hyperphosphorylated tau accumulate in the brains of persons with AD. PET scans are able to assess for both proteins and serve as a reliable biomarker. Amyloid accumulation precedes clinically significant cognitive changes and tau accumulation progresses in step with cognitive decline, suggesting the value of PET scans for diagnosis and measurement of disease progression. 7 CSF and Blood TestsCerebrospinal fluid (CSF), accessible through lumbar puncture, surrounds the brain. Changes in the levels of Aβ and tau proteins in the CSF develop decades before the onset of clinically significant AD. 8 Among the tests of CSF developed during recent decades, the most prominent are CSF Aβ42:Aβ40 ratio and the CSF tau phosphorylated at threonine 181 (P-tau181). CSF P-tau217, measurable in the peripheral circulation, is hoped to provide a biomarker with very high sensitivity and specificity. 9Because blood is more easily accessed than CSF, C2N Diagnostics in St. Louis, Missouri has developed and released a blood test called PrecivityAD which is available in most of the U.S. and to the European U...

A Review of ApoE4 Interference Targeting Mitophagy Molecular Pathways for Alzheimer's Disease

“…APOE ε4 allele, usually existing in approximately 15% of people, lowers the age of AD onset and increases the risk of AD in a dose-dependent manner (Levy et al, 1990 ; Wallon et al, 2012 ; Ward et al, 2012 ; Tang et al, 2016 ). Accumulating difficulties remain when Aβ-targeting interference fails to effectively halt or slow clinical AD progression (Bohrmann et al, 2012 ; Salloway et al, 2014 ; Bomasang-Layno and Bronsther, 2021 ; Pleen and Townley, 2022 ); thus, it is widely believed that amyloid cascading seems to appear as less possibility for a major explanation of AD pathogenesis. Other rising insights draw more and more interests broadly.…”

Analysis of treatment pattern of anti-dementia medications in newly diagnosed Alzheimer’s dementia using OMOP CDM

“…5 ). This trend might be related to the treatment guidelines for AD 25 , 26 as well as the reimbursement criteria of the Korean National Health Insurance 24 . Previous meta-analyses have revealed that AChEIs delay cognitive dysfunction and decline in performance of daily activities for 6–12 months on average and slow the decline in global clinical dementia rating 27 , 28 ; therefore, they are recommended for use from the initial stages of AD 29 , 30 .…”

Apoe as a Risk Factor for Alzheimer's Disease and Lipid Metabolism Disorders: Molecular Analysis

“…Type III hyperlipoproteinemia, also called familial hypercholesterolemia, is a rare type of mixed hyperlipidemia in which cholesterol and triglyceride levels are above the normal value [2,7]. The disease may be associated with mutations in two places of the APOE gene, which are inherited in an autosomal recessive manner and lead to impaired fat metabolism [19].…”

“…It is most often diagnosed in people over the age of 65, but also in younger individuals [1]. Characteristic symptoms of the disease include memory loss, difficulties in everyday activities, disorientation, problems with concentration and spatial orientation, and many other disorders related to the improper functioning of the brain [2]. According to the Institute for Health Metrics and Evaluations (IHME), in Poland in 2019, the estimated percentage of people suffering from Alzheimer's disease and related diseases was 1.5% (585,000 people), which was 0.2 percent higher than in 2014.…”