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As the older adult population increases in the coming decades, the number of persons that develop dementia of the Alzheimer’s type (DAT) will increase accordingly. Though curative treatment for Alzheimer’s disease remains elusive, early detection of cognitive decline allows for initiation of pharmacological treatment to slow disease progression and non-pharmacological approaches to support quality of life and well-being of affected individuals and their care partners. Streamlined approaches that bridge the gap between brief screenings and comprehensive neuropsychological evaluation are needed. The NIH Toolbox Cognition Battery (NIHTB-CB) is a brief, easily administered, computerized cognitive battery that assesses various aspects of both fluid and crystallized cognitive abilities. ARMADA (Advancing Reliable Measurement in Alzheimer’s Disease and Cognitive Aging) is a multi-site study that aims to validate the NIHTB across the spectrum from normal aging to DAT. The current study utilized longitudinal data from ARMADA to determine whether performance on the NIHTB-CB detects cognitive decline in persons with normal cognition (NC), mild cognitive impairment (MCI), and mild DAT over the span of two years. We predicted that scores would decline for the MCI and DAT groups, but not for the NC group.
Participants and Methods:
Participants were 191 participants drawn from the larger ARMADA cohort aged 65-84 (nNC = 118, nMCI = 47, nDAT = 26) that completed the NIHTB-CB at baseline and 12 months. The clinical groups were significantly older than the NC group at baseline (MNC = 72.72, MMCI = 76.63, MDAT = 75.42; p < .001) and the NC and MCI groups had significantly more years of education than the DAT group (MNC = 17.03, MMCI = 16.83, MDAT = 15.54; p = .008).
Results:
Mixed model ANOVAs determined differences in uncorrected NIHTB-CB scores between clinical groups at baseline and 12 months, controlling for age and education. There were significant interactions between time and clinical group for Flanker (p < .001), Pattern Comparison (p < .001), and Picture Vocabulary (p = .001), such that the DAT group demonstrated a more negative slope of change than the NC and MCI groups. For Oral Reading, the MCI group demonstrated a more negative slope of change than the NC and DAT groups (p = .01).
Conclusions:
Differential score trajectories were found for the Flanker task, with a more negative pattern of change in scores in the DAT group compared to the NC and MCI groups. Contrary to expectation, scores decreased for the two crystallized subtests across groups, which may reflect regression to the mean given high baseline scores, especially for Picture Vocabulary; however, these results were also moderated by group with less decline in scores in the NC group, which may indicate involvement of non-crystallized abilities in executing a single word comprehension task. Group differences were subtle, which may in part reflect the relatively short period of follow up. The Flanker task appears to be most sensitive to decline in mild DAT compared to MCI and NC. Results provide preliminary support for the utility of NIHTB-CB in detecting cognitive decline along the cognitive aging to DAT spectrum.
Primary progressive aphasia (PPA) is a dementia syndrome characterized by initial development of progressive language deficits in the absence of impairment in other cognitive domains. It has historically been difficult to assess the presence or nature of true memory deficits in this population due to interference from language disturbance on task performance. The Three Words Three Shapes test (3W3S) is a relatively easy memory task that evaluates both verbal and nonverbal memory within the same modality and assesses different aspects of memory, including incidental encoding, effortful encoding, delayed recall, and recognition. Persons with PPA show a material-specific dissociation in performance on 3W3S; specifically, deficits in incidental encoding and recall are limited to verbal, not nonverbal material, in PPA, with preserved recognition of both types of information. However, it is unknown whether this pattern persists over time as the disease progresses.
Participants and Methods:
Participants were 73 participants enrolled in an observational PPA research study at the Mesulam Center for Cognitive Neurology and Alzheimer’s Disease (Mage = 66.75 years, SD = 6.77; Meducation = 16.11 years, SD = 2.38; 51% female). Participants were subtyped as semantic (n = 15), logopenic (n = 27), or agrammatic PPA (n = 31) based on Gorno-Tempini et al., 2011, using 3W3S and other neuropsychological measures as described previously. Participants were followed at 2-year intervals and tests were administered longitudinally. All participants in the current study had 3W3S scores from at least two research visits collected between September 2012 and September 2022.
Results:
There were no significant baseline group differences on 3W3S performance, except for better incidental encoding in the logopenic than the semantic group for shapes (p = .040) and words (p = .043). We then conducted a mixed measures ANOVAs to determine baseline within-person comparisons between words vs shapes. Within individuals, performance on incidental encoding, effortful encoding, and recognition was worse for words than shapes (ps < .01). There was an interaction between material and group for delayed recall (p < .001) such that there was a significantly larger discrepancy between word and shape recall in the semantic (Mdiff = -9.14) compared to logopenic (Mdiff = -3.07) and agrammatic groups (Mdiff = -2.13). Repeated measures ANOVAs determined changes in scores over time collapsed across PPA subtypes. Incidental encoding (ps = <.01), effortful encoding (ps < .05), and delayed recall (ps < .01) declined for both words and shapes over time. Copy and recognition of words (ps < .05), but not shapes declined over time.
Conclusions:
The current results are consistent with prior findings of relative preservation of memory for nonverbal compared to verbal material in PPA as measured by 3W3S, especially in the semantic subtype. Learning and recall of words and shapes declined over time in all groups, whereas there was selective decline in copy and recognition of words compared to shapes. These results provide evidence of differential patterns of decline in certain aspects of memory over time in PPA and highlight the relative preservation of memory in this language-focused dementia even over time.
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