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9 results

  • Identifying Sensitive Measures of Cognitive Decline at Different Clinical Stages of Alzheimer’s Disease

  • Roos J. Jutten, Sietske A.M. Sikkes, Rebecca E. Amariglio, Rachel F. Buckley, Michael J. Properzi, Gad A. Marshall, Dorene M. Rentz, Keith A. Johnson, Charlotte E. Teunissen, Bart N.M. Van Berckel, Wiesje M. Van der Flier, Philip Scheltens, Reisa A. Sperling, Kathryn V. Papp, for the Alzheimer Disease Neuroimaging Initiative, National Alzheimer’s Coordinating Center, the Harvard Aging Brain Study, and the Alzheimer Dementia Cohort
  • Journal: Journal of the International Neuropsychological Society / Volume 27 / Issue 5 / May 2021
  • Published online by Cambridge University Press: 13 October 2020, pp. 426-438
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  • Objective:

    Alzheimer’s disease (AD) studies are increasingly targeting earlier (pre)clinical populations, in which the expected degree of observable cognitive decline over a certain time interval is reduced as compared to the dementia stage. Consequently, endpoints to capture early cognitive changes require refinement. We aimed to determine the sensitivity to decline of widely applied neuropsychological tests at different clinical stages of AD as outlined in the National Institute on Aging – Alzheimer’s Association (NIA-AA) research framework.

    Method:

    Amyloid-positive individuals (as determined by positron emission tomography or cerebrospinal fluid) with longitudinal neuropsychological assessments available were included from four well-defined study cohorts and subsequently classified among the NIA-AA stages. For each stage, we investigated the sensitivity to decline of 17 individual neuropsychological tests using linear mixed models.

    Results:

    1103 participants (age = 70.54 ± 8.7, 47% female) were included: n = 120 Stage 1, n = 206 Stage 2, n = 467 Stage 3 and n = 309 Stage 4. Neuropsychological tests were differentially sensitive to decline across stages. For example, Category Fluency captured significant 1-year decline as early as Stage 1 (β = −.58, p < .001). Word List Delayed Recall (β = −.22, p < .05) and Trail Making Test (β = 6.2, p < .05) became sensitive to 1-year decline in Stage 2, whereas the Mini-Mental State Examination did not capture 1-year decline until Stage 3 (β = −1.13, p < .001) and 4 (β = −2.23, p < .001).

    Conclusions:

    We demonstrated that commonly used neuropsychological tests differ in their ability to capture decline depending on clinical stage within the AD continuum (preclinical to dementia). This implies that stage-specific cognitive endpoints are needed to accurately assess disease progression and increase the chance of successful treatment evaluation in AD.

  • Relationship between progression of brain white matter changes and late-life depression: 3-year results from the LADIS study

  • Michael J. Firbank, Andrew Teodorczuk, Wiesje M. Van Der Flier, Alida A. Gouw, Anders Wallin, Timo Erkinjuntti, Domenico Inzitari, Lars-Olof Wahlund, Leonardo Pantoni, Anna Poggesi, Giovanni Pracucci, Peter Langhorne, John T. O'Brien,
  • Journal: The British Journal of Psychiatry / Volume 201 / Issue 1 / July 2012
  • Published online by Cambridge University Press: 02 January 2018, pp. 40-45
  • Print publication: July 2012
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  • Background

    Brain white matter changes (WMC) and depressive symptoms are linked, but the directionality of this association remains unclear.

    Aims

    To investigate the relationship between baseline and incident depression and progression of white matter changes.

    Method

    In a longitudinal multicentre pan-European study (Leukoaraiosis and Disability in the elderly, LADIS), participants aged over 64 underwent baseline magnetic resonance imaging (MRI) and clinical assessments. Repeat scans were obtained at 3 years. Depressive outcomes were assessed in terms of depressive episodes and the Geriatric Depression Scale (GDS). Progression of WMC was measured using the modified Rotterdam Progression scale.

    Results

    Progression of WMC was significantly associated with incident depression during year 3 of the study (P = 0.002) and remained significant after controlling for transition to disability, baseline WMC and baseline history of depression. There was no significant association between progression of WMC and GDS score, and no significant relationship between progression of WMC and history of depression at baseline.

    Conclusions

    Our results support the vascular depression hypothesis and implicate WMC as causal in the pathogenesis of late-life depression.

  • Improving the Accuracy and Precision of Cognitive Testing in Mild Dementia

  • Hans Wouters, Bregje Appels, Wiesje M. van der Flier, Jos van Campen, Martin Klein, Aeilko H. Zwinderman, Ben Schmand, Willem A. van Gool, Philip Scheltens, Robert Lindeboom
  • Journal: Journal of the International Neuropsychological Society / Volume 18 / Issue 2 / March 2012
  • Published online by Cambridge University Press: 30 December 2011, pp. 314-322

  • The CAMCOG, ADAS-cog, and MMSE, designed to grade global cognitive ability in dementia have inadequate precision and accuracy in distinguishing mild dementia from normal ageing. Adding neuropsychological tests to their scale might improve precision and accuracy in mild dementia. We, therefore, pooled neuropsychological test-batteries from two memory clinics (ns = 135 and 186) with CAMCOG data from a population study and 2 memory clinics (n = 829) and ADAS-cog data from 3 randomized controlled trials (n = 713) to estimate a common dimension of global cognitive ability using Rasch analysis. Item difficulties and individuals’ global cognitive ability levels were estimated. Difficulties of 57 items (of 64) could be validly estimated. Neuropsychological tests were more difficult than the CAMCOG, ADAS-cog, and MMSE items. Most neuropsychological tests had difficulties in the ability range of normal ageing to mild dementia. Higher than average ability levels were more precisely measured when neuropsychological tests were added to the MMSE than when these were measured with the MMSE alone. Diagnostic accuracy in mild dementia was consistently better after adding neuropsychological tests to the MMSE. We conclude that extending dementia specific instruments with neuropsychological tests improves measurement precision and accuracy of cognitive impairment in mild dementia. (JINS, 2012, 18, 314–322)

  • Chapter 13 - Cerebral microbleeds and Alzheimer'sdisease

  • from Section 3 - Microbleeds in relation to specific populations, diseases and neurological symptoms
  • Edited by David J. Werring, Institute of Neurology, London
  • Book: Cerebral Microbleeds
  • Published online: 05 July 2011
  • Print publication: 26 May 2011, pp 117-124

  • Summary

    In Alzheimer's disease (AD), cerebral microbleeds (CMBs) play a crucial role in the pathophysiology of the disorder. This chapter reviews the available data that help in considering the meaning of CMBs in clinical terms and the underlying pathology in the context of AD. Evidence on the underlying pathology of CMBs can be sought from neuropathology studies, anatomical distribution in AD and clinical studies on related factors. Most studies on CMBs in AD demonstrated a cortico-subcortical predominance, but with some patients exhibiting CMBs both in deep and cortico-subcortical locations. Cerebral microbleeds are strongly linked to hypertensive vasculopathy. With studies on the relevance of CMBs in AD emerging, CMBs have become a factor of interest in the design of clinical trials, particularly with regard to the new generation of immunization therapies, which have been linked to the development of new CMBs.

  • 5 - Structural neuroimaging

  • from Section 1 - Diagnosis
  • Edited by Lars-Olof Wahlund, Karolinska Institutet, Stockholm, Timo Erkinjuntti, University of Helsinki, Serge Gauthier, McGill University, Montréal
  • Book: Vascular Cognitive Impairment in Clinical Practice
  • Published online: 15 September 2009
  • Print publication: 12 February 2009, pp 58-69

  • Summary

    This chapter describes brain abnormalities that can be observed on magnetic resonance imaging (MRI) in patients with vascular dementia (VaD). It presents an overview of MRI abnormalities indicative of cerebrovascular disease. Computed tomography (CT) is sufficient to rule out causes of cognitive decline other than VaD or neurodegenerative types of dementia. In addition, infarcts can be observed on CT, and small-vessel disease and atrophy are appreciable to some extent. Cerebral autosomal dominant arteriopathy with subcortical infarcts and leukoaraiosis (CADASIL) is a hereditary form of VaD, presenting in young patients in the absence of vascular risk factors. On imaging, diffuse white matter hyperintensities involving the U-fibers are characteristically observed, mainly in the temporal, temporopolar, and frontal regions. Quantitative methods such as diffusion tensor imaging (DTI) and magnetization transfer imaging (MTI) provide valuable new ways to assess the integrity of white matter in more detail.