Table 1.
Longitudinal observational studies relating lipid levels to the risk of dementia
| Study | Cohort | Population size/follow-up time | Diagnostic criteria |
Findings |
|---|---|---|---|---|
| Kuusisto et al.100 | Kuopio | n = 980 (46 AD) | DSM-IIIR | Low total cholesterol levels associated with increased AD risk |
| Age range: 66–75 years | ||||
| Follow-up: 3.5 years | ||||
| Notkola et al.30 | Seven Countries Study (Finland) | n = 444 men (47 dementia, 27 AD) | DSM-IIIR | High total cholesterol levels associated with increased AD risk |
| Baseline age: 40–59 years | ||||
| Follow-up: 15–25 years | ||||
| Moroney et al.101 | WHICAP | n = 987 (126 AD) | NINCDS-ADRDA | Low total cholesterol levels associated with increased AD risk |
| Mean age: 73 years | ||||
| Follow-up: 2.5 years | ||||
| Romas et al.26 | WHICAP | N = 1,449 | NINCDS-ADRDA | No association |
| Age: 75.8 ± 6.4 years | ||||
| Cross-sectional study | ||||
| Kalmijn et al.102 | HAAS | n = 3,734 men (251 dementia, 82 AD, 73 VaD) | DSM-IIIR, NINCDS-ADRDA | Triglyceride levels positively associated with AD risk |
| Mean baseline age: 53 years | ||||
| Mean follow-up: 25 years | ||||
| Kivipelto et al.103 | CAIDE Study | n = 1,449 (57 dementia, 48 AD) | DSM-IV, NINCDS-ADRDA | Midlife high total cholesterol levels associated with increased AD risk |
| Mean baseline age: 50 years | ||||
| Mean follow-up: 21 years | ||||
| Tan et al.27 | Framingham Study | n =1,026 subjects who had undergone biennial evaluation for cardiovascular risk factors since 1950 and who were alive and free of stroke and dementia at examination cycle 20 (1988–1989); 77 developed AD afterwards | DSM-IV, NINCDS-ADRDA | No association |
| Reitz et al.104 | WHICAP | n = 1,168 (119 AD, 54 VaD) | DSM-IIIR, NINCDS-ADRDA | Higher total cholesterol levels associated with decreased AD risk. Higher LDL cholesterol and non-HDL-cholesterol levels associated with increased VaD risk |
| Mean age: 78.4 years | ||||
| Follow-up: 4.8 years | ||||
| Dufouil et al.90 | Three-City Study | n = 9,294 | DSM-IV, NINCDS-ADRDA | Hyperlipidemia associated with increased risk of non-AD dementia, lipid-lowering treatment associated with decreased dementia risk |
| Age: 74.2 ± 5.5 years | ||||
| Cross-sectional analyses | ||||
| Whitmer et al.31 | Kaiser Permanente Medical Care Program of Northern California | n = 8,845 (721 dementia) | ICD-9-CM | Positive association |
| Baseline age: 40–44 years | ||||
| Mean follow-up: 27 years | ||||
| Li et al.24 | ACT Study | n = 2,141 (152 AD) | DSM-IV, NINCDS-ADRDA | No association |
| Mean age: 74.9 years | ||||
| Follow-up: 5.6 years | ||||
| Mainous et al.25 | NHEFS | n = 6,558 | ICD-9 | No association |
| Baseline age: 40–74 years | ||||
| Follow-up: 20 years | ||||
| Mielke et al.105 | Göteborg | n = 382 (93 dementia) | DSM-IIIR, NINCDS-ADRDA | High total cholesterol levels associated with reduced risk of dementia |
| Baseline age: 70 years | ||||
| Follow-up: 18 years | ||||
| Kivipelto et al.29 | CAIDE Study | n = 1,449 (61 dementia, 48 AD) | DSM-IV, NINCDS-ADRDA | Midlife high total cholesterol levels associated with increased AD risk |
| Mean baseline age: 50 years | ||||
| Mean follow-up: 21 years | ||||
| Hayden et al.106 | Cache County Study | n = 3,264 (185 dementia) | DSM-IIIR, NINCDS-ADRDA | High total cholesterol levels associated with increased AD risk |
| Mean age: 73.7 years | ||||
| Follow-up: 3.2 years | ||||
| Stewart et al.32 | HAAS | 1,027 Japanese American men (56 AD) | DSM-IIIR, NINCDS-ADRDA | Decline in cholesterol levels in men at least 15 years before diagnosis of dementia |
| Mean age: 80.2 years | ||||
| Follow-up: 26 years | ||||
| Solomon et al.107 | Kaiser Permanente Northern California Medical Group | N = 9,844 | ICD-9 | Midlife serum total cholesterol levels associated with increased risk of AD and VaD |
| Age at study entry: 40–45 years | ||||
| Follow-up: 3 decades | ||||
| Reitz et al.108 | WHICAP | n = 1,130 (101 AD) | DSM-IIIR, NINCDS-ADRDA | High HDL levels associated with reduced AD risk |
| Mean age: 75.7 years | ||||
| Follow-up: 4 years | ||||
| Beydoun et al.33 | BLSA | n = 1,604 (259 dementia, 182 AD) | DSM-IIIR, NINCDS-ADRDA | Decline in total cholesterol levels associated with increased dementia risk |
| Mean age: 57.6 years | ||||
| Follow-up: 25 years | ||||
| Solfrizzi et al.109 | ILSA | n = 2,097 | DSM-IIIR, NINCDS-ADRDA | Metabolic syndrome associated with higher risk of VaD |
| Age: 72.9 ± 5.6 years | ||||
| Follow-up: 3.5 years | ||||
| Reynolds et al.110 | Swedish Adoption Twin Study of Aging | N = 819 twins | DSM-IV, NINCDS-ADRDA | In women but not men, higher HDL cholesterol and lower triglyceride levels predict better maintenance of cognitive abilities |
| Age: 50–96 years | ||||
| Follow-up: 16 years | ||||
| Mielke et al.28 | Prospective Population Study of Women | N = 1,462 women without dementia | DSM-IIIR, NINCDS-ADRDA | Midlife cholesterol level is not associated with increased risk of AD |
| Age: 38–60 years | ||||
| Follow-up: 32 years |
AD Alzheimer's disease, BLSA Baltimore Longitudinal Study of Aging, DSM-IIIR Diagnostic and Statistical Manual of Mental Disorders, third edition, text revision, DSM-IV Diagnostic and Statistical Manual of Mental Disorders fourth edition, HAAS Honolulu-Asia Aging Study, ICD-9 International Classification of Diseases, ICD-9-CM International Classification of Diseases, ninth revision, clinical modification, ILSA Italian Longitudinal Study on Ageing, NHEFS National Health and Nutrition Examination Survey I Epidemiologic Follow-up Study NINCDS-ADRDA National Institute of Neurological and Communicative Disorders and Stroke—Alzheimer's Disease and Related Disorders Association, VaD vascular disease, WHICAP Washington Heights–Inwood Columbia Aging Project