Predictors of cognitive decline in memory clinic patients
Author: Andersson, Christin
Date: 2007-06-08
Location: Hörsalen, plan 4, Novum, Hälsovägen 7-9, Karolinska Institutet, Karolinska Universitetssjukhuset, Huddinge
Time: 09.00
Department: Institutionen för neurobiologi, vårdvetenskap och samhälle / Department of Neurobiology, Care Sciences and Society
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Thesis (5.957Mb)
Abstract
Background: The major challenge in memory clinics is to predict
development as well as non-development of dementia among the
heterogeneous group of patients with cognitive complaints. Since the
advent of pharmacological treatment possibilities for patients with
Alzheimer s disease (AD), much research has been focused on predictors
for dementia since initiation of treatment in the preclinical phase may
prevent development of dementia. At present, there are no tests specific
enough to alone predict cognitive progression or stability. There are
also no biochemical markers available to monitor the neurodegenerative
disease process in AD. Thus there is a need for valid and clinically
easy-to-use methods to differentiate patients who are at high risk of
cognitive decline from those who will not progress. Objectives: The
overall aim of this thesis was to examine which clinical methods that can
be used and in what combinations to differentiate between patients at
high and low risk for cognitive decline and dementia. Material & Methods:
The thesis includes four retrospective studies that were performed among
patients admitted to the Memory Clinic at Karolinska University Hospital
in Huddinge. All patients were non-demented at baseline. They were
clinically followed up during approximately 3 years because suspicion of
a progressive cognitive disorder could not be ruled out at baseline.
Study I investigated the efficacy of a number of neuropsychological tests
for prediction of subsequent cognitive decline and conversion to
dementia. Study II investigated the relationship between episodic memory
function, APOE å4 allele status and levels of cerebrospinal fluid (CSF)
biomarkers: total-tau (T-tau), hyperphosphorylated tau (P-tau) and the 42
amino acid form of beta amyloid (Aâ42). Study III investigated the
relationship between longitudinal changes in CSF biomarkers and cognitive
function. Study IV investigated what combination of clinical methods at
baseline that was most predictive of cognitive decline and conversion to
dementia. Results: Rey Auditory Verbal Learning Test (RAVLT) was the most
efficient neuropsychological test for prediction of memory impairment and
dementia. Cutoff levels in baseline RAVLT were defined and could identify
patients at high and low risk for subsequent cognitive decline. Among
moderately memory impaired patients, low CSF Aâ42 values differentiated
those who did decline from those who did not. The relationship between
episodic memory and CSF biomarkers was affected by the APOE å4 allele,
where APOE å4 carriers who declined cognitively had pathological CSF
T-tau, P-tau and Aâ42. Severely memory impaired patients showed
significantly increasing P-tau levels during cognitive decline and
progression to AD while patients with normal or moderately impaired
memory showed unchanging P-tau levels and remained cognitively stable.
CSF T-tau and Aâ42 did not change during follow-up.
Conclusion: RAVLT is a useful test for identifying patients at high and low risk for cognitive decline. Adding CSF Aâ42 values increase the ability to differentiate those who will decline from those who will not, especially among moderately memory impaired patients. The APOE å4 allele may affect the CSF biomarker levels among patients with memory impairment. Increasing P-tau levels during cognitive decline suggest that P-tau may be useful as a longitudinal marker of the early neurodegenerative process in AD.
Key Words: mild cognitive impairment, dementia, episodic memory, Rey Auditory Verbal Learning Test, neuropsychological assessment, cerebrospinal fluid, total tau, hyperphosphorylated tau, beta-amyloid (Aâ42), apolipoprotein E (APOE) genotype
Conclusion: RAVLT is a useful test for identifying patients at high and low risk for cognitive decline. Adding CSF Aâ42 values increase the ability to differentiate those who will decline from those who will not, especially among moderately memory impaired patients. The APOE å4 allele may affect the CSF biomarker levels among patients with memory impairment. Increasing P-tau levels during cognitive decline suggest that P-tau may be useful as a longitudinal marker of the early neurodegenerative process in AD.
Key Words: mild cognitive impairment, dementia, episodic memory, Rey Auditory Verbal Learning Test, neuropsychological assessment, cerebrospinal fluid, total tau, hyperphosphorylated tau, beta-amyloid (Aâ42), apolipoprotein E (APOE) genotype
List of papers:
I. Andersson C, Lindau M, Almkvist O, Engfeldt P, Johansson SE, Eriksdotter Jonhagen M. (2006). "Identifying patients at high and low risk of cognitive decline using Rey Auditory Verbal Learning Test among middle-aged memory clinic outpatients." Dement Geriatr Cogn Disord 21(4): 251-9
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II. Andersson C, Blennow K, Johansson SE, Almkvist O, Engfeldt P, Lindau M, Eriksdotter-Jonhagen M. (2007). "Differential CSF biomarker levels in APOE-epsilon4-positive and -negative patients with memory impairment." Dement Geriatr Cogn Disord 23(2): 87-95
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Andersson C, Blennow K, Almkvist O, Andreasen N, Engfeldt P, Johansson SE, Lindau M, Eriksdotter-Jonhagen M. (2007). "Increasing CSF phospho-tau levels during cognitive decline and progression to dementia." Neurobiol Ageing. [Accepted]
Fulltext (DOI)
Pubmed
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IV. Andersson C, Almkvist O, Blennow K, Engfeldt P, Lindau M, Johansson SE, Eriksdotter-Jonhagen M. (1970). "CSF beta-amyloid1-42 and verbal episodic memory predict cognitive decline and conversion to Alzheimer´s disease among memory clinic patients." (Manuscript)
I. Andersson C, Lindau M, Almkvist O, Engfeldt P, Johansson SE, Eriksdotter Jonhagen M. (2006). "Identifying patients at high and low risk of cognitive decline using Rey Auditory Verbal Learning Test among middle-aged memory clinic outpatients." Dement Geriatr Cogn Disord 21(4): 251-9
Fulltext (DOI)
Pubmed
View record in Web of Science®
II. Andersson C, Blennow K, Johansson SE, Almkvist O, Engfeldt P, Lindau M, Eriksdotter-Jonhagen M. (2007). "Differential CSF biomarker levels in APOE-epsilon4-positive and -negative patients with memory impairment." Dement Geriatr Cogn Disord 23(2): 87-95
Fulltext (DOI)
Pubmed
View record in Web of Science®
III. Andersson C, Blennow K, Almkvist O, Andreasen N, Engfeldt P, Johansson SE, Lindau M, Eriksdotter-Jonhagen M. (2007). "Increasing CSF phospho-tau levels during cognitive decline and progression to dementia." Neurobiol Ageing. [Accepted]
Fulltext (DOI)
Pubmed
View record in Web of Science®
IV. Andersson C, Almkvist O, Blennow K, Engfeldt P, Lindau M, Johansson SE, Eriksdotter-Jonhagen M. (1970). "CSF beta-amyloid1-42 and verbal episodic memory predict cognitive decline and conversion to Alzheimer´s disease among memory clinic patients." (Manuscript)
Issue date: 2007-05-18
Rights:
Publication year: 2007
ISBN: 978-91-7357-232-3
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