Predictors of Alzheimer type dementia in subjects with mild cognitive impairments

190 Pages·2000·1.28 MB·English

Predictors of Alzheimer type dementia in
subjects with mild cognitive impairments
Neuropsych Publishers
' P.J. Visser, Maastricht 2000 (chapters 0,1, 3, 6, 8, 9, appendices A, B.1, B.2, B.3)
Predictors of Alzheimer type dementia in subjects with mild cognitive impairments/ Pieter Jelle Visser. -
Maastricht: Neuropsych Publishers Maastricht. - Ill.
Thesis Maastricht University. - With ref. - With summary in Dutch.
ISBN 90-75579-11-X
NUGI 742
Production: Datawyse | University Press Maastricht
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Predictors of Alzheimer type dementia in subjects with
mild cognitive impairments
PROEFSCHRIFT
ter verkrijging van de graad van doctor aan
de Universiteit Maastricht,
op gezag van de Rector Magnificus, Prof. Dr. A.C. Nieuwenhuijzen Kruseman,
volgens het besluit van het College van Decanen,
in het openbaar te verdedigen op
woensdag 20 september 2000 om 14.00 uur
door
PIETER JELLE VISSER
geboren op 18 september 1968 te Amersfoort
Promotor
Prof. Dr. J. Jolles
Co-promotor
Dr. F.R.J. Verhey
Beoordelingscommissie
Prof. dr. H.M.W. Steinbusch (Voorzitter)
Prof. Dr. T.J. Heeren (Universiteit van Utrecht)
Prof. Dr. M.H.J. Maes
Dr. Ph. Scheltens (Vrije Universiteit Amsterdam)
Prof. Dr. J. Troost
The studies presented in this thesis were performed at the Department of Psychiatry and
Neuropsychology, Institute of Brain and Behavior, University of Maastricht, The Netherlands.
The author gratefully acknowlegdes the colloboration with the University Department of Neurology,
Vrije Universiteit, Amsterdam, The Netherlands (Dr. Ph. Scheltens), the Institute for Research in
Extramural Medicine, Vrije Universiteit, Amsterdam, The Netherlands (Dr. C Jonker, Dr. B. Schmand,
Dr. L. Launer), the Vincent van Gogh Institute for Mental Health, Venray, The Netherlands (Prof. Dr.
W.M.A. Verhoeven, Dr. S. Tuinier, Dr. A. Wester), and the Department of Molecular Genetics,
Flanders Interuniversity Institute for Biotechnology (VIB), Laboratory of Neurogenetics, Born-Bunge
Foundation (BBS), University of Antwerp (UIA), Antwerp, Belgium (Prof. Dr. C.L. van Broeckhoven,
Dr. M. Cruts).
The printing of this thesis was financially supported by Alzheimer Nederland, Aventis Pharma B.V., Eli
Lilly Nederland B.V., Internationale Stichting Alzheimer Onderzoek (ISAO), Janssen-Cilag N.V.,
Novartis Pharma B.V., Sigma-Tau Ethifarma B.V., SmithKline Beecham Farma b.v. en UCB Pharma
B.V.
Voor Astrid
Altijd even bukken voordat we bloemen plukken (Toon Hermans)
Table of contents
0. Prologue 9
1. Introduction
1.1 The preclinical stage of Alzheimer(cid:146)s disease 11
1.2 Problems in recognizing the preclinical stage of AD 12
1.3 Terminology 13
1.4 Aim of the study 15
1.5 Set-up of the study 17
2. Course of objective memory impairment in non-demented subjects 19
attending a memory clinic and predictors of outcome
3. Course of minimal dementia and predictors of outcome 31
4. Distinction between preclinical Alzheimer(cid:146)s disease and depression 43
5. Medial temporal lobe atrophy and memory dysfunction as predictors 55
for dementia in subjects with mild cognitive impairment
6. Medial temporal lobe atrophy predicts Alzheimer(cid:146)s disease in subjects 69
with mild cognitive impairments
7. Brain correlates of memory dysfunction in alcoholic Korsakoff(cid:146)s 83
syndrome
8. Characteristics of preclinical Alzheimer(cid:146)s disease 93
9. General Discussion 105
9.1 Characteristics of preclinical AD 105
9.2 Predictors of AD in subjects with mild cognitive impairments 107
- Age and education 111
- Memory impairment, impairments in other cognitive domains, 112
MMSE score, and functional measures
- Apolipoprotein E genotype 116
- Depression 117
- Atrophy of the medial temporal lobe 118
- Conclusion 121
9.3 The Preclinical AD Scale (PAS): a multidisciplinary approach 122
to the diagnosis of preclinical AD
9.4 Methodological considerations 125
9.5 Concluding remarks 132
- Suggestions for future research in preclinical AD 132
- Clinical relevance 133
- Conclusion 134
Summary 135
Samenvatting (Summary in Dutch) 141
Dankwoord 147
List of publications 149
Curriculum vitae 151
Appendix A. Definitions of mild cognitive impairment 153
Appendix B.1 Predicting cognitive outcome using the Preclinical 159
AD Scale (PAS)
Appendix B.2 Construction of the Preclinical AD Scale (PAS) 171
Appendix B.3 Instructions how to score the Preclinical AD Scale (PAS) 173
References 175
Prologue 0
CASE HISTORY
A 68-year old man A. was referred to a memory clinic by his physician because his
wife complained that he forgot a lot of things. She was afraid that her husband was
becoming demented. During the interview at the memory clinic, it appeared that A.
himself had no problems at all. He had retired 5 years earlier and kept himself busy
with many hobbies. He sang in the church choir and worked in the garden, although
he had recently stopped playing bridge (too tiresome). He still went shopping and
cooked every other day. His wife, however, remarked that the dinner did not taste as
good as it used to. She said that he often went into the cellar to fetch something but
came back with something else. He sometimes forgot who had visited him several
days earlier. His wife considered her husband to be more introvert and sometimes a
little sad, but he had also had these phases in the past. She hoped that some diag-
nosis could be made to take away her uncertainty.
The clinician at the memory clinic went through some clinical rating scales
with the following results: the score on the Mini-Mental State examination
(MMSE) was 28 out of 30 (he missed the day of the month and one word on the
delayed recall item); the stage on the Global Deterioration Scale was 3 (mild cog-
nitive impairment); and the score on the Hamilton Depression Rating Scale was 10
(mild depression). The clinician concluded that dementia was not present. He was
uncertain, though, whether the cognitive complaints were the result of normal aging
or depressed mood, or whether they were a very early manifestation of Alzheimer(cid:146)s
disease. He wondered what to do next. Which diagnostic procedures would be helpful
to make a stronger diagnosis?
The clinician decided to refer A. to a radiologist for an MRI scan of the brain
and to a neuropsychologist for a neuropsychological examination. The following
results were obtained. The radiologist reported on the basis of the MRI scan: (cid:145)no
atrophy, no mass lesions(cid:146). The neuropsychologist remarked: (cid:145)A. is a friendly man,
looks somewhat younger than his calendar age. Highly educated (university). He
cooperates well but considers some of the tests as tiresome. His memory problems
can partly be objectified: performance on the delayed recall of a word list is below
the 10th percentile, while immediate recall and learning are good; recall of a story is
unimpaired. The performance on tests assessing mental speed is variable but within
10 CHAPTER 0
normal limits. High performance for the Trail-Making-Task, low performance on the
Memory Scanning Task. Some suspectibility for interference (Stroop Color Word
Test card 3). No language impairments. IQ is 130 (above average). Conclusion:
impairment of delayed recall. This may be an early manifestation of Alzheimer(cid:146)s
disease, but it can also be secondary to the depressed mood. Retest warranted after 1
year.(cid:146)
The clinician made the diagnosis of aging-associated cognitive decline with a
possible contribution of the depressed mood. A. and his wife were reassured that at
present there was no dementia. The cognitive impairments may have been related to
the depressed mood. He made an appointment for over 12 months.
After 12 months the situation at home was stable, although A. had made some
errors in his handling of financial affairs. The MMSE score was 27. The neuro-
psychological examination revealed improvement of the delayed recall, a decline on
some tests of cognitive speed and fluency, and an IQ of 125. No follow-up appoint-
ment was made.
After 36 months the wife of A. made a new appointment. Her husband forgot
almost everything. He had stopped cooking meals and would sit for hours in front of
the television even if there were no programs on it. The neuropsychological exami-
nation revealed deterioration on all cognitive measures. The diagnosis of probable
AD type dementia was made.
Several questions arise from this case history:
- could AD not have been foreseen in this subject?
- which other diagnostic procedures would have improved the diagnosis at the first
visit?
- was it likely that the cognitive impairment in this subject was related to the
depressed mood?
These clinical questions formed the basis for the research described in this book.