Working memory in early Alzheimer's disease: a neuropsychological review

Abstract

Background: Reports of the extent of working memory (WM) impairment in early Alzheimer's disease (AD) have been inconsistent. Using the model of WM proposed by Baddeley, neuropsychological evidence for the impairment of WM in early AD is evaluated. Method: Literature searches were performed using Medline, PsycINFO and Embase databases. Individual papers were then examined for additional references not revealed by computerised searches. Results: Phonological loop function is intact at the preclinical and early stages of AD, becoming more impaired as the disease progresses. In mild AD, there is impairment on tasks assessing visuospatial sketchpad (VSS) function; however, these tasks also require executive processing by the central executive system (CES). There is evidence that the CES is impaired in mild AD and may be affected in the earlier preclinical stage of the disease. Episodic buffer function may be impaired but further research is required. Conclusions: Future research into central executive functioning at the earliest stages of the disease, combined with further longitudinal studies, needs to be carried out. Tasks to assess the proposed functions of the episodic buffer and specific tests of the VSS suitable for AD subjects need to be developed and validated. Learning more about these processes and how they are affected in AD is important in understanding and managing the cognitive deficits seen in the early stages of AD.

GOOD or BAD Responder? Behavioural and Neuroanatomical Markers of Clinical Response to Donepezil in Dementia

“…These differences at T1 should most likely testify fairly different trajectories in the disease progression (see also Clearly, behind the overall cognitive decline measured by a very popular but rather crude index like the MMSE, a more complex pattern is hidden. In particular, the tests where most of the BAD-responders showed a time-related decline were those tackling executive functions [47], a finding consistent with what is described as the typical progression of the disease [48][49][50][51][52]. Thus, although the use of the MMSE test to monitor the disease progression has the natural charm of the simplicity involved in both test administration and test scoring, it is clear that one could achieve a more detailed description of the neuropsychological trajectories associated with the disease by using a more extensive neuropsychological test battery.…”

Bridging Integrator 1 (BIN1) Genotype Effects on Working Memory, Hippocampal Volume, and Functional Connectivity in Young Healthy Individuals

“…Although early and significant episodic memory impairment constitutes the clinical core diagnostic criterion of AD (Dubois et al, 2014), there is increasing evidence of early deficits in WM and executive function in patients with MCI and AD (Crawford et al, 2013;Gagnon and Belleville, 2011;Huntley and Howard, 2010;Kessels et al, 2011;Koppel et al, 2014). Moreover, fMRI studies have also suggested a possible subclinical impairment of WM capacity in healthy APOE ε4 carriers (Chen et al, 2013).…”

“…Although deficits in episodic memory characterize AD, there is increasing evidence that working memory (WM), which involves the short-term online storage and manipulation of information, is also impaired during the earliest stages of disease (Huntley and Howard, 2010). Deficits in WM have also been demonstrated using specialized testing in APOE ε4 carriers (Rosen et al, 2002).…”

Prefrontal cortical mechanisms underlying delayed alternation in mice

“…Abnormalities in PFC circuitry have long been associated with psychiatric disorders such as schizophrenia and neurodegenerative diseases such as Alzheimer's disease (Cole et al 2011;Fernando and Robbins 2011;Goldman-Rakic and Selemon 1997;Huntley and Howard 2010;Insel and Fernald 2004;Sigurdsson et al 2010). In recent years, the mouse has become a major model organism for the study of such disorders in particular and of cognition and behavior in general, and these mouse models provide powerful genetic tools that allow us to dissect the underlying molecular, cellular, and circuit mechanisms.…”