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Aging and disease    2019, Vol. 10 Issue (1) : 1-11     DOI: 10.14336/AD.2018.0123
Orginal Article |
Is Dementia More Fatal Than Previously Estimated? A Population-based Prospective Cohort Study
Jong Bin Bae1, Ji Won Han2, Kyung Phil Kwak3, Bong Jo Kim4, Shin Gyeom Kim5, Jeong Lan Kim6, Tae Hui Kim7, Seung-Ho Ryu8, Seok Woo Moon9, Joon Hyuk Park10, Jong Chul Youn11, Dong Young Lee1,12, Dong Woo Lee13, Seok Bum Lee14, Jung Jae Lee14, Jin Hyeong Jhoo15, Ki Woong Kim1,2,16,*
1Department of Psychiatry, Seoul National University College of Medicine, Seoul, Korea.
2Department of Neuropsychiatry, Seoul National University Bundang Hospital, Gyeonggido, Korea.
3Department of Psychiatry, Dongguk University Gyeongju Hospital, Gyeongju, Korea.
4Department of Psychiatry, Gyeongsang National University, School of Medicine, Jinju, Korea.
5Department of Neuropsychiatry, Soonchunhyang University Bucheon Hospital, Bucheon, Korea.
6Department of Psychiatry, School of Medicine, Chungnam National University, Daejeon, Korea.
7Department of Psychiatry, Yonsei University Wonju Severance Christian Hospital, Wonju, Korea.
8Department of Psychiatry, School of Medicine, Konkuk University, Konkuk University Medical Center, Seoul, Korea.
9Department of Psychiatry, School of Medicine, Konkuk University, Konkuk University Chungju Hospital, Chungju, Korea.
10Department of Neuropsychiatry, Jeju National University Hospital, Jeju, Korea.
11Department of Neuropsychiatry, Kyunggi Provincial Hospital for the Elderly, Korea.
12Department of Neuropsychiatry, Seoul National University Hospital, Seoul, Korea.
13Department of Neuropsychiatry, Inje University Sanggye Paik Hospital, Seoul, Korea.
14Department of Psychiatry, Dankook University Hospital, Cheonan, Korea.
15Department of Neuropsychiatry, Kangwon National University Hospital, Korea.
16Department of Brain and Cognitive Science, Seoul National University College of Natural Sciences, Seoul, Korea.
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Dementia increases the risk of mortality (ROM) in the elderly and estimates of hazard ratio (HR) of dementia for mortality have ranged from 1.7 to 6.3. However, previous studies may have underestimated ROM of dementia due to length bias, which occurs when failing to include the persons with rapidly progressive diseases, who died before they could be included in the study. This population-based prospective cohort study conducted on 6,752 randomly sampled Koreans, aged 60 years or older (the Korean Longitudinal Study on Cognitive Aging and Dementia). Cognitive disorders were evaluated at baseline and 2-year follow-up using the Korean version of the Consortium to Establish a Registry for Alzheimer’s Disease Assessment Packet (CERAD-K), and prevalent and incident cases of dementia were identified. The participants’ deaths were confirmed through the National Mortality Database of Statistics Korea. We compared the ROM between prevalent and incident dementia, and estimated HR of dementia for mortality using Cox proportional hazards model. Of the 5,097 responders to the 2-year follow-up assessment, 150 participants had dementia from the baseline (prevalent dementia), and 95 participants developed dementia during the 2-year follow-up period (incident dementia). The ROM of participants with incident dementia was about 3 times higher than the ROM of those with prevalent dementia (HR = 3.04, 95% confidence interval [CI] = 1.34-6.91). Compared to cognitively normal participants at both the baseline and 2-year follow-up assessments, the ROM of those with incident dementia approximately 8 times higher (HR = 8.37, 95 % CI = 4.23-16.54). In conclusion, the ROM of dementia using prevalent cases was underestimated due to length bias, and dementia may be much more fatal than previously estimated. In clinical settings, the ROM of dementia warrants the attention of physicians, particularly in recently incident dementia cases.

Keywords dementia      Alzheimer’s disease      mortality      death      survival     
Corresponding Authors: Kim Ki Woong   
Issue Date: 28 December 2017
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Bae Jong Bin
Han Ji Won
Kwak Kyung Phil
Kim Bong Jo
Kim Shin Gyeom
Kim Jeong Lan
Kim Tae Hui
Ryu Seung-Ho
Moon Seok Woo
Park Joon Hyuk
Youn Jong Chul
Lee Dong Young
Lee Dong Woo
Lee Seok Bum
Lee Jung Jae
Jhoo Jin Hyeong
Kim Ki Woong
Cite this article:   
Bae Jong Bin,Han Ji Won,Kwak Kyung Phil, et al. Is Dementia More Fatal Than Previously Estimated? A Population-based Prospective Cohort Study[J]. Aging and disease, 2019, 10(1): 1-11.
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Figure 1.  The estimated risks of mortality of dementia according to the interval and duration of follow-up. *Estimated using Cox proportional hazard models and compared to non-demented participants; the error bars indicate 95% confidence. The references are as follows: [2-5, 7-9, 12-20].
Figure 2.  The flowchart of the mortality analysis in the Korean Longitudinal Study on Cognitive Aging and Dementia. MCI = mild cognitive impairment.
Baseline characteristicsRespondersNon-respondersStatistics*
T or χ2p
Normal cognition
Age (years ± SD)68.9 ± 6.169.2 ± 6.4-1.1080.268
Sex (men, %)44.845.70.1970.657
Education (years ± SD)8.9 ± 5.38.1 ± 5.34.312< 0.001
Smoking status (yes, %)
Alcohol consumption (yes, %)
MHIS (score ± SD)0.7 ± 0.90.6 ± 0.71.5110.131
CIRS score (score ± SD)4.3 ± 2.83.9 ± 2.54.176< 0.001
Depression (yes, %)
Mild cognitive impairment
Age (years ± SD)71.8 ± 6.772.4 ± 8.0-1.3520.177
Sex (men, %)38.535.51.3000.254
Education (years ± SD)6.9 ± 5.05.7 ± 4.84.590< 0.001
Smoking status (yes, %)26.924.60.8720.350
Alcohol consumption (yes, %)28.324.52.3540.125
MHIS (score ± SD)0.9 ± 1.10.9 ± 1.2-0.9190.358
CIRS score (score ± SD)4.9 ± 2.94.6 ± 3.01.4740.141
Depression (yes, %)
Age (years ± SD)77.9 ± 7.979.7 ± 7.7-1.9570.051
Sex (men, %)
Education (years ± SD)3.8 ± 4.53.3 ± 4.40.8000.424
Smoking status (yes, %)20.422.20.1230.726
Alcohol consumption (yes, %)
MHIS (score ± SD)1.5 ± 1.91.7 ± 2.6-1.0170.310
CIRS score (score ± SD)4.9 ± 2.85.7 ± 3.7-1.9720.050
Depression (yes, %)
Age (years ± SD)70.0 ± 6.671.1 ± 7.7-5.322< 0.001
Sex (men, %)42.840.62.2860.131
Education (years ± SD)8.2 ± 5.46.9 ± 5.38.615< 0.001
Smoking status (yes, %)29.628.20.9860.321
Alcohol consumption (yes, %)
MHIS (score ± SD)0.7 ± 1.00.8 ± 1.2-2.1910.029
CIRS score (score ± SD)4.5 ± 2.84.3 ± 2.92.3230.020
Depression (yes, %)
Table 1  Baseline characteristics of the responders and non-responders, at the 2-year follow-up assessment.
DiagnosisTypeNumber of participantsPerson-yearsNumber of deathsHR (95% CI)*
DementiaPrevalent cases150251.8131.00
Incident cases95158.5153.04 (1.34 - 6.91)
Alzheimer’s diseasePrevalent cases117201.591.00
Incident cases67118.092.90 (1.06 - 7.97)
Mild cognitive impairmentPrevalent cases7441285.0231.00
Incident cases502848.5171.24 (0.65 - 2.34)
Table 2  Comparison of the mortality risks between prevalent and incident cases.
Figure 3.  Kaplan-Meier survival curves of the prevalent and incident cases with dementia.
DiagnosisNo. of participantsDeaths
Person-yearsNo.HR (95% CI)*
NC at both baseline and follow-up30795406.6281.00
Prevalent MCI7441285.0231.94 (1.06 - 3.52)
Incident MCI502848.5172.22 (1.14 - 4.30)
Prevalent dementia§150251.8132.82 (1.28 - 6.22)
Incident dementia§§95158.5158.37 (4.23 - 16.54)
Not demented at both baseline and follow-up48498494.1791.00
Prevalent dementia§150251.8131.82 (0.90 - 3.69)
Incident dementia§§95158.5155.53 (3.06 - 9.98)
Table 3  The risk of mortality according to the diagnosis at baseline and 2-year follow-up assessment.
(year of publication)
(F, %)
DiagnosisReference groupHR of dementia
(or AD)
of follow-up
Follow-up assessmentInterval of follow-up assessment (years)
Aguero-Torres et al.
98977+77Incident dementiaNon-demented2.0 (1.5-2.7)5.0Yes3.4
Aevarsson et al.
49495+71Prevalent dementia,
Non-demented2.6 (male) 2.9 (female)7.0No
Baldereschi et al.
563265+49Prevalent dementiaNon-demented3.56 (2.52-5.04)2.3No
Helmer et al.
377765+Incident dementiaNon-demented1.80 (1.46-2.21)8.0Yes2.2
Noale et al.
563265+49Prevalent dementiaNon-demented3.72 (3.01-4.60)4.0No
Tschanz et al.
468365+57Prevalent dementiaNon-demented2.99 (2.53-3.53)5.0No
Fitzpatrick et al.
360265+59Incident dementia,
Non-dementedDementia: 2.8 (2.3-3.4)
AD: 2.1 (1.6-2.7)
Nitrini et al.
195665+Prevalent dementiaNon-demented3.92 (2.80-5.48)4.0No
Ganguli et al.
168165+58Prevalent AD
+ Incident AD
Non-demented1.7 (1.4-2.0)10.3Yes2.0
Guhne et al.
112475+75Incident dementiaNon-demented2.42 (1.62-3.63)4.5Yes1.6
Scarmeas et al.
33865+78Prevalent ADNon-demented2.38 (1.86-3.04)4.4No
Llinàs-Regla et al.
115370+57Prevalent dementiaNon-demented2.3 (1.7-3.2)4.3No
Wilson et al.
171565+62Prevalent ADNormal cognition2.84 (2.29-3.52)4.7No
Villarejo et al.
526265+58Prevalent dementiaNon-demented3.16 (2.74-3.65)13No
Wu et al.
2788Prevalent dementiaNon-demented2.18 (1.75-2.71)7.3No
James et al.
256665+72Incident ADNon-demented3.13 (2.74-3.58)8.0Yes1.0
Chen et al.
297860+Prevalent dementiaNon-demented2.69 (2.11-3.42)5.0No
Park et al.
103565+58Prevalent dementiaNormal cognition3.20 (2.30-4.44)8.0No
Paddick et al.
119870+71Prevalent dementiaNormal cognition6.33 (3.19-12.58)4.0No
Table 4  Studies investigating the risk of mortality of dementia or Alzheimer’s disease.
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