An analysis of systems of classifying mild

cognitive impairment in older people

Alexander Collie, Paul Maruff

Objective: Over the past two decades, a number of systems have been developed for the
classification of cognitive and behavioural abnormalities in older people, in order that individuals at high risk of developing neurodegenerative disease, particularly Alzheimers
disease, may be identified well before the disease manifests clinically. This article critically
examines the inclusion and exclusion criteria of a number of such classification systems,
to determine the effect that variations in criterion may have on clinical, behavioural and
neuroimaging outcomes reported from older people with mild cognitive impairment.
Method: Qualitative review of the literature describing systems of classifying mild cognitive
impairment, and outcomes from clinical, behavioural, neuroimaging and genetic studies of
older people with mild cognitive impairment.
Results: The exclusion and inclusion criteria for these classification systems vary
markedly, as do the design of studies upon which the validity of these systems has been
assessed. Minor changes to individual exclusion/inclusion criterion may result in substantial changes to estimates of the prevalence and clinical outcome of mild cognitive impairment, while inadequate experimental design may act to confound the interpretation of
results.
Conclusions: As a result of these factors, accurate and consistent estimates of the
outcome of mild cognitive impairments in otherwise healthy older people are yet to be
obtained. On the basis of this analysis of the literature, optimal criteria via which accurate
classifications of mild cognitive impairment can be made in future are proposed.
Keywords: cognitive impairment, ageing, memory, diagnosis, neuropsychology.
Australian and New Zealand Journal of Pschiatry 2002; 36:133140

Many recent studies report that a small proportion of

older people perform in the abnormal or borderline
range on neuropsychological tests [1,2], and that these
abnormalities occur predominantly in the domain of
episodic memory [3]. While these people do not meet
the clinical criteria for any neurodegenerative disease,
their performance indicates that their cognitive functions

Alexander Collie, Centre for Neuroscience, The University of Melbourne

(Correspondence); Paul Maruff, School of Psychology, Latrobe University
Neuropsychology Laboratory, Mental Health Research Institute of
Victoria, Locked Bag 11, Parkville, Victoria 3052, Australia.
Email: alex@neuro.mhri.edu.au
Received 11 October 2000; revised 24 August 2001; accepted 28 August
2001.

are not normal. Three accounts of the aetiology of such

mild cognitive impairment have been put forward
recently. The first proposes that it represents the early
stages of Alzheimers disease (AD), while the second
proposes that it is a product of normal ageing [4]. The
third, and most likely, account is that mild cognitive
impairment is a heterogeneous disorder with multiple
possible outcomes [35]. These proposals have been
investigated recently through epidemiological, genetic,
cognitive and neuroradiological studies of older people
classified as having mild cognitive impairment. Results
from these studies have been varied, which has added to
the current confusion and contradiction occurring in the
ageing and dementia literature. We argue that the major
cause of this confusion is the inconsistency among the

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CLASSIFYING MILD COGNITIVE IMPAIRMENT

many different systems that are currently used to classify mild cognitive impairment (hereafter referred to as
classification systems).
Identifying older people at high risk for AD is important for both the patient and their carers as it may allow
therapeutic intervention in the very earliest stages of the
disease, which in turn may delay or even prevent the
onset of the disease process. In the worst case it allows
for the planning of patient care. Such identification is
currently hampered by the use of inadequate and inconsistent diagnostic criteria for mild cognitive impairment.
Nine such criteria have been developed, and a number
of other terms have been used to describe cognitive
dysfunction in older individuals. Table 1 describes these
terms and provides an acronym for each. As well as
being an individual classification system, the term mild
cognitive impairment is used increasingly to describe
cognitive dysfunction associated with ageing. Used in
this context, the term mild cognitive impairment implies
that the different classification systems may be uniform
and comparable, however, as discussed below this is not
the case. Because there are so many terms used for this
phenomenon (see Table 2), mild cognitive impairment
will be used in this review to describe the concept of cognitive impairment associated with ageing that is not
clearly dementia. The acronyms listed in Table 2 will be
used when referring to individual classification systems.
In order to determine whether mild cognitive impairment represents the earliest stages of AD, recent studies

Table 1.
Acronym
AACD
AAMI
ACMD
ACMI
ARCD
ARMD
BSF
IMD
IMI
IML
LCD
LLF
MCD
MCI
MD
MND
QD

have followed individuals classified as impaired according to one of the many available criteria over time
(Table 2). Other recent studies have sought to determine
whether impaired older individuals show increased rates
of other risk factors for AD, including the apolipoprotein
E (ApoE) epsilon 4 allele, hippocampal volume reduction, and self-reported memory loss (Table 2). Both
types of investigation hypothesize that cognitively
impaired older individuals are at greater risk of developing AD than non-impaired individuals. Despite many
such studies being conducted recently, there is still disagreement about the clinical significance and outcome
of mild cognitive impairments in older people. In fact,
there is still debate about the population prevalence of
such impairment among older individuals [5]. Potential
reasons for these differences include inconsistent inclusion and exclusion criteria (Table 3), and variation in
study design (e.g. sample size, baseline/follow-up interval), both of which may have considerable effects on
study outcome. This review aims to compare and contrast the inclusion and exclusion criteria of the published
systems for classifying mild cognitive impairment, and
to determine the effects that changes to these criteria
may have on study outcome. The effect that differences
in experimental design may have on conclusions drawn
from recent studies will also be considered. Based on
this analysis of the literature, optimal criteria for the
accurate identification of mild cognitive impairments
are proposed.

Diagnostic and descriptive terminology for mild cognitive impairment in older people
Title
Ageing Associated Cognitive Decline
Age-Associated Memory Impairment
Age Consistent Memory Decline
Age Consistent Memory Impairment
Age-Related Cognitive Decline
Age-Related Memory Decline
Benign Senescent Forgetfulness
Isolated Memory Decline
Isolated Memory Impairment
Isolated Memory Loss
Limited Cognitive Disturbance
Late Life Forgetfulness
Mild Cognitive Disorder
Mild Cognitive Impairment
Minimal Dementia
Mild Neurocognitive Disorder
Questionable Dementia

Reference
Levy [34]
Crook et al. [35]
Crook [24]
Blackford and La Rue [36]
DSM-IV [11]
Blesa et al. [37]
Kral [38]
Small et al. [12]
Berent et al. [39]
Bowen et al. [40]
Gurland et al. [41]
Blackford and La Rue [36]
Reisberg et al. [25]
Petersen et al. [2]
Roth et al. [42]
DSM-IV [11]
Morris et al. [8]

DSM-IV = Diagnostic and Statistical Manual of Mental Disorders Version 4, published by the American Psychiatric Association
(1994).

A. COLLIE, P. MARUFF

Table 2.

135

Results from selected studies of older people classified as impaired according to different systems

Study
Smith et al. [5]
Barker and Jones [22]
Barker et al. [43]
Soininen et al. [44]
Forstl et al. [29]
Laakso et al. [45]
Krasuski et al. [46]
Jack et al. [47]
Tierney et al. [48]
Bowen et al. [40]
Berent et al. [39]
Petersen et al. [2]
Forstl et al. [29]
Blesa et al. [37]
Bartres-Faz et al. [49]
Hanninen et al. [50]
Fowler et al. [28]
Petersen et al. [2]

System of
Classification
AAMI
AAMI
AAMI
AAMI
AAMI
AAMI
MCI
MCI
N/S
IML
IMI
MCI
AAMI
ARMD
AAMI
AAMI
QD
MCI

Outcome
measure
Prevalence
Prevalence
Prevalence
Brain volume
Brain volume
Brain volume
Brain volume
Brain volume
Clinical outcome
Clinical outcome
Clinical outcome
Clinical outcome
ApoE genotype
ApoE genotype
ApoE genotype
Cognitive function
Cognitive function
Cognitive function

Result
796% depending on memory test used
1558% depending upon criteria
5.815.8% depending on individual criteria
Normal hippocampal volume; hippocampal asymmetry
hippocampal volume
Normal amygdala volume
entorhinal, hippocampal, amygdale volume
hippicampal volume
24% develop AD 2 years after baseline
48% develop AD 31 months after baseline
50% develop AD 3 years after baseline; 15% pseudodementia
48% develop AD 2 years after baseline
58% carry e4 allele;
56% carry e4 allele; 37% e3/3 homozygous; 4% carry e2 allele
18% carry e4 allele; 64% e3/3 homozygous; 18% carry e2 allele
executive function performance
43% display episodic memory function over 12 month period
episodic memory performance

AAMI = Age-Associated Memory Impairment; MCI = Mild Cognitive Impairment; ARCD = Age-Related Cognitive Decline;
IML = Isolated Memory Loss; IMI = Isolated Memory Impairment; QD = Questionable Dementia; = decreased; AD = Alzheimers
disease; ApoE = Apolipoprotein; N/S = system of classification system not specified. Results from studies of older people classified
as having cognitive impairment can vary substantially according to the criteria used to classify impairment. This is true for a number
of different outcome variables, including estimated prevalence of impairment, brain volume measured with Magnetic Resonance
Imaging, apolipoprotein E genotype, clinical outcome (the number of people subsequently meeting criteria for AD), and
performance on tests of cognitive function.

Inclusion and exclusion criteria

Memory impairment
All published classification systems propose as an
inclusion criterion evidence of a memory deficit (Table 3).
This arises from repeated findings that memory is the
first cognitive domain affected by the AD process [2,3,6],
and is also affected by the normal ageing process [7].
However, the classification systems differ as to whether
the memory impairment needs to be identified objectively. For example, the Age-Associated Memory Impairment (AAMI) and Mild Cognitive Impairment (MCI)
criteria require that memory test performance be abnormal relative to a control group, whereas the Age-Related
Cognitive Decline (ARCD) criterion requires only a subjective report of problems recalling names and events. Of
those classification systems that require objective evidence of a memory deficit, there are differences between
the composition of the group against which memory test
performance is compared. For example, the comparison
group specified by the AAMI criterion is normal young
adults, whereas the MCI criterion requires an ageappropriate control group. Healthy young people generally have superior memory test performance than healthy

older people [7], and it is therefore likely that a greater

proportion of older individuals will be classified as
impaired when the AAMI criterion is employed. The
composition of groups of impaired subjects classified
according to AAMI and MCI criteria are also likely to be
different, and their relationships to outcome measures
(e.g. prevalence, progression to AD) not comparable [4].
Other cognitive impairment
Some classification systems propose that memory
impairment be accompanied by deficits in other cognitive domains, although this is not required universally
(Table 3). For example, an individual can be classified as
having Questionable Dementia (QD) when mild impairments are evident in a number of cognitive domains. In
contrast, the criteria for AAMI specifies that cognitive
processes other than memory remain unaffected. Deficits
in cognitive domains other than memory occur predominantly in more advanced stages of AD [8] or in other
neurodegenerative diseases (e.g. vascular dementia [9]),
whereas the earliest stages of AD are characterized by an
isolated memory impairment [3,10]. Therefore, classification systems which require impairment in multiple
cognitive domains are likely to identify individuals in

136

CLASSIFYING MILD COGNITIVE IMPAIRMENT

Table 3.

System of
Classification
Age Associated
Memory
Impairment
Age Related
Cognitive
Decline

Components of systems of classifying cognitive impairment in older people

Memory
Impairment
Yes
Objective

Other
cognitive
impairment
No

Cognitive
decline
Yes
Subjective

Subjective
memory Recommended
loss
cognitive tests
Yes
Yes

Associated
Neurological
disturbance
No

Associated
mood
disturbance
No

Impaired
daily
living
N/S

Yes
Subjective

N/S

N/S

N/S

No

N/S

N/S

N/S

Benign Senescent
Yes
Forgetfulness Subjective

No

No

No

No

N/S

N/S

N/S

Yes*
Objective

Yes*
Objective

Yes
Objective

N/S

No

N/S

N/S

Yes*

Mild Neurocognitive Yes

Disorder
Objective

Yes
Objective

Yes
Objective

No

No

Yes

N/S

Yes

Mild Cognitive
Yes
Decline (GDS 3) Objective

N/S

N/S

Yes

Yes

N/S

Yes

Yes

Mild Cognitive
Impairment

Yes
Objective

No

N/S

No

No

No

No

No

Limited Cognitive
Yes
Disturbance
Objective

No

Yes
Subjective

Yes

No

N/S

N/S

No

Yes
Objective

No

No

Yes

N/S

N/S

Yes

Questionable
Dementia
(CDR 0.5)

Minimal Dementia

Yes
Objective

Note: N/S = Not specified; Yes = required to meet criteria; No = not required to meet criteria; Objective = objectively identified;
Subjective = subjectively identified. *A Clinical Dementia Rating (CDR) of 0.5 may be reached in a number of ways, and memory
impairment may not necessarily be accompanied by deficits in other cognitive domains for CDR 0.5 to be obtained. Similarly, a
CDR of 0.5 may be reached in the absence of memory impairment, provided that impairment is observed in a number of other
domains of function.

whom the AD process is already advanced. Despite this,

it is important to obtain an overall picture of the individuals cognitive function prior to classification according
to any system.
Cognitive decline
An issue yet to be addressed adequately is whether
people with mild cognitive impairment progress to develop
clinically identifiable dementia, or remain impaired without displaying evidence of deteriorating cognitive function [10]. Diagnostic criteria for probable AD requires
objective evidence of cognitive decline [11], however,
many classification systems for mild cognitive impairment fail to specify whether decline should be evident
(Table 3). These varied criteria reflect the different theoretical basis of the individual classification systems.
While some emphasize that mild cognitive impairments
represent early AD, others propose that they are benign
and unrelated to any disease process. This means that the
same mildly impaired individual could be rated as either

normal or dementing depending on which classification

system is employed.
The results of a recent functional neuroimaging study
may shed some light on this issue. Small and colleagues
[12] used functional Magnetic Resonance Imaging
(fMRI) to reveal two separate patterns of hippocampal
dysfunction during facial encoding among 12 people
classified as having Isolated Memory Decline (IMD).
The first pattern was observed in four IMD subjects,
involved all hippocampal regions (entorhinal cortex, hippocampus proper and subiculum), and closely resembled
that observed in four patients with clinically recognizable AD. The second pattern of dysfunction was observed
in eight IMD subjects and was restricted to the subiculum. Recent postmortem findings suggest that selective
subicular damage may occur as a result of normal ageing
[13,14]. These results suggest the existence of two subgroups within the IMD group; one in the early or preclinical stages of AD, and another with memory decline
associated with normal ageing. An ideal system of classifying mild cognitive impairment must therefore be able

A. COLLIE, P. MARUFF

to differentiate impairment associated with ageing and

impairment associated with neurodegenerative processes.
Self-reported cognitive impairment
The classification systems also differ as to whether the
individual need have insight into his/her cognitive impairment (Table 3). There have been conflicting reports
regarding the extent to which subjective complaints of
cognitive loss are predictive of impairment and the future
development of AD [1519]. While some reports indicate that subjective complaints are related to objectively
identifiable cognitive impairment [17], other recent findings have challenged this view [19]. Other recent work
has suggested that self-reported cognitive impairment
may be more closely related to the presence of depressive symptomatology than to objective cognitive impairment [18]. Until a consensus is reached regarding the
value of subjective cognitive function in predicting cognitive dysfunction, it seems specious to include it as an
inclusion criteria for mild cognitive impairment.
Recommended neuropsychological tests
The psychometric properties of individual neuropsychological tests can vary widely, and an individual may
be rated as impaired on one test but normal on another
depending on the sensitivity of the test to the cognitive
domain under study. For example, an older individual
with a mild memory impairment may be rated as normal
on a cognitive screening measure such as the MiniMental State Examination, but impaired on an alternative and more psychometrically reliable and sensitive
test of memory function [10]. Therefore, another important distinction between these classification systems is
the extent to which they emphasize the use of specific
neuropsychological measures for identifying cognitive
abnormalities. This is perhaps best demonstrated by
analysis of estimates of prevalence for the more common
classification systems, which vary widely according to
the neuropsychological test used to rate cognition. For
example, Smith et al. [20] reported that the proportion of
a normal older cohort meeting objective criteria for
AAMI varied between 7% and 96% depending on the
neuropsychological test used.
An important issue appropriate to discuss here is that
of circularity. That is, mild cognitive impairment is often
diagnosed with the same or similar neuropsychological
measures that are then used to characterize cognitive
function in individuals with the disorder (for review
see [3,4]). This situation has arisen as a convenience,
because in the absence of behavioural and cognitive investigation of individuals with mild cognitive impairment,

137

the utility of a classification system would take years

(and perhaps decades) to establish were the gold standard outcome of conversion to probable AD required.
Ideally, diagnostic instruments should be independent of
techniques used to measure outcome in individuals with
mild cognitive impairment [2], which raises the question
of whether neuropsychological tests are appropriate
outcome measures. A resolution to this issue is important
for the planning of future studies and the interpretation
of current studies.
Activities of daily living
Another inconsistency between the classification
systems is that some exclude older people with impaired
activities of daily living (ADL) while others do not.
Impairments in everyday activities are not often observed
until well into the AD process, and it could be argued
that such impairment is related to the severity of the cognitive deficit experienced by the individuals. Therefore,
classification systems that require impairment in ADL
are likely to identify individuals with more severe cognitive deficits than those that do not. Alternatively, such
systems may identify individuals with neurodegenerative
diseases other than AD, where executive function and
physical disorders may cause impaired ADL [9].
Other exclusion criteria
The remaining exclusion criteria are relatively consistent among the classification systems. For example, most
specify the exclusion of individuals with a history of
medical and/or psychiatric illness that could account for
the observed cognitive impairment (Table 3). Most also
require that a classification of impairment be made only
when other possible aetiologies have been ruled out.
However, there are exceptions to this rule. For instance,
classification of Mild Neurocogntive Disorder (MND) is
made only when it can be attributed to the onset of a
medical condition. The specificity of exclusion criteria
varies widely between the classification systems, and
this may have led to the poor predictive ability of some
classification systems. One potential reason that only
approximately 50% of all older people with mild cognitive impairments progress to develop AD may be the
failure to exclude individuals with other causes of mild
impairment unrelated to degenerative processes.
Experimental design
Inconsistent and/or inadequate experimental design
may also have contributed to the variable outcomes
reported from studies of mildly impaired older individuals.

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CLASSIFYING MILD COGNITIVE IMPAIRMENT

For example, in many studies, the proportion of individuals meeting criteria for cognitive impairment is determined from within a small sample (often N < 100). The
increased variability in test scores associated with small
sample sizes means that the degree to which that estimate is an accurate representation of the expression of
cognitive impairment in the population is questionable.
Small sample sizes may also operate to increase the variability in the reported rates of progression to AD in these
studies. The specificity of inclusion and exclusion criteria may also affect reported outcomes. For example, estimates of prevalence for the more strict and explicit
classification systems are generally found to be lower
than for the less strict and poorly defined systems [21].
A recent study by Barker and Jones [22] found that
18.5% of people aged between 50 and 94 years met the
criterion for AAMI described by Crook et al. [23]. A
modified AAMI criterion has also been described, in
which the memory test cut-scores below which performance is said to be impaired were relaxed [24]. When
this modified criterion was applied to the same cohort,
estimated prevalence for people aged between 50 and
94 years was recorded at 25.5%, an increase of 40% on
the previous estimate. The rigor of the exclusion and
inclusion criteria adopted may also affect the observed
rate of progression to AD among these studies, which
have range from five per cent [25] to 69% [26]. Investigations which classify subjects as impaired according to
more strict and well-defined criteria observe higher rates
of conversion to AD than investigations which utilize less
strict and poorly defined classification systems [21,27].
The amount of time between the classification of mild
cognitive impairment and the follow-up assessment at
which clinical outcome is determined may also affect
these estimates. Some studies report outcome five years
after initial classification [2], while others have left as
little as 2 years between classification and follow-up
[28,29]. There is evidence to suggest that the biochemical and neuropsychological changes that precede AD can
be detected up to 20 years before the disease manifests
clinically [3032]. An accurate determination of the rate
of conversion to AD would therefore require longer
periods of observation than have been reported recently.
Summary and conclusions
While all available classification systems for mild cognitive impairment require that the individual display evidence of a memory deficit, other inclusion and exclusion
criteria are much less uniform (Table 3). These inconsistencies have led to discrepant reports regarding the
prevalence, clinical outcome and genetic correlates of
mild cognitive impairment (Table 2). The ultimate aim

of identifying older people with cognitive impairment is

to allow intervention into the preclinical stages of the
neurodegenerative process. However, before the utility
of any such intervention can be determined, precise
estimates of the outcome of such impairment need to
be obtained. The acquisition of these estimates in turn
requires the development and implementation of an accurate classification system for mild cognitive impairment.
Given the considerable differences between the inclusion and exclusion criteria of published classification
systems, there is surprising consensus regarding the cognitive, genetic and cortical correlates of mild cognitive
impairment. Episodic memory impairment, hippocampal
atrophy, and the ApoE e4 allele are all consistently
shown to be associated with cognitive impairment in
older people (Table 2). Although there is substantial variability, the rate of expression of these outcome measures
in older people with mild cognitive impairment is broadly
similar to that observed in patients with clinically diagnosed AD. Other consistent results become evident upon
analysis of the literature. For example, criteria that require
the individual to display moderate deficits report a higher
rate of progression to AD, and a lower estimated rate of
prevalence, than classification systems that require only
mild impairment [21]. A large proportion of older individuals with mild cognitive impairment do not progress
to develop clinically recognizable AD, regardless of
the severity of their deficit [3]. There are two potential
reasons for this common finding. First, the period of time
between classification of impairment and determination
of clinical outcome in many studies may not have been
sufficient for all incipient cases of AD to be expressed
clinically. Second, the systems for classifying cognitive
impairment may not be specific to the preclinical stages
of AD.
Conclusions regarding the optimal criteria for identifying older individuals at high risk for AD can be drawn
from analysis of studies that have employed the existing
systems of classification. First, it seems evident that at
least a moderate episodic memory impairment should
be requisite, and that this memory impairment need
not occur concurrently with deficits in other cognitive
domains. Second, the determination of impairment should
be made against the performance of an age-appropriate
group of normal controls. Third, objective evidence of
cognitive decline from a baseline (or previous) level
of performance should be obtained prior to classification
of impairment. Fourth, the neuropsychological measures on which such comparisons are made should have
sufficient sensitivity to allow the identification of subtle
changes in cognitive function. Fifth, individuals exhibiting depressive and anxiety symptomatology should be
assessed more thoroughly and excluded if the observed

A. COLLIE, P. MARUFF

impairment is thought to be a consequence of that symptomatology. This final criterion should be exercised with
caution, given that AD and depression often co-occur
early in the course of AD [33].
Analysis of the literature also suggests that a number
of methodological and conceptual issues must be
addressed before accurate estimates of the prevalence
and clinical outcome of mild cognitive impairments may
be gained. Methodological issues include that the period
of time between identification of cognitive impairment
and determination of clinical outcome must appropriately reflect the expected length of time between the
onset of the AD process and the clinical diagnosis of the
disease. Also, sample sizes should be large enough that
such findings may be generalized to the population.
Conceptually, we propose that before the value of selfreported cognitive impairment in predicting clinical outcome is determined, subjective ratings should not be
considered as inclusion criteria for mild cognitive
impairment.
References
1. Albert MS. Cognitive and neurobiologic markers of early
Alzheimers disease. Proceedings of the National Academy of
Science 1996; 93:1354713551.
2. Petersen RC, Smith GE, Waring SC et al. Mild cognitive
impairment: clinical characterization and outcome. Archives of
Neurology 1999; 56:303308.
3. Collie A, Maruff P. The neuropsychology of preclinical
Alzheimers disease and mild cognitive impairment.
Neuroscience and Biobehavioural Reviews 2000; 24:365374.
4. Ritchie K, Touchon J. Mild cognitive impairment: conceptual
basis and current nosological status. Lancet 2000;
355:225228.
5. Smith GE, Ivnik RJ, Petersen RC et al. Age-associated memory
impairment diagnosis: problems of reliability and concerns for
terminology. Psychology and Ageing 1991; 6:551558.
6. Petersen RC, Smith GE, Ivnik RJ et al. Memory function in very
early Alzheimers disease. Neurology 1994; 44:867871.
7. Grady CL, Craik FIM. Changes in memory processing with age.
Current Opinion in Neurobiology 2000; 10:224231.
8. Morris JC, Edland SD, Clark C et al. The consortium to
establish a registry for Alzheimers disease (CERAD). Part IV.
Rates of cognitive change in the longitudinal assessment of
probable Alzheimers disease. Neurology 1993; 43:24572465.
9. Looi JCL, Sachdev PS. Differentiation of vascular dementia
from AD on neuropsychological tests. Neurology 1999;
55:670678.
10. Collie A, Maruff P, Shafiq-Antonacci R, Hallup M, Smith M,
Schofield PR, Masters CL, Currie J. Memory decline in healthy
older people: implications for identifying mild cognitive
impairment. Neurology 2001; 56:15331538.
11. American Psychiatric Association. Diagnostic and statistical
manual of mental disorders, 4th edn. Washington DC:
American Psychiatric Association, 1994.
12. Small SA, Perera GM, DeLaPaz R et al. Differential regional
dysfunction of the hippocampal formation among elderly with
memory decline and Alzheimers disease. Annals of Neurology
1999; 45:466472.

139

13. West MJ. Regionally specific loss of neurons in the ageing

human hippocampus. Neurobiology of Ageing 1993;
14:287293.
14. Simic G, Kostovic I, Winblad B, Bogdanovic N. Volume and
number of neurons of the human hippocampal formation in
normal ageing and Alzheimers disease. Journal of Comparative
Neurology 1997; 379:482494.
15. Jorm AF, Christensen H, Korten AE et al. Do cognitive
complaints either predict future decline or reflect past decline? A
longitudinal study of an elderly community sample.
Psychological Medicine 1997; 27:9198.
16. OBrien JT, Beats B, Hill K et al. Do subjective memory
complaints precede dementia? A three year follow up of patients
with supposed beign senescent forgetfulness. International
Journal of Geriatric Psychiatry 1992; 7:481486.
17. Schmand B, Jonker C, Hooijer C, Lindeboom J. Subjective
memory complaints may announce dementia. Neurology 1996;
46:121125.
18. Schmand B, Jonker C, Geerlings MI, Lindeboom J. Subjective
memory complaints in the elderly: depressive symptoms and
future dementia. British Journal of Psychiatry 1997;
171:373376.
19. Small GW, LaRue A, Komo S et al. Predictors of cognitive
change in middle aged and older adults with memory loss.
American Journal of Psychiatry 1995; 52:17571763.
20. Smith GE, Petersen RC, Parisi JE et al. Definition, course and
outcome of mild cognitive impairment. Ageing,
Neuropsychology and Cognition 1996; 3:141147.
21. Almkvist O, Basun H, Backman L et al. Mild cognitive
impairment: an early stage of Alzheimers disease? Journal of
Neural Transmission 1998; Supp 54:2129.
22. Barker A, Jones R. Age-associated memory impairment:
diagnostic and treatment issues. International Journal of
Geriatric Psychiatry 1993; 8:305310.
23. Crook TH. Diagnosis and treatment of normal and pathologic
memory impairment in later life. Seminars in Neurology 1989;
9:2030.
24. Crook TH. Diagnosis and treatment of memory loss in older
patients who are not demented. In: Levy R, Howard R, Burns A,
eds. Treatment and care in old age psychiatry. London:
Wrightson Biomedical, 1993; 95111.
25. Reisberg B, Ferris SH, de Leon MJ, Crook T. The global
deterioration scale for assessment of primary degenerative
dementia. American Journal of Psychiatry 1982;
139:11361139.
26. Rubin EH, Morris JC, Grant EA, Vendegna T. Very mild senile
dementia of the Alzheimer type: clinical assessment. Archives of
Neurology 1989; 46:379382.
27. Morris JC, Storandt M, Miller JP et al. Mild cognitive
impairment represents early stage Alzheimers disease. Archives
of Neurology 2001; 58:397405.
28. Fowler KS, Saling MM, Conway EL et al. Computerized
neuropsychological tests in the early detection of dementia:
prospective findings. Journal of the International
Neuropsychological Society 1997; 3:139146.
29. Forstl H, Hentschel F, Geiger-Kabisch C et al. Age-associated
memory impairment and early Alzheimers disease. Drug
Research 1995; 45:394397.
30. Grady CL, Haxby JV, Horowitz M et al. Longitudinal study of
the early neuropsychological and cerebral metabolic changes in
dementia of the Alzheimer type. Journal of Clinical and
Experimental Neuropsychology 1988; 10:576596.
31. Gray J. Studying the rate of decline in Alzheimers disease:
implications for therapeutic trials. In Racagni G, Brunello N,
Langer SZ, eds. Recent advances in the treatment of
neurodegenerative disorders and cognitive dysfunction. Basel:
Karger, 1994; 187190.

140

CLASSIFYING MILD COGNITIVE IMPAIRMENT

32. Elias MF, Beiser A, Wolf PA et al. The preclinical phase of

Alzheimers disease: a 22 year prospective study of the
Framingham cohort. Archives of Neurology 2000; 57:808813.
33. Jorm AF. Is depression a risk factor for dementia or cognitive
decline: a review. Gerontology 2000; 46:219227.
34. Levy R. Ageing-associated cognitive decline. International
Psychogeriatrics 1994; 6:6368.
35. Crook T, Bartus RT, Ferris SH et al. Age-associated memory
impairment: proposed diagnostic criteria and measures of
clinical change Report of a National Institute of Mental Health
Work Group. Development Neuropsychology 1986; 2:261276.
36. Blackford RC, La Rue A. Criteria for diagnosing age-associated
memory impairment: proposed improvements from the field.
Developmental Neuropsychology 1989; 5:295306.
37. Blesa R, Adroer R, Santacruz P et al. High apolipoprotein e
epsilon 4 allele frequency in age-related memory decline. Annals
of Neurology 1996; 39:548551.
38. Kral VA. Senescent forgetfulness, benign and malignant. Journal
of the Canadian Medical Association 1962; 86:257260.
39. Berent S, Giordani B, Foster N et al. Neuropsychological
function and cerebral glucose utilization in isolated memory
impairment and Alzheimers disease. Journal of Psychiatric
Research 1999; 33:716.
40. Bowen J, Teri L, Kukull W et al. Progression to dementia in
patients with isolated memory loss. Lancet 1997;
349:763765.
41. Gurland BJ, Copeland JR, Kuriansky J et al. The mind and mood
of ageing. Mental health problems of community elderly in New
York and London. Beckenham: Croom Helm, 1982.
42. Roth M, Tym E, Mountjoy CQ et al. A standardised instrument
for the diagnosis of mental disorder in the elderly with special

43.

44.

45.

46.

47.

48.

49.

50.

reference to the early detection of dementia. British Journal of

Psychiatry 1986; 149:698709.
Barker A, Jones R, Jennison C. A prevalence study of
age-associated memory impairment. British Journal of
Psychiatry 1995; 167:642648.
Sioninen H, Partanen K, Pitkanen A et al. Volumetric MRI
analysis of the amygdale and the hippocampus in subjects with
age-associated memory impairment: correlation to visual and
verbal memory. Neurology 1994; 44:16601668.
Laakso MP, Soininen H, Partanen K et al. Volumes of
hippocampus, amygdala and frontal lobes in the MRI-based
diagnosis of early Alzheimers disease: correlation with memory
functions. Journal of Neural Transmission: Parkinsons Disease
& Dementia Section 1995; 9:7386.
Krasuski JS, Alexander GE, Horwitz B et al. Volumes of medial
temporal lobe structures in patients with Alzheimers disease and
mild cognitive impairment (and in healthy controls). Biological
Psychiatry 1998; 43:6068.
Jack CR, Petersen RC, Xu Y et al. Prediction of AD with
MRI-based hippocampal volume in mild cognitive impairment.
Neurology 1999; 52:13971403.
Tierney MC, Szalai JP, Snow WG et al. Prediction of probable
Alzheimers disease in memory-impaired patients: a prospective
longitudinal study. Neurology 1996; 46:661665.
Bartres-Faz D, Junque C, Lopez A et al. ApoE influences
declarative and procedural learning in age-associated memory
impairment. NeuroReport 1999; 10:29232927.
Hanninen T, Hallikainen M, Koivisto K et al. Decline of frontal
lobe functions in subjects with age-associated memory
impairment. Neurology 1997; 48:148153.