Insidens MCI 2012

8/13/2019 Insidens MCI 2012

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Mild cognitive impairment: Disparity of incidence andprevalence estimates

Alex Warda,*, H. Michael Arrighib, Shannon Michelsa, Jesse M. Cedarbaumb

aUnited BioSource Corporation, Center for Epidemiology and Database Analytics, Lexington, MA, USAbElan Pharmaceuticals Inc, South San Francisco, CA, USA

Abstract Background: The purpose of conducting this study was to identify areas of concordance and sources

of variation for the published rates of prevalence and incidence associated with various definitions for

mild cognitive impairment (MCI).

Methods: The study used systematic review of studies published in English since 1984. Studies were

identified by searching MEDLINE and EMBASE databases. Population-based observational studies

of incidence or prevalence of MCI and related terms were eligible for inclusion.

Results: A total of 3,705 citations were identified, and 42 were accepted for inclusion; 35 included

data on prevalence and 13 on incidence. The following four terms predominated: age-associated

memory impairment (AAMI); cognitive impairment no dementia (CIND); MCI; and amnestic

MCI (aMCI). Within each term, the operational definition varied. Substantial variation was observed

for both incidence (MCI: 21.571.3; aMCI: 8.525.9 per 1,000 person-years) and prevalence of each

definition of cognitive impairment (AAMI 3.6%38.4%; CIND 5.1%35.9%; MCI 3%42%; aMCI

0.5%31.9%). CIND and MCI showed increasing prevalence among older age groups, whereas age-

specific rates of aMCI were lower and without any apparent age relationship.

Conclusions: Prevalence and incidence estimates associated with MCI vary greatly both between

definitions and within a definitionacross the42 publications. These wide differences pose a significant

challenge to our understanding of the social burden of this disease. Enhancement and standardizationof operational definitions of the subtypes of cognitive impairment could improve estimates of disease

burden and provide a mechanism to assist in the identification of individuals at risk for future

Alzheimers disease and other dementias.

2012 The Alzheimers Association. All rights reserved.

Keywords: Mild cognitive impairment; Amnestic; Epidemiology; Prevalence; Incidence

1. Introduction

Many approaches, diagnostic criteria, and terms have

been proposed and applied to describe mild forms ofcognitive impairment, without dementia, in the elderly

population. Ten years ago, Petersen et al proposed diagnostic

criteria for mild cognitive impairment (MCI) to describe

a transitional state associated with memory impairment

(with normal general cognitive function) that was associated

with an increased risk of progression to Alzheimers disease(AD)[1]. Although MCI is a recognized risk factor for AD,

many individuals revert to normal or do not progress [2,3].

As interest in the pre-dementia phase increased and our

knowledge evolved, heterogeneity in the use of the term

MCI was recognized and additional subclassifications were

also suggestedleading to modifications in the corre-

sponding terminology and criteria[4,5].

Partially because of the changing definitions and research

methods, published estimates of MCI incidence and preva-

lence have been difficult to compare across studies, as the

differences in rates may be because of changes in the

H. Michael Arrighi is currently at JANSSEN Alzheimer Immunother-

apy, South San Francisco, CA, USA. Jesse M. Cedarbaum is currently at

Cytokinetics, South San Francisco, CA, USA.

*Corresponding author: Tel.: 11-781-960 0227; Fax: 11-781-761-

0147.

E-mail address:[email protected]

1552-5260/$ - see front matter 2012 The Alzheimers Association. All rights reserved.doi:10.1016/j.jalz.2011.01.002

Alzheimers & Dementia 8 (2012) 1421
mailto:[email protected]://dx.doi.org/10.1016/j.jalz.2011.01.002http://dx.doi.org/10.1016/j.jalz.2011.01.002http://dx.doi.org/10.1016/j.jalz.2011.01.002http://dx.doi.org/10.1016/j.jalz.2011.01.002mailto:[email protected]


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many different diagnostic criteria applied [2,3]. Thus,

a systematic review of the literature was undertaken to

identify areas of concordance and sources of variation for

the rates of prevalence and incidence associated with

various MCI definitions: cognitive impairment, no

dementia (CIND), age-associated memory impairment

(AAMI), MCI, and amnestic MCI (aMCI).

2. Methods

The literature search was performed using both elec-

tronic and manual components. MEDLINE (via PubMed)

and EMBASE were searched using key words indicative

of MCI and epidemiology, prevalence, or incidence. Each

search strategy was adapted to the idiosyncrasies of each

database using the appropriate index structures (e.g.,

Medical Subject Headings in MEDLINE, and EMTREE

in EMBASE). Case reports, letters, commentaries, edito-

rials, reviews, clinical trials, meta-analyses, practice guide-lines, and in vitro studies were excluded. The search period

was between January 1, 1984 and August 28, 2008, with

limits for English language and humans. In addition to

searching MEDLINE and EMBASE, other strategies

were used to identify recently published articles that might

not yet have been indexed. The PubMed search included

a key word search for the past 6 months, with no limits;

Current Contents database was searched for the past 6

months using similar search terms. A manual check of

the reference lists of all accepted articles and recent

reviews was also performed to supplement the aforemen-

tioned electronic searches.The articles selected for this study met the following

inclusion criteria: population-based observational study, in-

vestigating the incidence or prevalence of MCI (including

prodromal AD, early AD, AAMI, CIND, MCI, and aMCI),

and English language. Cases in which multiple reports of

the same patient population were published (kin studies),

those with the most complete data were used to avoid double

counting.

Data elements of interest were extracted to data forms

developed specifically for use in this review. The data extrac-

tion was performed by 1 investigator and reviewed for agree-

ment (consensus) by a second. One investigator extracted thedata from each study, and a second investigator then inde-

pendently reviewed each study to confirm all data elements

(and blank fields) against the original articles. Data discrep-

ancies were resolved by consensus of the 2 investigators.

The study characteristics, patient characteristics, and key

information from each accepted study were tabulated for

each study. The information retrieved included sampling

method, country, case ascertainment method, diagnostic

criteria applied, the instruments used, and the reported prev-

alence and incidence.

Study characteristics and patient-level data were first

summarized using basic descriptive statistics (simple counts,means, and ranges) organized by type, incidence, or preva-

lence. The letter k denotes the number of studies, and

the letter n denotes the number of subjects.

3. Results

3.1. Search yields

The literature search through MEDLINE (via PubMed),

EMBASE, Current Contents, and manual bibliography

checks yielded 3,705 citations, not including duplicate cita-

tions from the various sources. A total of 42 studies were

eligible for inclusion in this review; 35 primary (parent) stud-

ies for the prevalence estimates[640]and 13 for incidence

[7,10,18,35,36,4047]. Six studies had estimates of

incidence and prevalence [7,10,18,35,36,40]. Reasons for

rejection included nonobservational study, nonpopulation-

based study, and no prevalence or incidence of MCI (or

synonyms thereof).

3.2. Prevalence

A total of 35 studies reporting prevalence were summa-

rized for this review. The key characteristics and details of

included studies by MCI definition and country are

presented in Table 1. The studies were conducted in

Europe (42.9%, k 5 15), North America (31.4%, k 5

11), Asia (17.1%, k 5 6), Australia (5.7%, k 5 2), and

Africa (2.9%, k5 1). The study population ranged from

34 to 10,263 individuals. Typically, the inclusion criteria

ensured that an elderly population was studied, although

the age groups selected for each study varied widely(Table 1).

The terminology for the definition used in the studies re-

porting prevalence was in the following 4 categories: AAMI

(k5 4), CIND (k5 12), MCI (k5 10), and aMCI (k5 14).

The median of the prevalence estimates published in these

studies is as follows: AAMI: 15.6%, CIND: 20.6%, MCI:

26.4%, and aMCI: 4.9%. However, the prevalence varied

over a broad range within each of these 4 definitions:

AAMI: 3.6%38.4%, CIND: 5.1%35.9 %, MCI: 3%

42%, and aMCI: 0.5%31.9%. Many of the studies were

conducted in the United States or Italy, and the estimates

for MCI and CIND were generally lower in Italy. The US es-timates for MCI and CIND prevalence in comparably aged

populations were somewhat similar to four MCI estimates

ranging from 18.8% to 28.3%, and two CIND estimates of

22.2% and 22.8%. The two Italian studies had rates of

7.7% and 3.2%, and the three CIND studies had rates of

5.1%, 10.7%, and 20.6%, with all but one study reporting

lower than US-based prevalence rates.

Most studies selected elderly patients; however, one

applied a markedly lower age limit. Coria et al[12]included

persons aged 40 years, whereas Pioggiosi et al [30]and

Boeve et al[8] enrolled persons aged 90 years. The prev-

alence rates of MCI and CIND are generally observed to in-crease with age (between ages 65 and 85) (Table 2), whereas

A. Ward et al. / Alzheimers & Dementia 8 (2012) 1421 15


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no age-dependent trend was observed in the studies using

definitions of AAMI or aMCI.

3.3. Incidence

A total of 13 studies reporting incidence of MCI were

summarized for this review, and the key characteristics and

details of included studies are presented inTables 3 and 4.

The studies were conducted in North America (46%,

k5 6), Europe (46%, k5 6), and Africa (8%, k5 1). The

study population size ranged from 197 to 2,963 at-risk indi-viduals. The inclusion criteria generally included a minimum

age; the minimum age was set at 60 years for 1 study[45], at

age 65 years in 7 studies[7,18,35,36,42,44,46], age 70 years

in 1 study[43], and age 75 years in 3 studies[10,40,41]. One

study did not specify the age limit[47].

The cumulative incidence estimates are provided inTable

3. Five studies reported cumulative incidence, and the

follow-up period ranged from 2 to 5 years. Although two

5-year studies were publications from the Canadian Study

of Health and Aging, each reported cumulative incidence

from different populations participating in the study (Hsiung

et al [42] and Tuokko et al [46]). The lowest cumulativeincidence was observed for the single study of aMCI [18].

Table 1

Studies reporting estimates of MCI prevalence

Study-level

information

MCI or synonym

definition Location

Years of

study N

Mean age

(range)

Prevalence

% (95% CI)

Koivisto et al, 1995 AAMI Finland 19891992 1049 68.8 (6078) 38.4

Schroder et al, 1998 AAMI Germany NR 202 (6064) 13.5

Pioggiosi et al, 2006 AAMI Italy 19941996 34 (90) 17.6 4.830.5Coria et al, 1993 AAMI Spain 1990 476 (40) 3.6 2.15.7

Low et al, 2004 CIND Australia NR 42 74.4 33.3

Jungwirth et al, 2005 CIND Austria 2000 592 75 23.8 20.427.5

DeRonchi et al, 2007 CIND Italy 19921993 7930 72.6 (61107) 5.1 4.65.6

DiCarlo et al, 2000 CIND Italy 19921993 3425 (6584) 10.7 9.611.7

Dubois and Hebert, 2006 CIND Canada 1991 10,263 (65) 8.7*

Pioggiosi et al, 2006 CIND Italy 19941996 34 (90) 5.9 0.013.8

Prencipe et al, 2003 CIND Italy 1992 968 (65) 20.6

Kumamoto et al, 2000 CIND Japan 19961997 945 72.5 10.8

Baiyewu et al, 2002 CIND Nigeria NR 423 77.7 35.9

Fish et al, 2008 CIND UK 19792004 1209 (6584) 15.6 13.717.8

Plassman et al, 2008 CIND US 20012005 856 (71) 22.2 18.725.7

Unverzagt et al, 2001 CIND US NR 457 (65) 22.9 18.127.7

Huang et al, 2005 MCI China NR 920 (55) 3.0

Artero et al, 2008 MCI France NR 6892 65 42.0

Pioggiosi et al, 2006 MCI Italy 19941996 34 (90) 32.4 16.648.1

Ravaglia et al, 2008 MCI Italy 19992004 937 (65) 7.7 6.19.7

Choi et al, 2008 MCI Korea 20052006 1215 (65) 32.9

Boyle et al, 2006 MCI US NR 786 80.5 (55100) 28.1

Lopez, 2003 MCI US 19911999 3608 (65) 18.8 17.320.4

Manly et al, 2005 MCI US NR 1313 (65) 28.3 25.930.8

Purser et al, 2005 MCI US 19811991 3673 74y 24.7

Solfrizzi et al, 2004 MCI Italy 19921995 4521 73.4 3.2 2.63.7

Kivipelto et al, 2001 aMCI Finland 19721998 1449 74 4.8

Kumar et al, 2005 aMCI Australia 20012002 2551 (6064) 3.7 2.327.5

Low et al, 2004 aMCI Australia NR 42 74.4 9.8

Kim et al, 2007 aMCI Korea 20042006 1215 (60) 31.9

Meguro et al, 2004 aMCI Japan 19982001 1501 (65) 4.9

Manly et al, 2005 aMCI US NR 1313 (65) 5.0 3.86.2Jungwirth et al, 2005 aMCI Austria 2000 592 75 0.5 0.11.5

Busse et al, 2003 aMCI Germany NR 1045 (75) 3.1 2.04.2

Das et al, 2007 aMCI India 20032004 745 66.8 6.0

Fisk et al, 2003 aMCI Canada NR 1790 (65) 1.0 0.71.4

Tognoni et al, 2005 aMCI Italy 2000 1600 74.7 4.9

Boeve et al, 2003 aMCI US 19971999 160 (9099) 12.0

Ganguli et al, 2004 aMCI US 19872001z 1248 74.6 3.2

Verghese et al, 2006 aMCI US 19802001 488 (7585) 10.5

Abbreviations: AAMI, age-associated memory impairment; CIND, cognitive impairment no dementia; MCI, mild cognitive impairment; aMCI, amnestic MCI.

*Derived from gender-stratified data.yMedian age.zEvaluated in waves; biennial evaluation.

A. Ward et al. / Alzheimers & Dementia 8 (2012) 142116


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Eight studies reported incidence rates per person-years

follow-up (Table 4). For people 65 years, the overall inci-

dence rate for MCI ranged from 21.5 to 71.3 per 1,000

person-years. For aMCI, the rates were lower in most of

the studies and ranged from 8.5 to 25.9 per 1,000 person-

years. Three of the studies of aMCI restricted the populationto a minimum of 75 years at baseline, and these rates ranged

between 8.5 and 21.4 per 1,000 person-years[10,40,41].

Five studies reported age-stratified rates (Table 5); 3 of

these selected elderly populations either aged 75 years or

70 years at baseline[10,4143]. Three studies concluded

that the incidence did not increase with age within the age

ranges studied [10,36,43], whereas the other 2 observed

significant increases with age [35,41]. All 5 studies

reported stratified results for the population aged 7579

years and aged 8084 years at baseline. Examining the

rates for the population aged 7584 years, there is

extensive across-study variation in rates, and the confidenceintervals are wide and inconclusive within the studies.

4. Discussion

This review summarizes the published MCI prevalence

and incidence estimates from population-based studies. Sub-

stantial variation was observed for both incidence (MCI:

21.571.3 per 1,000 person-years, aMCI: 8.525.9 per1,000 person-years) and prevalence for each definition of

MCI (AAMI: 3.6%38.4%, CIND: 5.1%35.9%, MCI:

3%42%) and aMCI (0.5%31.9%). The studies of CIND

and MCI consistently showed increasing prevalence with

increasing age between the ages of 65 and 85 years. The

aMCI prevalence was markedly lower in most studies, and

did not show the same trend to increase with age in the stud-

ies reporting age-stratified estimates within the elderly pop-

ulations studied.

Bischkopf et al conducted a review of studies on the

prevalence and incidence of MCI published before 2002

[48]. Although many additional studies were identified forinclusion in the current review, the differences in the specific

Table 2

Age-stratified MCI prevalence

Study-level information

MCI or synonym

definition 5054 5559 6064 6569 7074 7579 8084 8589 90 65

Coria et al, 1993 AAMI 2.1 2.9 9.0 16.6* 7.1

Koivisto et al, 1995 AAMI 45.7 37.6 38.7 33y

Pioggiosi et al, 2006 AAMI 17.6Schroder et al, 1998 AAMI 13.5

DiCarlo et al, 2000 CIND 5.5 8.3 16.4 19.2

Dubois and Hebert, 2006z CIND 2.7 3.7 8.1 12.5 18.7 18.9 8.7

Fish et al, 2008 CIND 9.7 14.3 19.2 35.7

Kumamoto et al, 2000 CIND 6 6.5 12.2 25 21.1

Pioggiosi et al, 2006 CIND 5.9

Plassman et al, 2008 CIND 16x 29.2 39

Prencipe et al, 2003 CIND 20.6

Unverzagt et al, 2001 CIND 19.4 27.2 30.2 22.9

Artero et al, 2008 MCI 42

Choi et al, 2008 MCI 32.9

Lopez et al, 2003 MCI 14.7 22.6 28.9 18.8

Manly et al, 2005 MCI 24{ 32.6** 28.3

Pioggiosi et al, 2006 MCI 32.4

Ravaglia et al, 2008 MCI 5.4 5.6 2.5 12.8 30.1 7.7

Solfrizzi et al, 2004 MCI 5.9 17.2

Boeve et al, 2003 aMCI 12

Busse et al, 2003 aMCI 2.7 3.2 3.9

Das et al, 2007 aMCI 4.96 9.02 3.13 6.15 6.41 6.73

Fisk et al, 2003 aMCI 1.03

Kumar et al, 2005 aMCI 3.7

Manly et al, 2005 aMCI 3.8{ 6.3** 5

Meguro et al, 2004 aMCI 4.9

Tognoni et al, 2005 aMCI 6.3yy 4.1 6.1 2.6 3.4 1.6

Verghese et al, 2006 aMCI 10.5

*Data for 85 to 94.yData for 75 to 78.zDerived from gender-stratified data.xData for 71 to 79.{Data for 65 to 75.

**Data for .75.yyData for 6469.



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operationalization of these criteria varied between studies

because no instruments were specified in the criteria, and

some researchers also described modifying the criteria

[35,43]. Population-based studies have not always included

the criteria of subjective memory complaints; this was consid-

ered reasonable when objective evidence of memory impair-

ment was a component of the case definition. For example,

Solfrizzi et al applied these criteria retroactively to some ofthe patients in the study and did not require subjective mem-

ory impairment or intact Instrumental Activities of Daily Liv-

ing[35]. However, these modifications to the criteria have

been shown to substantially influence the prevalence esti-

mate. A retrospective study by Fisk et al applied the criteria

of subjective memory impairment and intact Instrumental

Activities of Daily Living and reported that this lowered the

estimates by more than half, and then obtained estimates sim-

ilar to those by Solfrizzi et al[17]. Application of modifica-

tions to the case ascertainment criteria, even by experienced

clinicians and researchers, may lead to the selection of

slightly different populations. This may explain the generaltrend observed for similar US estimates for MCI (18.8% to

28.3%) or aMCI (3.2%, 5%, and 10.5%) and differences

either in implementation or the definitions applied by the

Italian researchers, yielding lower estimates (MCI 7.7% or

3.2% and aMCI 4.9%).

The wide variation in the published overall prevalence

estimates may be partially because of differences in the

age distributions of the populations studied. Some studies

derived estimates for populations aged 65, 75, or 90

years, whereas others included much younger age groups

(40 or 55 years). In addition, the specific proportion of

the population in each of the age categories is expected to in-fluence the estimated prevalence. Also, some studies were

based on a limited number of participants, thereby resulting

in unstable age-specific rates.

Few of the incidence studies were conducted with similar

diagnostic criteria, comparable follow-up, and populations,

limiting the ability to meta-analytically pool the results so

as to produce a more robust finding. The limited compari-

sons possible between the age-stratified incidence rates

revealed how studies with differing definitions yield varying

estimates, and the studies did not have consistent conclu-

sions about the associations with age.

Our research on how the prevalence and incidence of MCIhave been variably described over the past 25 years

underscores the large differences in how this condition has

been defined. Similar concerns have been raised regarding

the variation of prevalence estimates published for AD,

which are influenced by both the source of the data and the

diagnostic criteria applied[50]. At the time when these stud-

ies were conducted, the current clinical diagnostic standards

were applied by researchers; however, biomarkers of both

AD and prodromal AD are now increasingly advocated as po-tentially valuable additions to the diagnostic criteria in

research settings[51]. However, the challenge to meaningful

interpretation of the published reports of MCI prevalence and

incidence was also increased by the use of identical terms by

the authors of the published studies, coupled with differences

in the operational approaches. To date, the concept of MCI

has embraced heterogeneous populations, and this currently

imposes a severe limitation on assessment of disease burden

and determination of temporal trends; etiologic research will

also be affected by these discrepancies.

Forfuture population-basedstudies and clinicaltrials, stan-

dardizedclinicaldefinitions for the diagnosis of the prodromalstages of AD, combined with recent progress in the develop-

ment and validation of biomarker-based diagnostic criteria,

have the potential to transform our ability to cross-compare,

interpret findings, and identify variations in the application

of clinical diagnostic criteria [5,52]. Various candidate

biomarkers for supporting the diagnosis of prodromal AD in

patients with aMCI are being evaluated and include a low

cerebrospinal fluid (CSF) amyloid-beta (42) concentration

and a high total-tau/amyloid-beta (42) ratio [51]. For example,

a recent analysis of datacollected during clinicaltrials showed

that only approximately 70% to 74% of aMCI patients with

CSF measures also met these biomarker criteria or had imag-ing for cerebral amyloid burden[53]. Because lumbar punc-

ture to collect CSF is an invasive procedure, this may

decreaseparticipation in population-based studies, and the de-

cision to participate may be influenced by the health status of

the subject, which could potentially lead to selection bias. Ad-

ditional research and validation of potential blood biomarkers

are anticipated to eventually lead to the introduction of tests

that are more suitable for inclusion in routine outpatient diag-

nostic practices, and this will create the opportunity to collect

data from at least a sample of the subjects participating in

population-based studies [5,54,55]. As the understanding

of appropriate selection criteria evolves, or assessmentsof cross-cultural validity and reliability of the various

Table 5

Age-stratified MCI incidence rate (per 1000 person-years)

Study

MCI or synonym

definition

Age category (years)

6569 7074 7579 8084 85

Ravaglia et al, 2008 MCI 49.5 (35.768.6) 69.3 (52.192.2) 93.8 (69.6126.5) 94.9 (61.3147.2) 89.7 (46.7172.4)

Solfrizzi et al, 2004 MCI 3.7 (1.87.7) 9.6 (5.915.7) 55.8 (43.971.2) 46.6 (31.569.0) NR

Busse et al, 2003 aMCI NR NR 5.3 (1.712.4) 14.7 (5.930.4) 8.8 (1.825.6)

Caracciolo, 2008 aMCI NR NR 5.3 (2.212.8) 9.6 (5.815.9) 16.3 (11.323.4)

Larrieu, 2002 aMCI NR 12.4 (11.613.2) 7.7 (7.38.1) 9.5 (8.910.1) 12.4 (11.413.4)



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instruments being used are completed, or other sources of var-

iability are better understood, the design of future population-

based studies may be able to be greatly enhanced.

The lack of standardized definitions suitable for conduct-

ing epidemiological surveys has in the past posed serious

challenges, not only to healthcare planners and development

of policy but also to the design and development of clinicaltrials and to the development of future therapies and inter-

ventions. Standardized definitions for detecting changes ear-

lier in the development of AD, including biomarkers as well

as the various manifestations of cognitive impairment in the

nondemented patient, may provide benefits across all these

dimensions, thereby resulting in improved healthcare for

the patient.

Acknowledgments

This study was sponsored by Elan Pharmaceuticals, Inc

(JANSSEN Alzheimer Immunotherapy acquired the Alz-

heimer Immunotherapy Program from Elan in September

2009).

Alex Ward is an employee of United BioSource Corpora-

tion; Shannon Michels was an employee of United Bio-

Source Corporation at the time of preparation of this

article; and H. Michael Arrighi and Jesse M. Cedarbaum-

were employees of Elan Pharmaceuticals, Inc at the time

this study was conducted.

References

[1] Petersen RC, Smith GE, Waring SC, Ivnik RJ, Tangalos EG,

Kokmen E. Mild cognitive impairment: clinical characterization and

outcome. Arch Neurol 1999;56:3038.

[2] Matthews FE, Stephan BC, McKeith IG, Bond J, Brayne C. Two-year

progression from mild cognitive impairment to dementia: to what ex-

tent do differentdefinitions agree?J Am Geriatr Soc 2008;56:142433.

[3] Petersen RC, Roberts RO, Knopman DS, Boeve BF, Geda YE,

Ivnik RJ,et al. Mild cognitive impairment: tenyears later. Arch Neurol

2009;66:144755.

[4] Petersen RC, Doody R,KurzA, Mohs RC, Morris JC, Rabins PV, et al.

Current concepts in mild cognitive impairment. Arch Neurol 2001;

58:198592.

[5] Winblad B,Palmer K, Kivipelto M, Jelic V, Fratiglioni L, WahlundLO,

et al. Mild cognitive impairmentbeyondcontroversies, towards a con-sensus: report of the International Working Group on Mild Cognitive

Impairment. J Intern Med 2004;256:2406.

[6] Artero S, Ancelin ML, Portet F, Dupuy A, Berr C, Dartigues JF, et al.

Risk profiles for mild cognitive impairment and progression to demen-

tia are gender specific. J Neurol Neurosurg Psychiatry 2008;

79:97984.

[7] Baiyewu O, Unverzagt FW, Ogunniyi A, Hall KS, Gureje O, Gao S,

et al. Cognitive impairment in community-dwelling older Nigerians:

clinical correlates and stability of diagnosis. Eur J Neurol 2002;

9:57380.

[8] Boeve B, McCormick J, Smith G, Ferman T, Rummans T, Carpenter T,

et al. Mild cognitive impairment in the oldest old. Neurology 2003;

60:47780.

[9] Boyle PA, Wilson RS, Aggarwal NT, Tang Y, Bennett DA. Mild

cognitive impairment: risk of Alzheimer disease and rate of cognitive

decline. Neurology 2006;67:4415.

[10] Busse A, Bischkopf J, Riedel-Heller SG, Angermeyer MC. Mild cog-

nitive impairment: prevalence and incidence according to different

diagnostic criteria. Results of the Leipzig Longitudinal Study of the

Aged (LEILA751). Br J Psychiatry 2003;182:44954.

[11] Choi SJ, Jung SS, You YS, Shin BS, Kim JE, Yoon SW, et al. Preva-

lence of Alzheimers dementia and its risk factors in community-

dwelling elderly Koreans. Psychiatry Invest 2008;5:7885.

[12] Coria F, Caso JA, Minguez L, Rodriguez-Artalejo F, Claveria LE.Prevalence of age-associated memory impairment and dementia in

a rural community. J Neurol Neurosurg Psychiatry 1993;56:9736.

[13] Carlo AD, Baldereschi M, Amaducci L, Maggi S, Grigoletto F,

Scarlato G, et al. Cognitive impairment without dementia in older

people: prevalence, vascular risk factors, impact on disability. The

Italian Longitudinal Study on Aging. J Am Geriatr Soc 2000;

48:77582.

[14] Das SK, Bose P, Biswas A, Dutt A, Banerjee TK, Hazra A, et al. An

epidemiologic study of mild cognitive impairment in Kolkata, India.

Neurology 2007;68:201926.

[15] Dubois MF, Hebert R. Cognitive-impairment-free life expectancy for

Canadian seniors. Dement Geriatr Cogn Disord 2006;22:32733.

[16] Fish M, Bayer AJ, Gallacher JE, Bell T, Pickering J, Pedro S, et al.

Prevalence and pattern of cognitive impairment in a community cohort

of men in South Wales: methodology and findings from the Caerphilly

Prospective Study. Neuroepidemiology 2008;30:2533.

[17] Fisk JD, Merry HR, Rockwood K. Variations in case definition affect

prevalence but not outcomes of mild cognitive impairment. Neurology

2003;61:117984.

[18] Ganguli M, Dodge HH, Shen C, DeKosky ST. Mild cognitive impair-

ment, amnestic type: an epidemiologic study. Neurology 2004;

63:11521.

[19] Huang J,Meyer JS, ZhangZ, WeiJ, HongX, Wang J,et al. Progression

of mild cognitive impairment to Alzheimers or vascular dementia ver-

sus normative aging among elderly Chinese. Curr Alzheimer Res

2005;2:5718.

[20] Jungwirth S, Weissgram S, Zehetmayer S, Tragl KH, Fischer P. VITA:

subtypes of mild cognitive impairment in a community-based cohortat

the age of 75 years. Int J Geriatr Psychiatry 2005;20:4528.[21] Kim J, Park MH, Kim E, Han C, Jo SA, Jo I. Plasma homocysteine is

associated with the risk of mild cognitive impairment in an elderly

Korean population. J Nutr 2007;137:20937.

[22] Kivipelto M, Helkala EL, Hanninen T, Laakso MP, Hallikainen M,

Alhainen K, et al. Midlife vascular risk factors and late-life mild cog-

nitive impairment: a population-based study. Neurology 2001;

56:16839.

[23] Koivisto K, Reinikainen KJ, Hanninen T, Vanhanen M, Helkala EL,

Mykkanen L, et al. Prevalence of age-associated memory impairment

in a randomly selected population from eastern Finland. Neurology

1995;45:7417.

[24] Kumamoto T, Sannomiya K, Ueyama H, Aoki K, Nakashima T,

Nakamura R, et al. Neurological abnormalities in cognitively impaired

but not demented elderly. Acta Neurol Scand 2000;102:2928.[25] Kumar R, Dear KB, Christensen H, Ilschner S, Jorm AF,

Meslin C, et al. Prevalence of mild cognitive impairment in 60-

to 64-year-old community-dwelling individuals: the Personality

and Total Health through Life 601 Study. Dement Geriatr Cogn

Disord 2005;19:6774.

[26] Lopez OL, Jagust WJ, DeKosky ST, Becker JT, Fitzpatrick A,

Dulberg C, et al. Prevalence and classification of mild cognitive

impairment in the cardiovascular health study cognition study. Arch

Neurol 2003;60:13859.

[27] Low LF, Brodaty H, Edwards R, Kochan N, Draper B, Trollor J, et al.

The prevalence of cognitive impairmentno dementia in community-

dwelling elderly: a pilot study. Aust N Z J Psychiatry 2004;38:72531.

[28] Manly JJ, Bell-McGinty S, Tang MX, Schupf N, Stern Y, Mayeux R.

Implementing diagnostic criteria and estimating frequency of mild

cognitive impairment in an urban community. Arch Neurol 2005;62:173946.

A. Ward et al. / Alzheimers & Dementia 8 (2012) 142120


8/8

[29] Meguro K, Ishii H, Yamaguchi S, Ishizaki J, Sato M, Hashimoto R,

et al. Prevalence and cognitive performances of clinical dementia rat-

ing 0.5 and mild cognitive impairment in Japan: the tajiri project.

Alzheimer Dis Assoc Disord 2004;18:310.

[30] Pioggiosi PP, Berardi D, Ferrari B, Quartesan R, Ronchi DD. Occur-

rence of cognitive impairment after age 90: MCI and other broadly

used concepts. Brain Res Bull 2006;68:22732.

[31] Plassman BL, Langa KM, Fisher GG, Heeringa SG, Weir DR,Ofstedal MB, et al. Prevalence of cognitive impairment without de-

mentia in the United States. Ann Intern Med 2008;148:42734.

[32] Prencipe M, Santini M, Casini AR, Pezzella FR, Scaldaferri N,

Culasso F. Prevalence of non-dementing cognitive disturbances and

their association with vascular risk factors in an elderly population.

J Neurol 2003;250:90712.

[33] Purser JL, Fillenbaum GG, Pieper CF, Wallace RB. Mild cognitive im-

pairment and 10-year trajectories of disability in the Iowa established

populations for epidemiologic studies of the elderly cohort. J Am Ger-

iatr Soc 2005;53:196672.

[34] Schroder J, Kratz B, Pantel J, Minnemann E, Lehr U, Sauer H. Preva-

lence of mild cognitive impairment in an elderly community sample.

J Neural Transm 1998;54(Suppl):519.

[35] Solfrizzi V, Panza F, Colacicco AM, Introno AD, Capurso C, Torres F,

et al. Vascular risk factors, incidence of MCI, and rates of progression

to dementia. Neurology 2004;63:188291.

[36] Ravaglia G, Forti P, Montesi F, Lucicesare A, Pisacane N, Rietti E,

et al. Mild cognitive impairment: epidemiology and dementia risk in

an elderly Italian population. J Am Geriatr Soc 2008;56:518.

[37] Ronchi DD,Palmer K, PioggiosiP, Atti AR,Berardi D, FerrariB, et al.

The combined effect of age, education, and stroke on dementia and

cognitive impairment no dementia in the elderly. Dement Geriatr

Cogn Disord 2007;24:26673.

[38] Tognoni G, Ceravolo R, Nucciarone B, Bianchi F, DellAgnello G,

Ghicopulos I, et al. From mild cognitive impairment to dementia:

a prevalence study in a district of Tuscany, Italy. Acta Neurol Scand

2005;112:6571.

[39] Unverzagt FW, GaoS, Baiyewu O, Ogunniyi AO, GurejeO, PerkinsA,

et al. Prevalence of cognitive impairment: data from the Indianapolisstudy of health and aging. Neurology 2001;57:165562.

[40] Verghese J, LeValley A, Derby C, Kuslansky G, Katz M, Hall C, et al.

Leisure activities and the risk of amnestic mild cognitive impairment

in the elderly. Neurology 2006;66:8217.

[41] Caracciolo B, Palmer K, Monastero R, Winblad B, Backman L,

Fratiglioni L. Occurrence of cognitive impairment and dementia in

the community: a 9-year-long prospective study. Neurology 2008;

70(19 Pt 2):177885.

[42] Hsiung GY, Sadovnick AD, Feldman H. Apolipoprotein E epsilon4

genotype as a risk factor for cognitive decline and dementia: data

from the Canadian Study of Health and Aging. CMAJ 2004;

171:8637.

[43] Larrieu S, Letenneur L, Orgogozo JM, Fabrigoule C, Amieva H,

Carret NL, et al. Incidence and outcome of mild cognitive impair-

ment in a population-based prospective cohort. Neurology 2002;

59:15949.

[44] Manly JJ, Tang MX, Schupf N, Stern Y, Vonsattel JP, Mayeux R. Fre-

quency and course of mild cognitive impairment in a multiethnic com-munity. Ann Neurol 2008;63:494506.

[45] Tervo S, Kivipelto M, Hanninen T, Vanhanen M, Hallikainen M,

Mannermaa A, et al. Incidence and risk factors for mild cognitive im-

pairment: a population-based three-year follow-up study of cogni-

tively healthy elderly subjects. Dement Geriatr Cogn Disord 2004;

17:196203.

[46] Tuokko H, Frerichs R, Graham J, Rockwood K, Kristjansson B, Fisk J,

et al. Five-year follow-up of cognitive impairment with no dementia.

Arch Neurol 2003;60:57782.

[47] Wilson RS, Schneider JA, Arnold SE, Tang Y, Boyle PA,

Bennett DA. Olfactory identification and incidence of mild cogni-

tive impairment in older age. Arch Gen Psychiatry 2007;

64:8028.

[48] Bischkopf J, Busse A, Angermeyer MC. Mild cognitive impairment

a review of prevalence, incidence and outcome according to current

approaches. Acta Psychiatr Scand 2002;106:40314.

[49] Petersen RC.Mild cognitive impairment as a diagnostic entity. J Intern

Med 2004;256:18394.

[50] Lin PJ, Kaufer DI, Maciejewski ML, Ganguly R, Paul JE,

Biddle AK. An examination of Alzheimers disease case defini-

tions using Medicare claims and survey data. Alzheimers Dement

2010;6:33441.

[51] Dubois B, Feldman HH, Jacova C, Dekosky ST, Barberger-Gateau P,

Cummings J, et al. Research criteria for the diagnosis of Alzheimers

disease: revising the NINCDS-ADRDA criteria. Lancet Neurol 2007;

6:73446.

[52] Blennow K, Hampel H, Weiner M, Zetterberg H. Cerebrospinal fluid

and plasma biomarkers in Alzheimer disease. Nat Rev Neurol 2010;

6:13144.[53] Schneider LS, Kennedy RE, Cutter GR. Requiring an amyloid-beta(1-

42) biomarker for prodromal Alzheimers disease or mild cognitive

impairment does not lead to more efficient clinical trials. Alzheimers

Dement 2010;6:36777.

[54] Blennow K, Zetterberg H. Is it time for biomarker-based diagnostic

criteria for prodromal Alzheimers disease? Alzheimers Res Ther

2010;2:8.

[55] Schneider LS. The potential and limits for clinical trials for early Alz-

heimers disease and some recommendations. J Nutr Health Aging

2010;14:2958.


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