The Neuropsychological Profile of Alzheimer Disease

Abstract

Neuropsychological assessment has featured prominently over the past 30 years in the characterization of dementia associated with Alzheimer disease (AD). Clinical neuropsychological methods have identified the earliest, most definitive cognitive and behavioral symptoms of illness, contributing to the identification, staging, and tracking of disease. With increasing public awareness of dementia, disease detection has moved to earlier stages of illness, at a time when deficits are both behaviorally and pathologically selective. For reasons that are not well understood, early AD pathology frequently targets large-scale neuroanatomical networks for episodic memory before other networks that subserve language, attention, executive functions, and visuospatial abilities. This chapter reviews the pathognomonic neuropsychological features of AD dementia and how these differ from "normal," age-related cognitive decline and from other neurodegenerative diseases that cause dementia, including cortical Lewy body disease, frontotemporal lobar degeneration, and cerebrovascular disease.O ver the past 30 years, neuropsychological assessment has featured centrally in characterizing the dementia associated with Alzheimer disease (AD), identifying the most salient and earliest cognitive and behavioral symptoms and contributing to the staging and tracking of disease (Flicker et al. 1984;Morris et al. 1989;Storandt and Hill 1989;Storandt 1991;Welsh et al. 1991Welsh et al. , 1992Locascio et al. 1995;Albert 1996;Storandt et al. 1998; see also Salmon and Bondi 2009). As research has increasingly focused on earlier stages of illness, it has become clear that biological markers of AD can precede cognitive and behavioral symptoms by years. It has also become clear that the early symptoms of AD represent the selective targeting by disease of specific, "largescale" neuroanatomical networks, with clinical deficits consistent with the anatomical locus of impact (Weintraub and Mesulam 1993Seeley et al. 2009). In the usual case, AD pathology is initially selective for limbic regions that subserve episodic memory, which leads to a circumscribed memory deficit in the early stages of the disease (Braak and Braak 1991;Jack et al. 1997; de ToledoMorrell et al. 2000). It is only as pathology progresses to other neocortical regions over time (Braak and Braak 1996a,b;Braak et al. 1999;Jack et al. 2000) that additional cognitive symptoms emerge and the full dementia syndrome becomes apparent.These discoveries have prompted a revision of the established research diagnostic criteria for AD dementia that had served so well since 1984 (McKhann et al. 1984). The new criteria define not only the dementia of AD (McKhann et al. 2011) but also incorporate a fuller spectrum of cognitive aging, including an intermediate stage of mild cognitive impairment (MCI) that precedes the dementia (Albert et al. 2011). A third, even earlier, stage of "preclinical AD" has also been identified (Sperling et al. 2011). This prodromal period is characterized by the presence of bi...

Lipocalin 2 modulates the cellular response to amyloid beta

“…31 Thus, produced in response to Ab , LCN2 can regulate important mechanisms and pathways that are critical for brain cell activation 31,32 and that may ultimately lead to alterations in brain areas involved in cognition and memory, which are affected in AD. 46 In agreement, patients with mild cognitive impairment present high levels of LCN2 in the plasma 47 and low levels of LCN2 in the CSF, 8 which points to an imbalance of LCN2 levels in the brain in the early phases of dementia. It is clear, thus, that the role of LCN2 in neurodegenerative disorders such as AD warrants further investigation.…”

Memory retrieval by activating engram cells in mouse models of early Alzheimer’s disease

“…In the literature 9 , it is widely recognized that early AD patients exhibit non-episodic memory deficits as well, which would involve brain structures other than the MTL. Additional work is required to examine mechanisms underlying cognitive impairments in these other types of memories.…”

“…The underlying mechanism of memory failure in early AD patients may not necessarily parallel the molecular and circuit impairments observed in mouse models of early AD. For instance, some early AD patients can exhibit amyloid plaque deposition years before the onset of cognitive decline 9 . However, converging data on the underlying mechanism for genetically-and pharmacologicallyinduced amnesia in animal models increase the possibility that similar memory retrievalbased failures may also operate in an early stage of AD patients.…”

Mild cognitive impairment and progression to dementia of Alzheimer's disease

“…18 progression to ad (figure 2) 19 Several authors observed an increased rate of progression toward dementia in patients with MCI. 8,[20][21][22][23][24][25] However, studies have not been replicated by other researchers. One explanation for this fact may arise from the observation that memory complaints appear to have little correlation with the performance of individuals on objective cognitive tests.…”