scholarly journals Neuropsychological and neuroimaging changes in preclinical Alzheimer's disease

2006 ◽  
Vol 12 (5) ◽  
pp. 707-735 ◽  
Author(s):  
ELIZABETH W. TWAMLEY ◽  
SUSAN A. LEGENDRE ROPACKI ◽  
MARK W. BONDI
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Functional Neuroimaging ◽  
Neuropsychological Functioning ◽  
Clinical Manifestations ◽  
Symptomatic Treatment ◽  
Cross Sectional ◽  
Preclinical Ad ◽  
Normal Individuals

Alzheimer's disease (AD) is a common, devastating form of dementia. With the advent of promising symptomatic treatment, the importance of recognizing AD at its very earliest stages has increased. We review the extant neuropsychological and neuroimaging literature on preclinical AD, focusing on longitudinal studies of initially nondemented individuals and cross-sectional investigations comparing at-risk with normal individuals. We systematically reviewed 91 studies of neuropsychological functioning, structural neuroimaging, or functional neuroimaging in preclinical AD. The neuropsychological studies indicated that preclinical AD might be characterized by subtle deficits in a broad range of neuropsychological domains, particularly in attention, learning and memory, executive functioning, processing speed, and language. Recent findings from neuroimaging research suggest that volume loss and cerebral blood flow or metabolic changes, particularly in the temporal lobe, may be detected before the onset of dementia. There exist several markers of a preclinical period of AD, in which specific cognitive and biochemical changes precede the clinical manifestations. The preclinical indicators of AD reflect early compromise of generalized brain integrity and temporal lobe functioning in particular. (JINS, 2006,12, 707–735.)

Identification of a Pathogenic PSEN1 Ala285Val Mutation Associated with Early-Onset Alzheimer’s Disease

2020 ◽  
Vol 17 (5) ◽  
pp. 438-445
Author(s):  
Van Giau Vo ◽  
Jung-Min Pyun ◽  
Eva Bagyinszky ◽  
Seong S.A. An ◽  
Sang Y. Kim
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Early Onset ◽  
Parietal Lobe ◽  
Disease Diagnosis ◽  
Random Coil ◽  
Magnetic Resonance Imaging Scan ◽  
Preclinical Ad ◽  
Early Onset Alzheimer’S Disease

Background: Presenilin 1 (PSEN1) was suggested as the most common causative gene of early onset Alzheimer’s Disease (AD). Methods: Patient who presented progressive memory decline in her 40s was enrolled in this study. A broad battery of neuropsychological tests and neuroimaging was applied to make the diagnosis. Genetic tests were performed in the patient to evaluate possible mutations using whole exome sequencing. The pathogenic nature of missense mutation and its 3D protein structure prediction were performed by in silico prediction programs. Results: A pathogenic mutation in PSEN1 (NM_000021.3: c.1027T>C p.Ala285Val), which was found in a Korean EOAD patient. Magnetic resonance imaging scan showed mild left temporal lobe atrophy. Hypometabolism appeared through 18F-fludeoxyglucose Positron Emission Tomography (FDG-PET) scanning in bilateral temporal and parietal lobe, and 18F-Florbetaben-PET (FBB-PET) showed increased amyloid deposition in bilateral frontal, parietal, temporal lobe and hence presumed preclinical AD. Protein modeling showed that the p.Ala285Val is located in the random coil region and could result in extra stress in this region, resulting in the replacement of an alanine residue with a valine. This prediction was confirmed previous in vitro studies that the p.Trp165Cys resulted in an elevated Aβ42/Aβ40 ratio in both COS-1 and HEK293 cell lines compared that of wild-type control. Conclusion: Together, the clinical characteristics and the effect of the mutation would facilitate our understanding of PSEN1 in AD pathogenesis for the disease diagnosis and treatment. Future in vivo study is needed to evaluate the role of PSEN1 p.Ala285Val mutation in AD progression.

scholarly journals Medial Temporal Lobe Subregional Atrophy in Aging and Alzheimer's Disease: A Longitudinal Study

2021 ◽  
Vol 13 ◽  
Author(s):  
Léa Chauveau ◽  
Elizabeth Kuhn ◽  
Cassandre Palix ◽  
Francesca Felisatti ◽  
Valentin Ourry ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Adult Lifespan ◽  
Parahippocampal Cortex ◽  
Age Related ◽  
Preclinical Ad ◽  
Brodmann Areas ◽  
Over Time

Medial temporal lobe (MTL) atrophy is a key feature of Alzheimer's disease (AD), however, it also occurs in typical aging. To enhance the clinical utility of this biomarker, we need to better understand the differential effects of age and AD by encompassing the full AD-continuum from cognitively unimpaired (CU) to dementia, including all MTL subregions with up-to-date approaches and using longitudinal designs to assess atrophy more sensitively. Age-related trajectories were estimated using the best-fitted polynomials in 209 CU adults (aged 19–85). Changes related to AD were investigated among amyloid-negative (Aβ−) (n = 46) and amyloid-positive (Aβ+) (n = 14) CU, Aβ+ patients with mild cognitive impairment (MCI) (n = 33) and AD (n = 31). Nineteen MCI-to-AD converters were also compared with 34 non-converters. Relationships with cognitive functioning were evaluated in 63 Aβ+ MCI and AD patients. All participants were followed up to 47 months. MTL subregions, namely, the anterior and posterior hippocampus (aHPC/pHPC), entorhinal cortex (ERC), Brodmann areas (BA) 35 and 36 [as perirhinal cortex (PRC) substructures], and parahippocampal cortex (PHC), were segmented from a T1-weighted MRI using a new longitudinal pipeline (LASHiS). Statistical analyses were performed using mixed models. Adult lifespan models highlighted both linear (PRC, BA35, BA36, PHC) and nonlinear (HPC, aHPC, pHPC, ERC) trajectories. Group comparisons showed reduced baseline volumes and steeper volume declines over time for most of the MTL subregions in Aβ+ MCI and AD patients compared to Aβ− CU, but no differences between Aβ− and Aβ+ CU or between Aβ+ MCI and AD patients (except in ERC). Over time, MCI-to-AD converters exhibited a greater volume decline than non-converters in HPC, aHPC, and pHPC. Most of the MTL subregions were related to episodic memory performances but not to executive functioning or speed processing. Overall, these results emphasize the benefits of studying MTL subregions to distinguish age-related changes from AD. Interestingly, MTL subregions are unequally vulnerable to aging, and those displaying non-linear age-trajectories, while not damaged in preclinical AD (Aβ+ CU), were particularly affected from the prodromal stage (Aβ+ MCI). This volume decline in hippocampal substructures might also provide information regarding the conversion from MCI to AD-dementia. All together, these findings provide new insights into MTL alterations, which are crucial for AD-biomarkers definition.

scholarly journals Falls Associate with Neurodegenerative Changes in ATN Framework of Alzheimer’s Disease

2020 ◽  
Vol 77 (2) ◽  
pp. 745-752
Author(s):  
Audrey Keleman ◽  
Julie K. Wisch ◽  
Rebecca M. Bollinger ◽  
Elizabeth A. Grant ◽  
Tammie L. Benzinger ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Brain Connectivity ◽  
Hippocampal Volume ◽  
Cross Sectional Study ◽  
Amyloid Pet ◽  
Resting State Functional Connectivity ◽  
Cross Sectional ◽  
Preclinical Ad ◽  
Amyloid Accumulation

Background: Behavioral markers for Alzheimer’s disease (AD) are not included within the widely used amyloid-tau-neurodegeneration framework. Objective: To determine when falls occur among cognitively normal (CN) individuals with and without preclinical AD. Methods: This cross-sectional study recorded falls among CN participants (n = 83) over a 1-year period. Tailored calendar journals recorded falls. Biomarkers including amyloid positron emission tomography (PET) and structural and functional magnetic resonance imaging were acquired within 2 years of fall evaluations. CN participants were dichotomized by amyloid PET (using standard cutoffs). Differences in amyloid accumulation, global resting state functional connectivity (rs-fc) intra-network signature, and hippocampal volume were compared between individuals who did and did not fall using Wilcoxon rank sum tests. Among preclinical AD participants (amyloid-positive), the partial correlation between amyloid accumulation and global rs-fc intra-network signature was compared for those who did and did not fall. Results: Participants who fell had smaller hippocampal volumes (p = 0.04). Among preclinical AD participants, those who fell had a negative correlation between amyloid uptake and global rs-fc intra-network signature (R = –0.75, p = 0.012). A trend level positive correlation was observed between amyloid uptake and global rs-fc intra-network signature (R = 0.70, p = 0.081) for preclinical AD participants who did not fall. Conclusion: Falls in CN older adults correlate with neurodegeneration biomarkers. Participants without falls had lower amyloid deposition and preserved global rs-fc intra-network signature. Falls most strongly correlated with presence of amyloid and loss of brain connectivity and occurred in later stages of preclinical AD.

scholarly journals Associations of AT(N) biomarkers with neuropsychiatric symptoms in preclinical Alzheimer’s disease and cognitively unimpaired individuals

2021 ◽  
Vol 10 (1) ◽  
Author(s):  
Kok Pin Ng ◽  
Hui Chiew ◽  
Pedro Rosa-Neto ◽  
Nagaendran Kandiah ◽  
Zahinoor Ismail ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cognitive Decline ◽  
Longitudinal Studies ◽  
Neuropsychiatric Symptoms ◽  
Amyloid Β ◽  
Cross Sectional ◽  
Preclinical Ad ◽  
Cross Sectional Studies

AbstractThe development of in vivo biomarkers of Alzheimer’s disease (AD) has advanced the diagnosis of AD from a clinical syndrome to a biological construct. The preclinical stage of AD continuum is defined by the identification of AD biomarkers crossing the pathological threshold in cognitively unimpaired individuals. While neuropsychiatric symptoms (NPS) are non-cognitive symptoms that are increasingly recognized as early manifestations of AD, the associations of NPS with AD pathophysiology in preclinical AD remain unclear. Here, we review the associations between NPS and AD biomarkers amyloid-β (Aβ), tau and neurodegeneration in preclinical AD and cognitively-unimpaired individuals in 19 eligible English-language publications (8 cross-sectional studies, 10 longitudinal, 1 both cross-sectional and longitudinal). The cross-sectional studies have consistently shown that NPS, particularly depressive and anxiety symptoms, are associated with higher Aβ. The longitudinal studies have suggested that greater NPS are associated with higher Aβ and cognitive decline in cognitively unimpaired subjects over time. However, most of the studies have either cross-sectionally or longitudinally shown no association between NPS and tau pathology. For the association of NPS and neurodegeneration, two studies have shown that the cerebrospinal fluid total-tau is linked to longitudinal increase in NPS and that the NPS may predict longitudinal metabolic decline in preclinical AD, respectively. However, evidence for the association between atrophy and NPS in preclinical AD is less consistent. Therefore, future longitudinal studies with well-designed methodologies and NPS measurements are required not only to determine the relationship among AT(N) biomarkers, NPS and cognitive decline, but also to elucidate the contribution of comorbid pathology to preclinical AD.

scholarly journals Complexity Measures for Quantifying Changes in Electroencephalogram in Alzheimer’s Disease

Complexity ◽  
2018 ◽  
Vol 2018 ◽  
pp. 1-12 ◽  
Author(s):  
Ali H. Husseen Al-Nuaimi ◽  
Emmanuel Jammeh ◽  
Lingfen Sun ◽  
Emmanuel Ifeachor
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Early Diagnosis ◽  
Clinical Manifestations ◽  
Quantitative Measure ◽  
Complexity Measures ◽  
Cross Sectional ◽  
Frequency Bands ◽  
Brain Functions ◽  
Early Stages

Alzheimer’s disease (AD) is a progressive disorder that affects cognitive brain functions and starts many years before its clinical manifestations. A biomarker that provides a quantitative measure of changes in the brain due to AD in the early stages would be useful for early diagnosis of AD, but this would involve dealing with large numbers of people because up to 50% of dementia sufferers do not receive formal diagnosis. Thus, there is a need for accurate, low-cost, and easy to use biomarkers that could be used to detect AD in its early stages. Potentially, electroencephalogram (EEG) based biomarkers can play a vital role in early diagnosis of AD as they can fulfill these needs. This is a cross-sectional study that aims to demonstrate the usefulness of EEG complexity measures in early AD diagnosis. We have focused on the three complexity methods which have shown the greatest promise in the detection of AD, Tsallis entropy (TsEn), Higuchi Fractal Dimension (HFD), and Lempel-Ziv complexity (LZC) methods. Unlike previous approaches, in this study, the complexity measures are derived from EEG frequency bands (instead of the entire EEG) as EEG activities have significant association with AD and this has led to enhanced performance. The results show that AD patients have significantly lower TsEn, HFD, and LZC values for specific EEG frequency bands and for specific EEG channels and that this information can be used to detect AD with a sensitivity and specificity of more than 90%.

scholarly journals Plasma p-Tau181 Outperforms Cerebrospinal Fluid Total Tau in Terms of Alzheimer’s Disease Diagnosis

2021 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Mohammad Balabandian ◽  
Mohammad Reza Rostami ◽  
Richard T. Ward ◽  
Niloufar Ahmadi ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Cerebrospinal Fluid ◽  
Structural Changes ◽  
Clinical Symptoms ◽  
Disease Diagnosis ◽  
Cross Sectional ◽  
Total Tau ◽  
Preclinical Ad ◽  
Brain Changes

Abstract Alzheimer's disease (AD) is a progressive neurodegenerative disease associated with dementia, and is a serious concern for the health of individuals and government health care systems worldwide. Gray matter atrophy and white matter damage are major contributors to cognitive deficits experienced by patients with AD, as seen through magnetic resonance imaging (MRI). Many of these brain changes associated with AD begin to occur about 15 years before the onset of initial clinical symptoms. Therefore, it is critical to find biomarkers reflective of these brain changes associated with AD to identify this disease and monitor its prognosis and development. The level of hyperphosphorylated tau 181 (p-Tau181) in the plasma has been recently considered as a novel biomarker for the presence of AD, with increased levels in patients with AD, preclinical AD, and those experiencing mild cognitive impairment (MCI). In the current study, we examined the association of cerebrospinal fluid (CSF) and plasma levels of p-Tau181 with structural brain changes pertaining to cortical thickness, cortical volume, surface area, and subcortical volume in MCI patients. In this cross-sectional study we included the information of 461 MCI patients from the Alzheimer's Disease Neuroimaging Initiative (ADNI) cohort. The results of voxel-wise partial correlation analyses showed a significant negative correlation between the increased levels of plasma p-Tau181, CSF total tau, and CSF p-Tau181 and structural changes in widespread brain regions. These results provide evidence for the use of plasma p-Tau181 as a diagnostic marker for structural changes in the brain associated with the early stages of AD and neurodegeneration.

scholarly journals THE ACCURACY OF TRANSCRANIAL SONOGRAPHY ON ALZHEIMER’S DISEASE DIAGNOSIS

2021 ◽  
Author(s):  
Roberto Santos ◽  
Rita Fernandes
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Temporal Lobe ◽  
Medial Temporal Lobe ◽  
Disease Diagnosis ◽  
Transcranial Sonography ◽  
University Hospital ◽  
Healthy Controls ◽  
Cross Sectional ◽  
Outpatient Unit

Background: The diagnosis of Alzheimer’s disease (AD) is clinical, combining neurological examination, neuropsychological tests and neuroimaging. One of the anatomical features of AD is medial temporal lobe (MTL) atrophy graduated by magnetic resonance imaging (MRI) with accuracy to discriminate between healthy controls, mild neurocognitive disorder (MCI) or dementia, but it has its limitations. Transcranial sonography (TCS) demonstrated good accuracy to display changes in echogenicity or size of intracranial structures. Objective: The objective of this study is to evaluate TCS diagnostic accuracy in AD. Methods: Prospective cross-sectional case-control study. Patients in the outpatient unit of a University Hospital with >2 y AD diagnosis and controls. TCS performed with a 2-4MHz sector probe to study lateral temporal lobe (A), MTL height (B) and width (C), ambiens cistern width (D) and choroidal cistern height (E). Results: TCCS exams were performed. 2 individuals had no bone window (1 control, 1 AD). 15 healthy controls and 4 DA patients showed significantly different B/E measurements (3.17+0,47 cm2 vs 2.23+0.22 cm2; p=0,0001). Conclusions: Our preliminary results indicate that our measurements are in agreement with those found in the literature. The present results indicate the reproducibility of the technique in our Hospital and encourages us to expand the number of participants.

scholarly journals Nutrient intake and brain biomarkers of Alzheimer's disease in at-risk cognitively normal individuals: a cross-sectional neuroimaging pilot study

BMJ Open ◽  
2014 ◽  
Vol 4 (6) ◽  
pp. e004850-e004850 ◽  
Author(s):  
L. Mosconi ◽  
J. Murray ◽  
M. Davies ◽  
S. Williams ◽  
E. Pirraglia ◽  
...  
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
At Risk ◽  
Pilot Study ◽  
Nutrient Intake ◽  
Cross Sectional ◽  
Cognitively Normal ◽  
Normal Individuals

scholarly journals CSF total tau, plasma and CSF p tau 181 associated with structural changes in the early stage of Alzheimer's disease

2020 ◽  
Author(s):  
Fardin Nabizadeh ◽  
Mohammad Reza Rostami ◽  
mohammad Balabandian ◽  
Niloufar Ahmadi
Keyword(s):  
Alzheimer’S Disease ◽  
Alzheimer's Disease ◽  
Structural Changes ◽  
Clinical Symptoms ◽  
Early Stage ◽  
Cross Sectional ◽  
Total Tau ◽  
Preclinical Ad ◽  
The Brain

Abstract Alzheimer's disease (AD) is the most important cause of dementia and is a serious concern for individuals and governments worldwide. Changes in the brain appear about 15 years before the first clinical symptoms; with this in mind, it can clear the role of biomarkers in monitoring Alzheimer's development. P tau 181 level in plasma recently emerged as a new biomarker and rises obviously in AD patients, preclinical AD, and MCI patients. The role of gray matter atrophy and white matter damages in cognitive decline is well established, which is detectable by magnetic resonance imaging (MRI). In this investigation, we measured the association between CSF (total tau, and p tau 181) and plasma p tau 181 with structural changes (cortical thickness, cortical volume, surface area, and subcortical volume) in MCI patients. We performed a cross-sectional study on the ADNI cohort between 461 MCI patients. Results of voxel-wise partial correlation analysis in our participants showed a significant correlation between plasma p tau 181, CSF total tau and p tau 181 with changes in structural values in different regions. Our study revealed a significant correlation between plasma p tau and structural changes in the brain regions associated with Alzheimer's disease physiopathology. These results provide evidence for using plasma p tau 181 as a diagnostic factor in the early onset of AD patients and neurodegeneration.

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