Limited Longitudinal Change in Self-reported Spatial Navigation Ability in Preclinical Alzheimer Disease

AbstractCognitive measures that are sensitive to biological markers of Alzheimer disease (AD) pathology are needed to (a) facilitate preclinical staging, (b) identify individuals who are at the highest risk for developing clinical symptoms, and (c) serve as endpoints for evaluating the efficacy of interventions. The present study assesses the utility of two cognitive composite scores of attentional control and episodic memory as markers for preclinical AD pathology in a group of cognitively normal older adults (N=238), as part of the Adult Children Study. All participants were given a baseline cognitive assessment and follow-up assessments every 3 years over an 8-year period, as well as a lumbar puncture within 2 years of the initial assessment to collect cerebrospinal fluid (CSF) and amyloid tracer Pittsburgh compound-B scan for amyloid imaging. Results indicated that attentional control was correlated with levels of Aβ42 at the initial assessment whereas episodic memory was not. Longitudinally, individuals with high CSF tau exhibited a decline in both attention and episodic memory over the course of the study. These results indicate that measures of attentional control and episodic memory can be used to evaluate cognitive decline in preclinical AD and provide support that CSF tau may be a key mechanism driving longitudinal cognitive change. (JINS, 2015, 21, 573–583)

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Developing a Spatial Navigation Screening Tool Sensitive to the Preclinical Alzheimer Disease Continuum

Archives of Clinical Neuropsychology ◽

10.1093/arclin/acz019 ◽

2019 ◽

Vol 34 (7) ◽

pp. 1138-1155 ◽

Cited By ~ 1

Author(s):

Samantha L Allison ◽

Thomas L Rodebaugh ◽

Chiharu Johnston ◽

Anne M Fagan ◽

John C Morris ◽

...

Keyword(s):

Alzheimer Disease ◽

Psychometric Properties ◽

Cognitive Mapping ◽

Spatial Navigation ◽

Intraclass Correlation ◽

Self Report ◽

Screening Tools ◽

Screening Measure ◽

Preclinical Ad ◽

Mapping Task

Abstract Objective There remains a need for a non-invasive and cost-effective screening measure that could be administered prior to the provision of a lumbar puncture or positron emission tomography scan for the detection of preclinical Alzheimer disease (AD). Previous findings suggest that a hippocampally-based spatial navigation task may be effective for screening individuals for the preclinical AD continuum (i.e., low cerebrospinal fluid (CSF) Aβ42). Unfortunately, this task took 1.5–2 hours to administer, which would be time-prohibitive in a clinical setting. Therefore, the goal of this study was to compare psychometric properties of six spatial navigation-related tasks in order to take the next steps in developing a clinically appropriate screening measure. Methods Psychometric properties (i.e., reliability, diagnostic accuracy, validity) of a modified version of the cognitive mapping task, two binding tasks, a visual perspective taking task, and self- and informant report versions of a questionnaire were examined in a sample of 91 clinically normal (CN) individuals. CSF Aβ42 and ptau181 were available for 30 individuals. Results The learning phase of the cognitive mapping task and the self-report questionnaire were sensitive to identifying individuals in the preclinical AD continuum (93% and 87% sensitivity, 60% and 67% specificity, respectively). These two measures also demonstrated good test-retest stability (intraclass correlation coefficients = .719 and .838, respectively) and internal consistency (Cronbach’s αs = .825 and .965, respectively). Conclusions These findings suggest that a self-report questionnaire and aspects of a cognitive mapping task may be particularly appropriate for development as screening tools for identifying individuals in the preclinical AD continuum.

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NEUROIMAGING BIOMARKERS OF THE A/T/N CLASSIFICATION SYSTEM PREDICT CROSS-SECTIONAL AND LONGITUDINAL CHANGE IN PRECLINICAL AND EARLY ALZHEIMER DISEASE

Alzheimer s & Dementia ◽

10.1016/j.jalz.2017.07.332 ◽

2017 ◽

Vol 13 (7) ◽

pp. P911

Author(s):

Andrew J. Aschenbrenner ◽

Jason Hassenstab ◽

Brian A. Gordon ◽

Tammie L.S. Benzinger ◽

John C. Morris

Keyword(s):

Alzheimer Disease ◽

Classification System ◽

Longitudinal Change ◽

Cross Sectional ◽

N Classification ◽

Neuroimaging Biomarkers

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Spatial navigation deficits — overlooked cognitive marker for preclinical Alzheimer disease?

Nature Reviews Neurology ◽

10.1038/s41582-018-0031-x ◽

2018 ◽

Vol 14 (8) ◽

pp. 496-506 ◽

Cited By ~ 68

Author(s):

Gillian Coughlan ◽

Jan Laczó ◽

Jakub Hort ◽

Anne-Marie Minihane ◽

Michael Hornberger

Keyword(s):

Alzheimer Disease ◽

Spatial Navigation

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Repeated multi-domain, but not single-domain, cognitive training prevents cognitive decline and amyloid pathology found in the APPNL-G-F mouse model of Alzheimer disease

10.1101/2020.08.24.264978 ◽

2020 ◽

Author(s):

Jogender Mehla ◽

Scott H. Deibel ◽

Hadil Karem ◽

Shakhawat Hossain ◽

Sean G. Lacoursiere ◽

...

Keyword(s):

Alzheimer Disease ◽

Cognitive Training ◽

Cognitive Functions ◽

Spatial Navigation ◽

Single Domain ◽

Control Group ◽

Navigation Task ◽

Aged People ◽

Amyloid Load ◽

And Control

AbstractEducation, occupation, and an active lifestyle, comprising enhanced social, physical, and mental components are associated with improved cognitive functions in aged people and may prevent/ or delay the progression of various neurodegenerative diseases including Alzheimer’s disease (AD). To investigate this protective effect, APPNL-G-F/NL-G-F mice at 3 months of age were exposed to repeated, single- or multi-domain cognitive training. Cognitive training was given at the age of 3, 6, 9 & 12 months of age. Single-domain cognitive training was limited to a spatial navigation task. Multi-domain cognitive training consisted of a spatial navigation task, object recognition, and fear conditioning. At the age of 12 months, behavioral tests were completed for cognitive training groups and control group. After completion of behavioral testing, mice were sacrificed, and their brains were assessed for pathology. AppNL-G-F mice given multi-domain cognitive training compared to APPNL-G-F control group showed an improvement in cognitive functions, reductions in amyloid load and microgliosis, and a preservation of cholinergic function. There were mild reductions in microglosis in the brain of APPNL-G-F mice with singledomain cognitive training. These findings provide causal evidence for the potential of certain forms of cognitive training to mitigate the cognitive deficits in Alzheimer disease.

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Structural and Chemical Studies of Pathological Fibers in Human Neurofibrillary Degeneration

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s042482010012031x ◽

1985 ◽

Vol 43 ◽

pp. 726-729

Author(s):

K.S. Kosik ◽

L.K. Duffy ◽

S. Bakalis ◽

C. Abraham ◽

D.J. Selkoe

Keyword(s):

Monoclonal Antibodies ◽

Alzheimer Disease ◽

Human Brain ◽

Neurofibrillary Tangles ◽

Morphological Analysis ◽

High Specificity ◽

Cytoskeletal Proteins ◽

Neuritic Plaque ◽

Protein Chemistry ◽

Chemical Studies

The major structural lesions of the human brain during aging and in Alzheimer disease (AD) are the neurofibrillary tangles (NFT) and the senile (neuritic) plaque. Although these fibrous alterations have been recognized by light microscopists for almost a century, detailed biochemical and morphological analysis of the lesions has been undertaken only recently. Because the intraneuronal deposits in the NFT and the plaque neurites and the extraneuronal amyloid cores of the plaques have a filamentous ultrastructure, the neuronal cytoskeleton has played a prominent role in most pathogenetic hypotheses.The approach of our laboratory toward elucidating the origin of plaques and tangles in AD has been two-fold: the use of analytical protein chemistry to purify and then characterize the pathological fibers comprising the tangles and plaques, and the use of certain monoclonal antibodies to neuronal cytoskeletal proteins that, despite high specificity, cross-react with NFT and thus implicate epitopes of these proteins as constituents of the tangles.

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