Neuropathology and Cognitive Impairment in Alzheimer Disease: A Complex but Coherent Relationship

Abstract

Amyloid plaques and neurofibrillary tangles (NFTs) are the pathological hallmarks of Alzheimer disease (AD). There is controversy regarding the use of current diagnostic criteria for AD and whether amyloid plaques and NFTs contribute to cognitive impairment. Because AD is specific to humans, rigorous and comprehensive clinicopathologic studies are necessary to test and refine hypotheses of AD diagnosis and pathogenesis. Neither the clinical nor the pathological aspects of AD evolve in a linear manner, but the predictable sequence of AD pathology allows for stage-based correlations with cognitive deterioration. We discuss subsets of patients with clinical dementia who lack amyloid plaques and NFTs and, conversely, whether individuals without antemortem cognitive impairment can harbor severe AD-type pathological findings at autopsy. There are many medical, technical, and anatomical challenges to clinicopathologic studies in AD. For example, at least two thirds of persons older than 80 years have non-AD brain diseases that can effect on cognitive function. We argue that existing data strongly support the hypothesis that both amyloid plaques and NFTs contribute to cognitive impairment.

Cortical phase changes in Alzheimer's disease at 7T MRI: A novel imaging marker

“…Moreover, the value of our method should be investigated in the preclinical stages of AD. Therefore, in future studies we aim to study cortical phase changes in patients with mild cognitive impairment to evaluate the possibility of detecting early AD pathology and to evaluate the use of these cortical phase changes as an early treatment marker because the biological activity has already peaked before the symptomatic stage [1]. In addition, future studies should address translational research from 7T to 3T MRI to investigate whether our method could be used on 3T MRI data because 7T MRI is not widely available.…”

“…Currently, because of the absence of validated sensitive and specific tests, the clinical diagnosis of AD can only be made at a late stage of disease progression and with a considerable degree of uncertainty-probable AD, at best-and is based on criteria from the Diagnostic and Statistical Manual of Mental Disorders, 4th edition, and the National Institute of Neurological, Communicative Disorders and Stroke-Alzheimer's Disease and Related Disorders Association. Nevertheless, the histological hallmarks of AD pathology, comprising amyloid plaques and neurofibrillary tangles, are known to occur up to 10 to 20 years before the objective detection of cognitive decline [1]. Recently, positron emission tomography (PET) using Pittsburgh compound B (PiB) has been introduced as a diagnostic tool to detect cerebral amyloid in vivo [2][3][4][5][6][7][8].…”

Vieillissement, cognition et perspectives de prévention

“…La maladie clinique n'apparaît que lorsque l'équilibre entre l'étendue et les effets des lésions et les capacités d'adaptation ou de compensation est rompu [3]. Cela explique, par exemple, qu'un grand nombre de sujets porteurs des lésions importantes de maladie d'Alzheimer dans le cerveau à l'autopsie ne présentaient pas de leur vivant de manifestations cliniques de la maladie [6] ; probablement parce que leurs capacités d'adaptation leur permettaient de compenser les effets de ces lésions. Ces capacités d'adaptation et de compensation sont constituées et entretenues tout au long de la vie.…”

Cognitive reserve: the evolution of the conceptual framework

“…It is a neurodegenerative disorder that typically presents with an isolated memory deficit, followed by a progressive accumulation of cognitive disabilities until conversion to dementia [1]. However, it is becoming increasingly clearer that there is a non-linear relationship between the extent of brain tissue damage and the resulting patients' clinical outcome [2,3].…”

“…Alzheimer's disease (AD) is the most common cause of cognitive decline in west world's population [1]. It is a neurodegenerative disorder that typically presents with an isolated memory deficit, followed by a progressive accumulation of cognitive disabilities until conversion to dementia [1].…”