Table 2.

Direct association between modifiable factors and cognitive trajectory subgroups, with reference to average performers *(N = 6,432).

	Highest performers		Lowest performer
	(n = 2,298)		(n = 642)
	Relative RR (95% CI)	P-value	Relative RR (95% CI)	P-value
Social/lifestyle factors
Education> 12 years	4.63 (4.07–5.29)	<0.001	0.71 (0.59–0.85)	<0.001
Living alone at home	0.89 (0.77–1.02)	0.09	1.26 (1.04–1.52)	0.02
Ever smoker	0.90 (0.79–1.03)	0.12	0.92 (0.76–1.11)	0.41
Ever alcohol intake	1.39 (1.17–1.66)	<0.001	0.79 (0.63–0.99)	0.04
Chronic conditions
Hypertension	0.69 (0.60–0.80)	<0.001	0.89 (0.72–1.10)	0.28
Dyslipidemia	1.06 (0.93–1.22)	0.36	1.30 (1.07–1.57)	0.007
Obesity	0.84 (0.73–0.97)	0.01	0.89 (0.73–1.09)	0.26
Diabetes	0.69 (0.56–0.86)	0.001	1.27 (0.98–1.64)	0.07
Pre-frailty/frailty	0.60 (0.52–0.68)	<0.001	1.77 (1.47–2.14)	<0.001
Depression	0.68 (0.54–0.85)	0.001	1.23 (0.94–1.60)	0.13
Chronic kidney disease	0.87 (0.75–1.01)	0.06	1.00 (0.83–1.21)	0.99

RR, risk ratio. * Compared to average performers (n = 3,492), and additionally adjusted for age, gender and ethnicity. (1) hypertension was defined as on treatment for high BP or BP > 140/90 mmHg at study entry; (2) dyslipidemia was defined as those taking cholesterol-lowering medications or serum cholesterol ≥212 mg/dL (≥5 mmol/L; Australia) and ≥240 mg/dL (≥6.2 mmol/L; U.S.) or LDL > 160 mg/dL (>4.1 mmol/L); (3) obesity was defined as body mass index ≥30; (4) diabetes was defined from self-report or fasting glucose ≥126 mg/dL (≥7 mmol/L) or on treatment for diabetes; (5) frailty was defined using the adapted Fried frailty criteria, including being underweight, weak grip strength, exhaustion, slow walking speed and low physical activity, with pre-frail including anyone with 1 or 2 criteria and Frail as anyone with three or more criteria (22); (6) depression was defined as CES-D-10 ≥8; (7) chronic kidney disease was defined as eGFR < 60 ml/min/1.73 m2 or urinary albumin to creatinine ratio ≥3 mg/mmol.