Leipzig Longitudinal Study of the Aged LEILA75+, Department of Psychiatry, University of Leipzig, Germany
Correspondence: Professor Steffi G. Riedel-Heller, MPH, Department of Psychiatry, University of Leipzig, Johannisallee 20, 04317 Leipzig, Germany. Tel.: +49 341 97 24 530; fax: +49 341 97 24 539. Email: ries{at}medizin.uni-leipzig.de
Declaration of interest None. Funding detailed in Acknowledgements.
* Results of the Leipzig Longitudinal Study of the Aged (LEILA75+) ![]()
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Aims This study examines the time-dependent evolution from mild cognitive impairment to dementia. Current assumptions regarding yearly and lifetime conversion rates are challenged.
Method A community sample of 1045 dementia-free individuals aged 75 years and over was examined by neuropsychological testing based on 6 years of observation.
Results Approximately 6065% of people with mild cognitive impairment develop clinical dementia during their life. Progression from mild cognitive impairment to dementia appears to be time dependent, occurring primarily within the initial 18 months.
Conclusions Further long-term studies are needed to examine the time-dependent evolution from mild cognitive impairment to dementia and to establish age-specific conversion rates during lifetime.
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Of the overall sample of 1692 persons, 242 (14.3%) declined to participate,
57 (3.4%) had died and 15 (0.9%) were not traceable. Information on 113
members of the study sample (6.7%) who were shielded by their relatives was
obtained solely by proxy interviews. Clinical interviews incorporating
neuropsychological assessment were conducted with 1265 (74.8%) people who did
not differ significantly from the remainder of the sample in terms of age
(U=263 553, P=0.455), gender (
2=0.391,
d.f.=1, P=0.532) or marital status (
2=5.027, d.f.=3,
P=0.170). Of these 1265 people, 220 (17.4%) had dementia according to
DSMIV criteria (American Psychiatric
Association, 1994). This analysis was based on the remaining 1045
without dementia.
Instruments
The main instrument used was the Structured Interview for Diagnosis of
Dementia of Alzheimer-type, Multi-infarct Dementia and Dementia of other
Aetiology according to ICD10 (World
Health Organization, 1992) and DSMIV (SIDAM;
Zaudig et al, 1991).
The SIDAM consists of a neuropsychological test battery including the
Mini-Mental State Examination (MMSE;
Folstein et al, 1975),
a section for clinical judgement and third-party information on psychosocial
impairment. The neuropsychological test battery of the SIDAM covers six areas
of neuropsychological functioning:
For each cognitive domain, age-specific and education-specific norms were used in the evaluation of impairment in cognitive function. The norms were developed from the baseline population (participants without dementia) from which the study sample was recruited (Busse et al, 2002).
Data on socio-demographic variables and possible risk factors for dementia and mild cognitive impairment were collected. A series of validated scales examining the capacity to perform a wide range of activities of daily living, such as use of telephone, feeding, dressing and personal hygiene, were completed. Complaints of subjective memory impairment were assessed before cognitive testing by asking participants if they had any problems with their memory (answer yes or no). Depressive symptoms were assessed by means of the Center for Epidemiological Studies Depression scale (CESD; Radloff, 1977) and the Structured Clinical Interview for DSMIIIR (SCID; Spitzer et al, 1987).
Data collection
Structured clinical interviews were conducted by trained psychologists and
physicians during visits to the participants homes. In addition,
structured third-party interviews were conducted to obtain information on
cognitive and psychosocial functioning and subjective memory impairment.
Baseline interviews were conducted between January 1997 and June 1998. Study
participants were requested to take part in four follow-up assessments, which
were conducted 1.5 years, 3 years, 4.5 years and 6 years after the baseline
assessment.
If it was not possible to administer the SIDAM at follow-up (e.g. owing to death or severe weakness, or because relatives refused participation on behalf of the elderly person in their care), we offered the option of a fully structured proxy interview. This included the Clinical Dementia Rating scale (CDR; Hughes et al, 1982) for assessment of cognitive functioning.
Study participants were followed until death or onset of dementia or for a maximum of 6 years if the SIDAM could be administered at each follow-up assessment. As long as the SIDAM could be administered to apply diagnostic criteria of mild cognitive impairment and dementia, participants remained in the study. If participants refused further participation, or if there was not sufficient information to apply diagnostic criteria of mild cognitive impairment or dementia, they were excluded from the study. The statistical analysis for these was based on the diagnosis established at the last follow-up visit at which the participant had undergone cognitive testing. In case of death or onset of dementia, the diagnostic criteria of dementia were applied based on CDR data or based on the SIDAM.
Definition of mild cognitive impairment
Consensus conferences of physicians and psychologists were held for each
participant. The clinical diagnosis of dementia was made according to
DSMIV criteria.
According to Petersen (2004b), four subtypes of mild cognitive impairment were examined:
In the following analysis, mild cognitive impairment was diagnosed if diagnostic criteria of one of the four subtypes was fulfilled. All four subtypes of mild cognitive impairment also had to meet the following criteria:
In addition to the cut-off of 1.0 s.d. used to define cognitive impairment (mild cognitive impairment original 1.0 s.d.), a cut-off of 1.5 s.d. was also used to capture only the more severely affected individuals (mild cognitive impairment original 1.5 s.d.). Furthermore, we introduced slightly modified criteria by excluding the first criterion (the presence of a complaint) from the necessary diagnostic criteria on memory (mild cognitive impairment 1.0 modified, mild cognitive impairment 1.5 modified). The importance of subjective memory impairment in the prediction of dementia is subject to debate. Some authors suggest that memory complaints may not be of additional predictive value (Jorm et al, 1997), others have shown that memory complaints are an important predictor for progressive cognitive decline (Comijs et al, 2004).
People with a diagnosis of Parkinsons disease, learning disability and brain cancer, or severe weakness or severe sensory impairment impairment leading to invalid cognitive testing were excluded from the study, whereas persons with depression or stroke were not excluded.
Analysis
In order to analyse possible non-response bias,
2 analysis
and the MannWhitney U-test were applied. For all analyses, an
level of 0.01 was used. Descriptive statistics were used for the
demographic variables. Cumulative numbers of people and cumulative percentages
(related to the number of participants at each follow-up) are given for each
point of assessment to illustrate the time-dependent progression of mild
cognitive impairment to dementia or death. Estimation of the maximum
conversion rate of mild cognitive impairment to dementia during life is based
on the conservative assumption that all individuals with mild cognitive
impairment who are still alive after 6 years without dementia will develop
dementia later.
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Baseline characteristics of the total study sample are given in Table 1. The study population had a mean age of 81.5 years (s.d.=4.8). Three-quarters of the sample were women. The mean MMSE score was 27 points.
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View this table: [in a new window] | Table 1 Demographic characteristics of the baseline population according to different diagnostic criteria of mild cognitive impairment |
![]() View larger version (32K): [in a new window] [as a PowerPoint slide] |
Fig. 1 Number of study participants at baseline and at follow-up with mild
cognitive impairment (MCI; Petersen, 2004) according to different diagnostic
criteria: (a) MCI 1.5 s.d. modified; (b) MCI 1.5 s.d. original; (c) MCI 1.0
s.d. modified; (d) MCI 1.0 s.d. original. , MCI;
, drop-out.
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Examination at follow-up
After baseline examination, 117 (11.9%) participants had to be excluded
from analysis because they refused further participation, or there was not
sufficient information to apply diagnostic criteria of mild cognitive
impairment or dementia. These 117 participants did not differ significantly
from the remainder of the sample (n=863, 88.1%) in age
(U=46491, P=0.164), gender (
2=5.551, d.f.=1,
P=0.058), education (
2=3.268, d.f.=2,
P=0.195) or complaints of impaired memory expressed by the individual
or significant others at the baseline assessment (
2=4.781,
d.f.=3, P=0.189). However, drop-outs had a significantly lower MMSE
score at baseline (U=41597, P=0.002). Drop-out rates
reported in Table 1 suggest
that drop-out was slightly higher in the groups with mild cognitive impairment
than in the total study population. However, comparing drop-outs in the mild
cognitive impairment group with drop-outs in the corresponding non-mild
cognitive impairment group for each of the investigated concepts, we found
that mild cognitive impairment drop-outs and non-mild cognitive impairment
drop-outs did not differ significantly in age, gender, education and MMSE
score at baseline.
![]() View larger version (24K): [in a new window] [as a PowerPoint slide] |
Fig. 2 Cumulative percentages for different outcomes of people with (a) non-mild
and (b) mild cognitive impairment at baseline related to the total number of
participants who remained in the study at each follow-up assessment.
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Outcome of mild cognitive impairment at each follow-up assessment over 6 years
Figure 1 shows the
cumulative number for each follow-up assessment of study participants who
developed dementia, died without a diagnosis of dementia, were alive without a
dementia diagnosis or refused further participation.
Figure 2 shows the cumulative percentages of participants who developed dementia, died without a diagnosis of dementia or were alive without dementia diagnosis, related to the total number of participants who remained in the study at each follow-up assessment.
After 6 years of observation, about 50% of the participants who did not meet diagnostic criteria of mild cognitive impairment at baseline (non-mild cognitive impairment), and underwent further follow-up assessment, were still alive without a diagnosis of dementia; about 30% died; and about 20% developed dementia. At each follow-up assessment, the proportion of participants who died without ever having a diagnosis of dementia was higher than the proportion of participants who developed dementia (Fig. 2a).
Participants who fulfilled diagnostic criteria of mild cognitive impairment at baseline, and underwent further follow-up assessment, had different outcomes. At each follow-up assessment, the proportion of participants who developed dementia was higher than the proportion who died without ever having a diagnosis of dementia. Irrespective of which diagnostic cut-off for mild cognitive impairment was applied (modified or original criteria, 1.0 or 1.5 s.d.), the proportion of participants with mild cognitive impairment who developed dementia was highest during the first 18 months of observation (between 14% and 23%). Of participants who met modified criteria for mild cognitive impairment (1.0 s.d.), 14% developed dementia within the first 18 months of observation, but at further follow-ups only 79% did so. Participants who fulfilled the other three diagnostic concepts of mild cognitive impairment had a progression rate to dementia of about 20% within the first 18 months of observation, which reduced to 10% at further follow-up. After 6 years of observation, only about 20% of participants with mild cognitive impairment at baseline were still alive without a diagnosis of dementia, about 30% died without dementia, and about 50% developed dementia (Fig. 2b).
Estimation of the maximum conversion rate during life
If we tried to estimate the maximum conversion rate to dementia in
participants with mild cognitive impairment, we would assume it to be about
65%. According to the mild cognitive impairment modified criteria (1.5 s.d.),
only 22 participants were still alive without a diagnosis of dementia after 6
years (Fig. 1). If all 22
participants developed dementia at follow-up, 78 (56+22) people (65%) would
have developed dementia and 42 participants (35%) would have died without a
diagnosis of dementia. Similarly, according to the mild cognitive impairment
original criteria (1.5 s.d.), after 6 years only 7 participants were still
alive without a diagnosis of dementia. If all 7 participants developed
dementia at follow-up, 42 (35+7) people (68%) would have developed dementia
and 20 participants (32%) would have died without a diagnosis of dementia.
Since some of the 22 (mild cognitive impairment modified criteria, 1.5 s.d.)
or 7 (mild cognitive impairment original criteria, 1.5 s.d.) would have died
without a diagnosis of dementia, we could say that a maximum of 6065%
of people with mild cognitive impairment, who were 75 years or older, would
develop clinical dementia.
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Furthermore, our results suggest that people with mild cognitive impairment, who are aged 75 years or older, develop clinical dementia during their lifetime at a rate of approximately 6065%. In contrast, Petersen (2003) reports that after approximately 6 years 80% of the mild cognitive impairment cohort has progressed to dementia; he further assumes that the final numbers may extend to 8090%. These results are based on clinical studies in which participants might be more impaired than in population-based samples. In addition, study participants were younger than in our study.
Long-term studies are prone to selection bias by attrition. Drop-outs from the groups with and without mild cognitive impairment did not differ significantly in age, gender, education or MMSE score at baseline. However, selective attrition may still have occurred with regard to further characteristics. In the calculation of the maximum conversion rate, we used a very conservative approach to minimise any potential problem. This paper focuses on the time-dependency time-dependency of progression of mild cognitive impairment to dementia. As indicated in Fig. 1, attrition happened gradually and therefore may not obscure the time-dependent pattern.
Studies are needed where people with mild cognitive impairment in different age-groups are followed until their death. Such studies could examine the proportion of people with mild cognitive impairment developing dementia and the proportion dying without a diagnosis of dementia. Age-specific conversion rates of mild cognitive impairment to dementia should be established.
Precise knowledge about age-specific conversion rates of mild cognitive impairment to dementia is essential to make an evidence-based prognosis for people with mild cognitive impairment at a specific age, and to assist in service planning that would include health-economic considerations.
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