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Risk Factor:
Risk Factor Type: Medical history
Current Understanding:
The evidence from observational epidemiologic studies provide some support for a harmful effect of head injuries, with risk especially elevated among those whose head injuries occur later in life or are more severe. However, few prospective studies have been conducted on head injury and AD, and they have significant methodological limitations. More importantly, the diagnosis of dementia in all prior studies has been based on clinical features rather than modern biomarker assays to identify the dementia subtype, and there have been no studies where the clinical diagnosis of AD was confirmed in pathologic studies. Thus, while head injury likely increases the risk of developing dementia, epidemiologic evidence linking head injury to AD dementia is less clear. There is much greater support for moderate to severe head injury in total dementia, and some support for mild head injury with loss of consciousness and total dementia. Of course, as there are many other harmful effects from head injury, there is ample support for current efforts to prevent head injuries. Moreover, the question of the impact of small recurrent injuries is under active investigation, and additional recommendations may emerge for youth, recreational, and professional sports and other activities in which these injuries are common. Prospective cohort studies are needed of individuals following TBI, with careful clinical evaluation and the addition of modern neuroimaging and biomarker tools and neuropathologic confirmation whenever possible. For a review of the putative mechanisms by which head injury may influence AD risk and detailed commentary on interpreting the findings below in a broader context, please view the Discussion.
Literature Extraction: Search strategy  * New *
Last Search Completed: 06 July 2011 - Last content update released on 17 Aug 2012.


Table 1:   Head injury with loss of consciousness (ever vs. never)
Notes These studies examine the association between a history of head injury involving loss of consciousness and AD risk. Each study ascertained the history of head injury slightly differently, and these differences are briefly described in the exposure detail for each study.  
  Alzheimer Disease Total Dementia  
Paper Cohort Study Type # Subjects
(% Female)
Average Follow-up Time Exposure Distribution
# of Cases Effect Size 95% CI P-value # of Cases Effect Size 95% CI P-value Ethnicity Age at Start of Follow-up:
Mean (SD)
(Range)
Diagnostic Assessment Covariates & Analysis Comment Paper
Launer, 1999 EURODEM Incidence study reporting incidence rate ratios via Poisson regression (IRRs) 12934
(57%)
2.2 y
*
No head injury with loss of consciousness: 91%
Head injury with loss of consciousness: 9%
(detail)
306
27
Total: 333
1.00
1.02
Ref.
0.68-1.51
Ref.
0.92
*
450
45
Total: 495
1.00
1.14
Ref.
-
Ref.
0.4
*
Caucasian
(detail)
- (-)
(65 - )
Screening: CAMDEX, GMS, MMSE

AD Diagnosis: NINCDS ADRDA
(detail)
A, E, G, O, SP‡
(detail)
Launer, 1999
Mehta, 1999 Rotterdam Study Cumulative incidence study reporting odds ratios (ORs) 6645
(59%)
2.1 y
(detail)
No head injury with loss of consciousness: 88%
Head injury with loss of consciousness: 12%
(detail)
85
6
Total: 91
1.00
0.80
Ref.
0.40-1.90
Ref.
0.57
*
118
11
Total: 129
1.00
1.00
Ref.
0.50-2.00
Ref.
1.0
*
Caucasian
(detail)
69 (9)
(55 - )
Screening: CAMDEX, GMS, MMSE

AD Diagnosis: NINCDS ADRDA
(detail)
A, E, G‡ Mehta, 1999
Plassman, 2000 World War II Navy and Marine veterans Cohort study reporting odds ratios (ORs) 1776
(0%)
-
(detail)
No head injury with loss of consciousness: 69%
Head injury with loss of consciousness: 31%
(detail)
18
17
Total: 35
1.00
2.01
Ref.
1.03-3.91
Ref.
0.04
*
26
28
Total: 54
1.00
2.23
Ref.
1.30-3.81
Ref.
0.004
*
Caucasian, Other, African-American (Black)
- (-)
( - )
(detail)
Screening: DQ, IQ-CODE, TICS

AD Diagnosis: NINCDS ADRDA
(detail)
A, E‡
(detail)
Plassman, 2000
Schofield, 1997 WHICAP Incidence study reporting hazard ratios (HRs) 271
(73%)
1.7 y
(detail)
Head injury ascertained by interviewer
No head injury with loss of consciousness: 88%
Head injury with loss of consciousness: 10%
(detail)

34
4
Total: 38

1.00
1.90†

Ref.
0.60-5.80

Ref.
0.27
*

41
6
Total: 47

1.00
2.10

Ref.
0.80-5.30

Ref.
0.12
*
Caucasian, Hispanic, African-American (Black)
75 (7)
(60 - )
Screening: CDR

AD Diagnosis: NINCDS ADRDA
(detail)
A, E, G, O‡§
(detail)
Schofield, 1997
Schofield, 1997 WHICAP Incidence study reporting hazard ratios (HRs) 271
(73%)
1.7 y
(detail)
Head injury ascertained by physician
No head injury with loss of consciousness: 88%
Head injury with loss of consciousness: 7%
(detail)

34
4
Total: 38

1.00
3.60†

Ref.
1.20-11.20

Ref.
0.02
*

41
5
Total: 46

1.00
3.20†

Ref.
1.20-8.60

Ref.
0.02
*
Caucasian, Hispanic, African-American (Black)
75 (7)
(60 - )
Screening: CDR

AD Diagnosis: NINCDS ADRDA
(detail)
A, E, G, O‡§
(detail)
Schofield, 1997
* Derived value.
† Five or fewer cases exist.
‡ Covariates: "A" (age), "E" (education), "G" (gender), "O" (other), "SP" (study population)
§ Covariates for total dementia are different.
 
Table 2:   Head injury with loss of consciousness, by severity
Notes These studies examine risk of AD in association with a history of head injury involving loss of consciousness, according to degree of severity. Each study describes severity differently, based on length of loss of consciousness, presence of skull fracture, presence of amnesia, and/or number of head injuries.  
  Alzheimer Disease Total Dementia  
Paper Cohort Study Type # Subjects
(% Female)
Average Follow-up Time Exposure Distribution
# of Cases Effect Size 95% CI P-value # of Cases Effect Size 95% CI P-value Ethnicity Age at Start of Follow-up:
Mean (SD)
(Range)
Diagnostic Assessment Covariates & Analysis Comment Paper
Mehta, 1999 Rotterdam Study Cumulative incidence study reporting odds ratios (ORs) 6645
(59%)
2.1 y
(detail)
No head injury with loss of consciousness: 88%
1 head injury w/ loss of consciousness: 11%
>1 head injury w/ loss of consciousness: 2%
Head injury w/ loss of consciousness ≤ 15 minutes: 7%
Head injury w/ loss of consciousness > 15 minutes: 2%
(detail)
85
-
-
-
-
Total: 91
1.00
0.80
1.00
-
0.40
Ref.
0.30-2.00
0.10-7.60
-
0.10-1.80
Ref.
0.64
1.0
-
0.21
*
118
-
-
-
-
Total: 129
1.00
0.90
1.40
0.40
1.70
Ref.
0.50-1.90
0.30-6.00
0.10-1.40
0.50-5.40
Ref.
0.76
0.76
0.17
0.38
*
Caucasian
(detail)
69 (9)
(55 - )
Screening: CAMDEX, GMS, MMSE

AD Diagnosis: NINCDS ADRDA
(detail)
A, E, G‡ Mehta, 1999
Plassman, 2000 World War II Navy and Marine veterans Cohort study reporting odds ratios (ORs) 1776
(0%)
-
(detail)
No head injury with loss of consciousness: 69%
Head injury with loss of consciousness, mild:         
Head injury with loss of consciousness, moderate:         
Head injury with loss of consciousness, severe:         
(detail)
18
-
-
-
Total: 35
1.00
0.76
2.32
4.51
Ref.
0.18-3.29
1.04-5.17
1.77-11.47
Ref.
0.71
0.04
0.002
*
26
-
-
-
Total: 54
1.00
1.33
2.39
4.48
Ref.
0.51-3.47
1.24-4.58
2.09-9.63
Ref.
0.56
0.009
0.0001
*
Caucasian, Other, African-American (Black)
- (-)
( - )
(detail)
Screening: DQ, IQ-CODE, TICS

AD Diagnosis: NINCDS ADRDA
(detail)
A, E‡
(detail)
Plassman, 2000
Schofield, 1997 WHICAP Incidence study reporting hazard ratios (HRs) 271
(73%)
1.7 y
(detail)
Head injury ascertained by interviewer
No head injury with loss of consciousness: 88%
Head injury w/ loss of consciousness < 5 minutes: 5%
Head injury w/ loss of consciousness ≥ 5 minutes: 2%
(detail)

34
-
-
Total: 34

1.00
1.70
11.20

Ref.
0.40-7.50
2.30-59.80

Ref.
0.48
0.004
*

 
 
 

 

 

 
Caucasian, Hispanic, African-American (Black)
75 (7)
(60 - )
Screening: CDR

AD Diagnosis: NINCDS ADRDA
(detail)
A, E, G‡
(detail)
Schofield, 1997
* Derived value.
‡ Covariates: "A" (age), "E" (education), "G" (gender)
 
Table 3:   Head injury with loss of consciousness, by timing
Notes These studies examine risk of AD in association with a history of head injury involving loss of consciousness, according to when in life the head injury occurred.  
  Alzheimer Disease Total Dementia  
Paper Cohort Study Type # Subjects
(% Female)
Average Follow-up Time Exposure Distribution
# of Cases Effect Size 95% CI P-value # of Cases Effect Size 95% CI P-value Ethnicity Age at Start of Follow-up:
Mean (SD)
(Range)
Diagnostic Assessment Covariates & Analysis Comment Paper
Mehta, 1999 Rotterdam Study Cumulative incidence study reporting odds ratios (ORs) 6645
(59%)
2.1 y
(detail)
Head injury with loss of consciousness
None: 88%
Latency ≤ 10 years: 2%
Latency > 10 years: 10%
(detail)

85
-
-
Total: 91

1.00
1.40
0.70

Ref.
0.30-6.30
0.20-1.80

Ref.
0.66
0.52
*

118
-
-
Total: 129

1.00
1.10
1.00

Ref.
0.30-6.40
0.50-2.00

Ref.
0.9
1.0
*
Caucasian
(detail)
69 (9)
( - )
Screening: CAMDEX, GMS, MMSE

AD Diagnosis: NINCDS ADRDA
(detail)
A, E, G‡ Mehta, 1999
Schofield, 1997 WHICAP Incidence study reporting hazard ratios (HRs) 271
(73%)
1.7 y
(detail)
Head injury ascertained by interviewer
No head injury with loss of consciousness: 88%
Head injury, latency < 10 years:         
Head injury, latency ≥ 10 years:         
Head injury, latency < 30 years:         
Head injury, latency ≥ 30 years:         
(detail)

34
-
-
-
-
Total: 34

1.00
4.50
3.00
5.40
1.70

Ref.
1.00-21.00
0.70-14.20
1.50-19.50
0.20-14.40

Ref.
0.05
0.15
0.01
0.63
*

 
 
 
 
 

 

 

 
Caucasian, Hispanic, African-American (Black)
75 (7)
(60 - )
Screening: CDR

AD Diagnosis: NINCDS ADRDA
(detail)
A, E, G‡
(detail)
Schofield, 1997
* Derived value.
‡ Covariates: "A" (age), "E" (education), "G" (gender)