Midlife cholesterol levels predict Alzheimer disease with ASCVD
Cardiovascular risk factors and glucose tolerance in midlife and risk of cognitive disorders in old age Up to a 49-year follow-up of the Helsinki Businessmen Study
Primarily neurodegenerative as well as vascular processes contribute to dementia [1-3]. Most common diagnosis for progressing dementia is probable Alzheimer disease (AD). Long-term studies have strongly promoted the idea of AD as vascular state and consequently, sporadic late-onset AD is now considered a potentially preventable condition [4,5].
It is suggested that AD can be predicted by risk factors of atherosclerotic cardiovascular disease (ASCVD). Moreover, late-onset dementia, including AD, have been related to risk factors in midlife, such as high blood pressure (BP), hypercholesterolemia, obesity, physical inactivity, smoking, stroke and diabetes [1,6,7].
However, mixed results have been published regarding potential predictors, probably due to clinical variability of dementia in old age. This heterogeneity was reduced in the Helsinki Businessmen Study (HBS), by using a Finnish, initially healthy, same gender (men, Caucasian) and socioeconomically (highest strata) similar cohort (n=3309 used in the analyses), in which all were born between 1919-1934. The HBS study started in 1964 and investigated the relationship between ASCVD risk and glucose tolerance in midlife and dementia in old age over a period of 49 years in which 1911 deaths occurred.
Dementia types were well distinguished and patients were categorized into the following groups: ‘Pure AD’ (diagnosis of AD without any hint of ASCVD, n=93), AD-ASCVD (diagnosis of AD specified either as a cause of death or in the narrative, with any concomitant ASCVD, n=126), VD (diagnosis of vascular dementia [VD] specified as a cause of death or in the narrative, n=82), dementia or memory disorder mentioned in the death certificate but not as a specific diagnosis (n=27), Lewy body disease (LBD) with or without sign of other types of dementia (n=14), other specific diagnosis for dementia or memory disorder (n=8). Only the 3 largest groups were used for further analyses.
- AD-ASCVD patients had significantly higher cholesterol at baseline.
- APOE Ɛ4 allele was present in 31.5% of a subcohort of men without dementia and 42.9, 51.4 and 45.5% in a subcohort of patients with pure AD, AD-ASCVD and VD, respectively (P=0.06).
- In this same subcohort, the mini-mental state examination (MMSE) scores were 28.5, 26.2. 27.4 and 25.8 among old-age survivors, pure AD, AD-ASCVD and VD groups, respectively (P<0.001).
- Pure AD men had the highest use of AD drugs (71%). VD patients had highest use of hypertension and diabetes drugs, which moreover, was lower in pure AD than in men without dementia.
- Smoking, BMI, systolic BP and cholesterol levels at baseline were not associated with pure AD or VD, but risk of AD-ASCVD was significantly predicted by midlife cholesterol levels in which high cholesterol (≥6.5 mmol/L) increased the risk by 67% as compared to low levels. HR per standard deviation was 1.24 (95% CI 1.04-1.47).
- One-hour glucose (adjusted for age and smoking) significantly predicted mortality without dementia but not with any type of dementia.
In this study with a long-term follow-up, pure AD (without ASCVD) was not associated with cholesterol levels, blood pressure, glucose tolerance of diabetes, whereas AD with ASCVD was significantly associated with midlife cholesterol levels.