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

Figures & data

Figure 1. Flow chart of the procedures in the Helsinki Businessmen study 1964–2014. ApoE: apolipoprotein E; MMSE: Mini-Mental State Examination; ASCVD: atherosclerotic cardiovascular disease.

Table 1. Study groups and types of dementia in the Helsinki businessmen study follow-up.

Group^a	No.	Proportion ofdementia	Year of diagnosis or death, median (IQR)	Age (survivors by31 December 2013,non-survivors at dementia diagnosis or death), median (IQR)
Survivors through 31 December 2013	1124	–	–	86 (83–89)
Alzheimer disease without ASCVD(“pure” AD)	93	25.5	2001 (1998–2003)	75 (72–80)
Alzheimer disease with ASCVD	126	34.5	2004 (2001–2006)	78 (76–83)
Vascular dementia	82	22.5	1998 (1993–2002)	74 (70–77)
Undefined dementia or cognitive disorder without specific diagnosis	27	7,4	2000 (1991–2003)	75 (69–81)
Dementia due to Parkinson’s disease	15	4.1	1999 (1997–2006)	75 (69–81)
Lewy body disease	14	3.8	2000 (1998–2002)	76 (73–78)
Other defined diagnosis (1 brain lymphoma, 1 glioma, 1 neuroborreliosis, 1 frontotemporal degeneration, 1 Creutzfeldt-Jacob disease, 3 alcohol-related dementia)	8	2.2	2000 (1997–2004)	70 (65–76)
Death without cognitive disorders	1820	–	1999 (1990–2006)	74 (65–81)

IQR: interquartile range.

^a Vital status was verified and death certificates retrieved from the Cause-of-Death Registry of Statistics Finland of men who had died through 31 December 2013. Dementia type and presence of atherosclerotic cardiovascular disease (ASCVD) was assessed using diagnoses and narratives in death certificates.

Table 2. Midlife characteristics of the study cohort according to later dementia type and survival status.

Variable in midlife(in 1964–1973), age-adjusted	Survivors by31 December 2013,n = 1124	Any dementia,n = 365	Dementia typeAD without ASCVD(“pure” AD), n = 93	AD with ASCVD,n = 126	VD, n = 82	Dead by31 December 2013without knowndementia, n= 1820
Age at 1st visit, year, median (IQR)	40 (37–43)	43 (40–46)	42 (40–46)	43 (41–46)	44 (40–47)	42 (39–46)
Body mass index, kg/m^2, mean (SE)	25.4 (0.08)	25.7 (0.3)	25.5 (0.3)	26.0 (0.3)	25.9 (0.3)	26.2 (0.07)^a
Blood pressure, mmHg mean (SE)
Systolic	132.9 (0.4)	133.0 (1.4)	133.2 (1.7)	134.4 (1.4)	135.0 (1.8)	138.1 (0.4)^a
Diastolic	84.6 (0.3)	84.7 (0.9)	84.5 (1.1)	85.3 (0.9)	86.5 (1.2)	87.8 (0.2)^a
One-hour glucose^b, mmol/L, mean (SE)	6.1 (0.06)	6.5 (0.2)	5.9 (0.2)	6.4 (0.2)	6.6 (0.2)	6.5 (0.05)^a
Cholesterol, mmol/L, mean (SE)	6.4 (0.03)	6.7 (0.1)	6.4 (0.1)	6.8 (0.1)^a	6.7 (0.1)^a	6.7 (0.03)^a
Triglycerides^c, mmol/L, mean (SE)	1.48 (0.03)	1.80 (0.12)	1.33 (0.14)	1.69 (0.11)	2.15 (0.15)^a	1.59 (0.03)
Ever smoker, n (%)	591 (52.6)	222 (60.8)	57 (61.3)^a	74 (58.7)	50 (61.0)^a	1151 (63.2)^a

ASCVD: atherosclerotic cardiovascular disease; AD: Alzheimer disease; IQR: interquartile range; SE: standard error; VD: vascular dementia.

^a Significant versus survivors.

^b Measured in 2034 men at baseline.

^c Measured in 1020 men at baseline.

Table 3. Proportion of drug reimbursement in study groups.

		Type of incident dementia duringfollow-up
Diagnosis for drugreimbursement through 2007	Survivors to old age without diagnosed dementia^a, n = 1124	AD without ASCVD(pure AD), N = 93	AD with ASCVD,n = 126	VD, n = 82	p value betweengroups
AD	2.4	71.0	64.3	7.3	<.001
Diabetes	8.4	5.4	11.1	23.2	<.001
Hypertension	31.0	28.3	33.3	42.9	.18

ASCVD: atherosclerotic cardiovascular disease; AD: Alzheimer disease; VD: vascular dementia.

^a Vital status verified from national registers through 31 December 2013 when median age was 86 years.

^bSignificant versus hypercontrols.

Table 4. Risk of incident dementia and death without diagnosed dementia during follow-up according to midlife risk factors.

		Type of dementia
Risk factor at baseline^a	Any dementia, n = 365	AD without ASCVD(pure AD),n = 93HR (95% CI)^b	AD with ASCVD, n = 126	VD, n = 82	AD-with ASCVD plus VD, n = 208	Deaths by31 December 2013 without diagnosed dementia, n = 1820
Age, year	1.14 (1.11–1.16)	1.13 (1.08–1.19)	1.16 (1.11–1.20)	1.14 (1.08–1.20)	1.15 (1.11–1.19)	1.09 (1.08–1.10)
Ever smoking, yes/no	1.13 (0.91–1.39)	1.20 (0.78–1.86)	1.03 (0.72–1.48)	1.42 (0.89–2.27)	1.16 (0.88–1.55)	1.25 (1.13–1.37)
BMI, kg/m^2, per SD	1.04 (0.93–1.17)	0.90 (0.73–1.17)	1.13 (0.93–1.37)	1.05 (0.83–1.34)	1.10 (0.95–1.28)	1.12 (1.07–1.17)
BMI, </≥ 30 kg/m^2	1.07 (0.70–1.62)	0.54 (0.17–1.71)	1.35 (0.70–2.60)	1.17 (0.50–2.71)	1.27 (0.76–2.14)	1.43 (1.24–1.66)
Systolic BP, mm Hg, per SD	0.96 (0.85–1.08)	0.94 (0.73–1.21)	1.00 (0.81–1.22)	0.97 (0.75–1.25)	0.98 (0.84–1.15)	1.18 (1.13–1.23)
Systolic BP, </≥ 160 mm Hg	1.09 (0.75–1.58)	0.75 (0.30–1.86)	1.39 (0.77–2.49)	1.02 (0.46–2,23)	1.23 (0.77–1.96)	1.58 (1.38–1.80)
Cholesterol, mmol/L, per SD	1.12 (1.01–1.24)	0.95 (0.76–1.18)	1.24 (1.04–1.47)	1.20 (0.96–1.49)	1.22 (1.07–1.40)	1.11 (1.06–1.16)
Cholesterol, </≥ 6.5 mmol/L	1.19 (0.96–1.47)	0.75 (0.49–1.14)	1.67 (1.16–2.40)	1.26 (0.81–1.97)	1.49 (1.13–1.98)	1.18 (1.08–1.28)
Glucose adjusted for age and smoking
1-h glucose, per SD	1.08 (0.97–1.21)	0.83 (0.64–1.09)	1.11 (0.92–1.34)	1.22 (0.98–1.51)	1.15 (1.00–1.33)	1.13 (1.08–1.18)
1-h glucose, ≤/>9.0 mmol/L	1.00 (0.65–1.54)	0.17 (0.02–1.24)	1.35 (0.70–2.59)	1.45 (0.66–3.17)	1.39 (0.84–2.30)	1.39 (1.19–1.61)

ASCVD: atherosclerotic cardiovascular disease; AD: Alzheimer disease; BMI: body mass index; BP: blood pressure; CI: confidence interval; HR: hazard ratio; SD: standard deviation; VD: vascular dementia.

^a All factors (either continuous or dichotomous) simultaneously in the model.

^b Hazard ratio with 95% confidence interval was calculated using the Cox proportional hazards model. For deaths without dementia the reference group was surviving men without known dementia. For all dementia and each dementia type, the reference group was men without diagnosed dementia (dead or surviving by 31 December 2013). For specific dementia types, men with other dementia types were excluded in the analysis.