The relationship between cholesterol and cognitive function is homocysteine-dependent

Figures & data

Table 1 Demographic characteristics of the study population (N=1,889)

Participant characteristics	Mean or N	SD or %
Age (years)	73.45	5.93
Female (%)	1,017	53.9
Years of education	2.39	3.00
Body mass index (kg/m^2)	23.08	3.77
Systolic blood pressure	152.21	27.87
Diastolic blood pressure	86.18	12.83
Consume alcohol (%)	725	38.4
Smoker (%)	750	39.7
APOEe4 carriers	299	15.9
History of (%)
Parkinson’s	10	0.5
Diabetes	78	4.1
Hypertension	1,316	69.7
Stroke	72	3.8
Heart disease	277	14.7
Arthritis	223	11.8
Thyroid disease	12	0.6
Kidney disease	34	1.8
Liver disease	19	1.0
Cancer	21	1.1
Head injury	71	3.8
Fracture	167	8.9

Abbreviations: N, number of participants; SD, standard deviation.

Table 2 Summary of cognitive functions measured in the study population (N=1,889)

Cognitive functions	Summary measures
	Mean	SD	Min	Median	Max
CSID test	25.84	3.54	6.00	27.00	30.00
IU Story Recall test	5.06	3.13	0.00	5.00	14.00
Animal Fluency test	13.36	4.93	0.00	13.00	32.00
CERAD Word Listing Learning test	13.24	4.46	0.00	13.00	29.00
CERAD Word Listing Recall test	4.45	2.30	0.00	5.00	10.00
IU Token test	16.66	5.26	0.00	18.00	24.00
Boston Naming test	13.73	3.54	0.00	14.00	20.00
Stick Design test	10.40	2.54	0.00	12.00	12.00
Delayed Stick Design test	5.01	2.69	0.00	5.00	12.00

Abbreviations: N, number of participants; SD, standard deviation; Min, minimum; Max, maximum; CSID, Community Screening Instrument for Dementia; IU, Indiana University; CERAD, the Consortium to Establish a Registry for Alzheimer’s Disease.

Table 3 Summary of biomarker measures (N=1,889)

Biomarker	Mean	SD	Median	Interquartile range
Total cholesterol level (mg/dL)	158.9	47.1	154.3	(125.3, 186.7)
HDL (mg/dL)	49.3	17.7	46.0	(37.1, 58)
LDL (mg/dL)	91.1	35.2	88.9	(65.0, 112.1)
Triglycerides (mg/dL)	40.6	32.1	32.9	(22.8, 48.3)
Homocysteine (μmol/L)	17.2	8.4	15.3	(11.8, 20.1)
Glucose (mg/dL)	85.9	30.3	79.3	(69.7, 92.1)
Cholesterol quartile groups
Q1 (≤125.26 mg/dL)	104.3	16.0	106.7
Q2 (125.26, 154.25 mg/dL)	140.1	8.4	139.6
Q3 (154.25, 186.73 mg/dL)	170.0	9.5	170.1
Q4 (>186.73 mg/dL)	222.4	30.4	214.9
Homocysteine quartile groups
Q1 (≤11.81 μmol/L)	9.4	1.9	9.8
Q2 (11.81, 15.25 μmol/L)	13.5	0.9	13.4
Q3 (15.25, 20.12 μmol/L)	17.5	1.4	17.4
Q4 (>20.12 μmol/L)	28.5	8.5	25.9

Abbreviations: N, number of participants; SD, standard deviation; HDL, high-density lipoprotein; LDL, low-density lipoprotein; Q, quartile group.

Table 4 Results of ANCOVA models with composite cognitive scores as the outcome variable, cholesterol Qs as independent variables stratified by homocysteinea

Homocysteine	Cholesterol	Total cohort (N=1,889)			Sub-sample (N=1,700)b
		Estimation	SE	P-value	Estimation	SE	P-value
Q1 (≤11.81 μmol/L)	Q1 (≤125.26 mg/dL)	−0.18	0.08	0.0208*	−0.19	0.07	0.0063*
	Q2 (125.26, 154.25 mg/dL)	−0.08	0.08	0.3078	−0.03	0.07	0.6506
	Q3 (154.25, 186.73 mg/dL)	0.20	0.08	0.0146*	0.15	0.07	0.0342
	Q4 (>186.73 mg/dL)	Reference	–	–	Reference	–	–
Q2 (11.81, 15.25 μmol/L)	Q1 (≤125.26 mg/dL)	−0.16	0.08	0.0355*	−0.10	0.07	0.1342
	Q2 (125.26, 154.25 mg/dL)	−0.15	0.08	0.0506	−0.07	0.07	0.2960
	Q3 (154.25, 186.73 mg/dL)	0.01	0.08	0.8820	0.06	0.07	0.3653
	Q4 (>186.73 mg/dL)	Reference	–	–	Reference	–	–
Q3 (15.25, 20.12 μmol/L)	Q1 (≤125.26 mg/dL)	−0.22	0.08	0.0063*	−0.23	0.07	0.0017*
	Q2 (125.26, 154.25 mg/dL)	−0.06	0.07	0.4055	−0.13	0.07	0.0490
	Q3 (154.25, 186.73 mg/dL)	0.00	0.07	0.9613	−0.05	0.07	0.4076
	Q4 (>186.73 mg/dL)	Reference	–	–	Reference	–	–
Q4 (>20.12 μmol/L)	Q1 (≤125.26 mg/dL)	−0.06	0.08	0.4372	−0.05	0.07	0.4335
	Q2 (125.26, 154.25 mg/dL)	0.06	0.09	0.5061	0.00	0.07	0.9747
	Q3 (154.25, 186.73 mg/dL)	−0.05	0.08	0.5209	−0.02	0.06	0.7252
	Q4 (>186.73 mg/dL)	Reference	–	–	Reference	–	–
Normal homocysteine (≤14 μmol/L)	Q1 (≤125.26 mg/dL)	−0.17	0.06	0.0050	−0.14	0.05	0.0103
	Q2 (125.26, 154.25 mg/dL)	−0.09	0.06	0.1219	−0.02	0.05	0.6965
	Q3 (154.25, 186.73 mg/dL)	0.12	0.06	0.0411	0.12	0.05	0.0220
	Q4 (>186.73 mg/dL)	Reference	–	–	Reference	–	–

Notes:

a All models were adjusted for age, sex, years of education, smoking status, body mass index, and history of heart disease.

b Excluding participants in the bottom 10% of composite cognitive scores.

* Statistically significant values.

Abbreviations: ANCOVA, analysis of covariance; N, number of participants; Q, quartile group; SE, standard error.

Figure 1 Predicted mean composite cognitive scores by homocysteine and cholesterol quartile groups.

Notes: Homocysteine quartile groups are divided into Q1 (≤11.81 μmol/L); Q2 (11.81, 15.25 μmol/L); Q3 (15.25, 20.12 μmol/L); Q4 (>20.12 μmol/L). Cholesterol quartile groups are divided into Q1 (≤125.26 mg/dL); Q2 (125.26, 154.25 mg/dL); Q3 (154.25, 186.73 mg/dL); Q4 (>186.73 mg/dL).