Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6...

64
Supplemental Data {2 Column Table} Table S1. Studies of inflammation and cognitive function in type 2 diabetes Study Sample Design Numbe r Basel ine mean age Measurem ent of inflamma tion Cognitive measures Adjustmen t variables Association with cognitive function Chen et al. [9] (2011 ) Patients with type 2 diabetes ; China Cross- sectiona l, observat ional 101 Mean 63 ± 8 years CRP MCI identified on the basis of cognitive screening None Higher CRP in group with MCI compared with group free of MCI.

Transcript of Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6...

Page 1: Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6 associated with lower cognitive function and steeper estimated lifetime decline (fully adjusted

Supplemental Data

{2 Column Table}

Table S1. Studies of inflammation and cognitive function in type 2 diabetes

Study Sample Design Num-

ber

Base-

line

mean

age

Measure-

ment of in-

flammation

Cognitive mea-

sures

Adjustment

variables

Association with

cognitive function

Chen et

al. [9]

(2011)

Patients with

type 2 dia-

betes;

China

Cross-sec-

tional, obser-

vational

101 Mean

63 ± 8

years

CRP MCI identified

on the basis of

cognitive

screening in-

strument

None Higher CRP in

group with MCI

compared with

group free of MCI.

Keller et

al. [45]

(2012)

Patients with

type 2 dia-

betes partici-

pating in the

4-year

prospective,

observa-

1,066 Mean

68 ± 4

years

Plasma fib-

rinogen at

baseline

Composite

score from

seven cognitive

Age and sex Higher baseline

fibrinogen associ-

ated with steeper

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Edinburgh

Type 2 Dia-

betes Study;

Scotland

tional tests cognitive decline

Keller et

al. [46]

(2012)

Patients with

type 2 dia-

betes partici-

pating in the

Edinburgh

Type 2 Dia-

betes Study;

Scotland

4-year

prospective,

observa-

tional

1,066 Mean

68 ± 4

years

Plasma IL-6

at baseline

Composite

score from

seven cognitive

tests

Age and sex Higher baseline

IL-6 associated

with steeper cogni-

tive decline.

Marioni

et al.

[43]

(2011)

Patients with

type 2 dia-

betes partici-

pating in the

Edinburgh

Cross-sec-

tional, obser-

vational

1,066 Mean

68 ± 4

years

Plasma fib-

rinogen

Composite

score from

seven cognitive

tests

Age and sex Higher fibrinogen

associated with

lower cognitive

function.

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Type 2 Dia-

betes Study;

Scotland

Marioni

et al.

[44]

(2010)

Patients with

type 2 dia-

betes partici-

pating in the

Edinburgh

Type 2 Dia-

betes Study;

Scotland

Cross-sec-

tional, obser-

vational

1,066 Mean

68 ± 4

years

Plasma IL-6,

TNF-α, and

CRP

Composite

score from

seven cognitive

tests and esti-

mate of pre-

morbid ability

Age, sex,

education,

cardiovascu-

lar disease,

duration of

diabetes,

HbA1c, and

estimated pre-

morbid ability

Higher IL-6 asso-

ciated with lower

cognitive function

and steeper esti-

mated lifetime

decline (fully ad-

justed analyses).

Association of

higher TNF-α with

lower cognitive

function and esti-

mated lifetime

decline only in

analyses adjusted

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for age, sex, and

estimated pre-mor-

bid ability. No

consistent finding

for CRP.

Umegak

i et al.

[16]

(2014)

Patients with

type 2 dia-

betes;

Japan

6-year

prospective,

observa-

tional

79 Mean

74 ± 5

years

Mean of

CRP mea-

sured at

baseline and

annual fol-

low-ups

Composite

score from

MMSE, Digit

Symbol Cod-

ing, Stroop,

and word re-

call. Analyses

of ‘decliners’

versus ‘non-de-

cliners’ on

bases of com-

posite score

None No association.

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and individual

cognitive tests.

CRP, C-reactive protein; IL-6, interleukin-6; MCI, mild cognitive impairment; MMSE, Mini-Mental State Examination; TNF-α, tu-

mor necrosis factor-alpha.

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{2 Column Table}

Table S2. Studies of microvascular disease and cognitive function in type 2 diabetes

Study Sample Design Num-

ber

Base-

line

mean

age

Measurement of

microvascular

disease

Cognitive

measures

Adjustment

variables

Association

with cogni-

tive function

de Bresser et

al. [49]

(2010)

Patients with

type 2 diabetes

participating in

the Utrecht

Diabetic En-

cephalopathy

Study;

The Nether-

lands

4-year

prospective,

observa-

tional

122 Mean

66 ± 6

years

Ophthalmolo-

gist-identified

presence versus

absence of

retinopathy ac-

cording to ‘stan-

dard clinical

practice’ at

baseline

Composite

score from

11 cognitive

tests, esti-

mate of pre-

morbid abil-

ity, total

brain vol-

ume, lateral

ventricular

volume,

Age, sex,

and pre-

morbid abil-

ity for

analyses of

cognitive

function.

Age and sex

for analyses

of imaging

No associa-

tion.

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white matter

hyperinten-

sity volumes,

and cerebral

infarcts

data.

de Galan

et al. [35]

(2009)

Patients with

type 2 diabetes

participating in

ADVANCE

arm on

glycemic con-

trol, receiving

standard target

versus target

HbA1c ≤6.5%;

Australia

5-year trial

on effects of

intensified

blood pres-

sure control

and intensi-

fied

glycemic

control

11,140 Mean

66 ± 6

years

‘Major diabetic

eye disease’

At baseline

and 2-year

intervals:

MMSE fol-

lowed by

clinical inter-

view for pa-

tients with

MMSE <24

or suspected

dementia.

‘Normal’

None Cross-sec-

tional analy-

sis: in-

creased

prevalence

of major

diabetic eye

disease in

groups with

cognitive

dysfunction.

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cognitive

function de-

fined as

MMSE ≥28;

‘mild dys-

function’ as

MMSE = 24-

27; ‘severe

dysfunction’

as MMSE

<24. Addi-

tional use of

MMSE as

continuous

measure.

Hugen-

schmidt et al.

Patients with

type 2 diabetes

40-month

prospective,

1,862 Mean

62 ± 6

Presence of no

retinopathy, of

Digit Symbol

Coding (pri-

Age, sex,

ethnicity,

Cross-sec-

tional asso-

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[50] (2014) participating in

ACCORD-Eye

and AC-

CORD-MIND

substudies of

ACCORD;

North America

observa-

tional

years mild non-prolif-

erative retinopa-

thy, or of mod-

erate/severe

retinopathy at

baseline; based

on ETDRS chart

mary out-

come),

MMSE, Rey

Auditory

Verbal

Learning,

and Stroop

(secondary

outcomes) at

baseline and

20 and 40

months. To-

tal brain vol-

ume, white

matter vol-

ume, gray

matter vol-

education,

smoking,

geographic

region, du-

ration of

diabetes,

HbA1c,

cholesterol,

triglyc-

erides,

blood pres-

sure, anti-

hyperten-

sive medi-

cation use,

depression,

alcohol, and

ciation of

retinopathy

with lower

gray matter

volume but

not with

cognitive

function.

Prospective

association

of retinopa-

thy with

steeper 40-

month (but

not 20-

month) de-

cline on

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ume, and

abnormal

white matter

volume at

baseline and

40 months.

neuropathy.

Additional

adjustment

for visual

acuity for

analyses of

cognitive

function and

for total

intracranial

volume for

analyses of

brain vol-

umes.

MMSE and

Digit Sym-

bol Coding.

Statistically

non-signifi-

cant trend

for associa-

tion of base-

line

retinopathy

with greater

increase in

white matter

abnormali-

ties during

40-month

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follow-up.

Manschot et

al. [25]

(2007)

Patients with

type 2 diabetes

participating in

the Utrecht

Diabetic En-

cephalopathy

Study;

The Nether-

lands

Cross-sec-

tional, ob-

servational

122 Mean

66 ± 6

years

Presence versus

absence of

retinopathy

based on scores

on diabetic

retinopathy

severity scale

(Wisconsin Epi-

demiologic

Study of Dia-

betic Retinopa-

thy) at baseline

Composite

score from

11 cognitive

tests, esti-

mate of pre-

morbid abil-

ity, cortical

atrophy, and

white matter

lesions

Age, sex,

and esti-

mated pre-

morbid abil-

ity

No associa-

tion of

retinopathy

with esti-

mated life-

time decline

in cognitive

function.

Association

of retinopa-

thy with

presence of

cortical atro-

phy (analy-

sis addition-

ally control-

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ling for

lipid-lower-

ing drugs

and cerebral

infarcts).

ACCORD, Action to Control Cardiovascular Risk in Diabetes; ACCORD-MIND, Action to Control Cardiovascular Risk in Diabetes-

Memory in Diabetes; ADVANCE, Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled

Evaluation; ETDRS, Early Treatment of Diabetic Retinopathy Study; MMSE, Mini-Mental State Examination.

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{2 Column Table}

Table S3. Studies of markers of macrovascular disease and cognitive function in type 2 diabetes

Study Sample Design Num-

ber

Base-

line

mean

age

Macrovascular

disease

Cognitive mea-

sures

Adjust-

ment vari-

ables

Association

with cogni-

tive function

Bruce et

al. [14]

(2008)

Patients with

type 2 dia-

betes partici-

pating in the

Fremantle

Diabetes

Study; Aus-

tralia

8-year ret-

rospective,

observa-

tional

302 Mean

76 ± 5

years

‘Cerebrovascular

disease’ (stroke

and TIA), ‘CHD’

(MI, angina, coro-

nary artery bypass,

and evidence of

MI on ECG), and

peripheral arterial

disease at baseline

and 8 years earlier

Dementia and

MCI identified

from screening

instruments/clini-

cal interview

None Cross-sec-

tional analy-

ses: increased

prevalence of

cerebrovascu-

lar disease

across cogni-

tive groups,

with highest

prevalence in

dementia

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group, fol-

lowed by

MCI group

and unim-

paired group.

Increased

prevalence of

PAD in group

with any cog-

nitive impair-

ment (in

model con-

trolling for

sex, duration

of diabetes,

and stroke)

and in group

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with dementia

(in model

controlling

for age, sex,

and duration

of diabetes).

Prospective

analyses:

cerebrovascu-

lar disease

(unadjusted

analysis) and

PAD (model

controlling

for age, sex,

duration of

diabetes, and

Page 16: Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6 associated with lower cognitive function and steeper estimated lifetime decline (fully adjusted

waist-hip

ratio) 8 years

earlier both

associated

with poorer

cognitive

outcome. No

findings for

CHD.

Bruce et

al. [21]

(2008)

Patients with

type 2 dia-

betes partici-

pating in the

Fremantle

Diabetes

Study; Aus-

tralia

8-year ret-

rospective,

2-year

prospective,

observa-

tional

205 Mean

75 ± 4

years

Cerebrovascular

disease and periph-

eral arterial disease

assessed 8 years

prior to baseline

cognitive assess-

ment

Dementia and

MCI identified

from screening

instruments/clini-

cal interview at

baseline and at 2-

year follow-up.

‘Cognitive de-

None No associa-

tion.

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cline’ defined as

downward con-

version between

‘normal’, MCI,

and dementia.

Chen et

al. [9]

(2011)

Patients with

type 2 dia-

betes;

China

Cross-sec-

tional, ob-

servational

101 Mean

63 ± 8

years

ABI and cIMT MCI identified

on the basis of

screening instru-

ment

None Lower ABI

and higher

cIMT in

group with

MCI com-

pared with

group free of

MCI.

Chen et

al. [11]

(2012)

Patients with

type 2 dia-

betes;

Cross-sec-

tional, ob-

servational

157 Mean

55 ± 7

years

cIMT MCI identified

on the basis of

cognitive screen-

ing instrument

None Higher cIMT

in group with

MCI com-

pared with

Page 18: Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6 associated with lower cognitive function and steeper estimated lifetime decline (fully adjusted

China group free of

MCI. Inverse

correlation

between cog-

nitive scores

and cIMT.

Cukier-

man-

Yaffe

et al. [13]

(2009)

Patients with

type 2 dia-

betes partici-

pating in AC-

CORD-

MIND;

North Amer-

ica

Cross-sec-

tional anal-

ysis of trial

on blood

pressure,

lipids, and

glycemic

control

2,977 Mean

63 ± 6

years

Stroke, ‘CVD’

(stroke, MI, angina

with ischemic

changes, and coro-

nary procedure)

Digit Symbol

Coding (primary

outcome),

MMSE, Rey Au-

ditory Verbal

Learning, and

Stroop (sec-

ondary out-

comes)

Age Association

of stroke with

lower cogni-

tive function.

Association

of CVD

(without

stroke) with

lower verbal

memory but

higher

Page 19: Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6 associated with lower cognitive function and steeper estimated lifetime decline (fully adjusted

MMSE

scores.

de Galan

et al. [35]

(2009)

Patients with

type 2 dia-

betes partici-

pating in AD-

VANCE arm

on glycemic

control; Aus-

tralia

5-year

prospective

trial on ef-

fects of

intensified

blood pres-

sure control

and intensi-

fied

glycemic

control

11,140 Mean

66 ± 6

years

Stroke, MI, major

coronary event

(non-fatal MI,

death from coro-

nary event), and

major CVD event

(MI, stroke, and

cardiovascular

death) during fol-

low-up

At baseline and

2-year intervals:

MMSE followed

by clinical inter-

view for patients

with MMSE <24

or suspected de-

mentia. ‘Normal’

cognitive func-

tion defined as

MMSE ≥28;

‘mild dysfunc-

tion’ as MMSE =

24-27; ‘severe

dysfunction’ as

Age, sex,

education,

and treat-

ment allo-

cation

Cross-sec-

tional, unad-

justed analy-

ses: associa-

tion of stroke

and major

CVD event

with lower

cognitive

function. No

finding for

MI. Prospec-

tive analyses

(adjusted):

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MMSE <24. Ad-

ditional use of

MMSE as contin-

uous measure.

baseline mild

and severe

impairment

(versus unim-

paired) asso-

ciated with

increased risk

of major

CVD event,

stroke, and

major coro-

nary event

during fol-

low-up.

Lower

MMSE at

baseline asso-

Page 21: Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6 associated with lower cognitive function and steeper estimated lifetime decline (fully adjusted

ciated with

increased risk

of major

CVD event.

Feinkohl

et al. [51]

(2013)

Patients with

type 2 dia-

betes partici-

pating in the

Edinburgh

Type 2 Dia-

betes Study;

Scotland

4-year

prospective,

observa-

tional

1,066 Mean

68 ± 4

years

MI, stroke, angina,

ABI, and cIMT at

baseline

MMSE, compos-

ite score from

seven cognitive

tests, and esti-

mate of pre-mor-

bid ability

Age, sex,

choles-

terol,

blood

pressure,

smoking,

and esti-

mated

pre-mor-

bid ability

Cross-sec-

tional analy-

ses: stroke,

angina, and

MI associated

with lower

cognitive

function.

Prospective

analyses:

stroke, higher

cIMT, and

lower ABI

Page 22: Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6 associated with lower cognitive function and steeper estimated lifetime decline (fully adjusted

associated

with in-

creased late-

life cognitive

decline and

increased

estimated

lifetime de-

cline.

Manschot

et al. [20]

(2006)

Patients with

type 2 dia-

betes partici-

pating in the

Utrecht Dia-

betic En-

cephalopathy

Cross-sec-

tional, ob-

servational

122 Mean

66 ± 6

years

‘Any macrovascu-

lar event’ defined

as MI, stroke, or

surgery/endovas-

cular treatment for

coronary, carotid

or peripheral arte-

Composite scores

on five cognitive

domains from 11

cognitive tests,

estimate of pre-

morbid ability,

cortical atrophy,

and white matter

Age, sex,

and esti-

mated

pre-mor-

bid ability

Association

of infarcts

with steeper

estimated

lifetime de-

cline in pro-

cessing speed.

Association

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Study;

The Nether-

lands

rial disease.

Cerebral infarcts

on MRI.

lesions of any

macrovascu-

lar event with

steeper esti-

mated life-

time decline

in processing

speed and

memory.

Manschot

et al. [25]

(2007)

Patients with

type 2 dia-

betes partici-

pating in the

Utrecht Dia-

betic En-

cephalopathy

Cross-sec-

tional, ob-

servational

122 Mean

66 ± 6

years

‘Any macrovascu-

lar event’ (MI,

stroke, and

surgery/endovas-

cular treatment for

coronary, carotid,

or peripheral arte-

rial disease) and

Composite score

from 11 cogni-

tive tests, esti-

mate of pre-mor-

bid ability, corti-

cal atrophy, and

white matter le-

Age, sex,

and esti-

mated

pre-mor-

bid ability

‘Any

macrovascu-

lar event’ and

infarcts both

associated

with steeper

estimated

lifetime cog-

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Study;

The Nether-

lands

cerebral infarcts on

MRI. Measure-

ment of cIMT.

sions nitive decline.

Finding on

‘any vascular

event’ attenu-

ated follow-

ing exclusion

of patients

with stroke.

For ‘any vas-

cular event’,

but not in-

farcts, associ-

ation per-

sisted in final

model adjust-

ing for age,

estimated pre-

Page 25: Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6 associated with lower cognitive function and steeper estimated lifetime decline (fully adjusted

morbid abil-

ity, hyperten-

sion, smok-

ing, and lipid-

lowering

drugs. No

finding for

cIMT.

ABI, ankle brachial index; ACCORD-MIND, Action to Control Cardiovascular Risk in Diabetes-Memory in Diabetes; ADVANCE,

Action in Diabetes and Vascular Disease: Preterax and Diamicron Modified Release Controlled Evaluation; CHD, coronary heart dis-

ease; cIMT, carotid intima-media thickness; CVD, cardiovascular disease; ECG, electrocardiogram; MCI, mild cognitive impairment;

MI, myocardial infarction; MMSE, Mini-Mental State Examination; MRI, magnetic resonance imaging; PAD, peripheral arterial dis-

ease; TIA, transient ischemic attack.

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{2 Column Table}

Table S4. Studies of natriuretic peptides and cognitive function in the general population and in type 2 diabetes

Study Sample Design Num-

ber

Base-

line

mean

age

Natriuretic

peptide

Cognitive

measures

Adjustment

variables

Association

with cogni-

tive function

Daniels et

al. [52]

(2011)

Rancho

Bernardo

Study; USA

Cross-sec-

tional, ob-

servational

950 Mean

77 ± 8

years

NT-proBNP,

categorized

as ‘high’

(≥450 pg/

mL) versus

‘low’ (<450

pg/mL) and

additionally

as quartiles

of the distri-

bution

MMSE, Trail-

Making Test,

and Category

Fluency.

‘Low’ perfor-

mance on

each defined

as MMSE

≤24, Trail-

Making ≥300

seconds, and

Age, sex,

education,

hypertension,

body mass

index, exer-

cise, alcohol,

smoking,

cholesterol,

and creatinine

‘High’ NT-

proBNP

group likely

to score low

on MMSE

and Trail-

Making com-

pared with

‘low’ group.

Findings sim-

ilar when

Page 27: Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6 associated with lower cognitive function and steeper estimated lifetime decline (fully adjusted

Category Flu-

ency ≤12

words. Cogni-

tive tests ad-

ditionally

used as quar-

tiles of re-

spective dis-

tribution.

excluding

participants

with stroke

and cardio-

vascular dis-

ease. Find-

ings for Cate-

gory Fluency

restricted to

largely unad-

justed analy-

ses. Addition-

ally increased

prevalence of

scoring in

lower quar-

tiles of cogni-

Page 28: Table 1: Studies of dyslipidaemia and cognitive function ... file · Web viewHigher IL-6 associated with lower cognitive function and steeper estimated lifetime decline (fully adjusted

tive scores

with increas-

ing quartiles

of NT-

proBNP (un-

adjusted

analyses).

Feinkohl et

al. [51]

(2013)

Patients with

type 2 diabetes

participating in

the Edinburgh

Type 2 Dia-

betes Study;

Scotland

4-year

prospective,

observa-

tional

1,066 Mean

68 ± 4

years

NT-proBNP

at baseline

MMSE, com-

posite score

from seven

cognitive

tests, and esti-

mate of pre-

morbid ability

Age, sex,

cholesterol,

blood pres-

sure, and

smoking

Association

of higher

baseline NT-

proBNP with

steeper late-

life cognitive

decline and

steeper esti-

mated life-

time decline.

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Finding on 4-

year decline

lost statistical

significance

when con-

trolled for

estimated

pre-morbid

ability or for

stroke, cIMT,

and ABI.

Kerola et

al.

[53] (2010)

Kuopio 75+

cohort;

Finland

5-year

prospective,

observa-

tional

464 Mean

80 ± 4

years

BNP at base-

line

Diagnosis of

AD, VaD,

and MMSE

Age, educa-

tion, and hy-

pertension

Association

of higher

BNP with

lower MMSE

and with

steeper de-

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cline on

MMSE (un-

adjusted

analyses).

Association

of higher

BNP and in-

creased risk

of AD and

VaD diagno-

sis during

follow-up

(adjusted

analyses).

Hiltunen et

al.

Kuopio 75+

cohort;

5-year

prospective,

observa-

601 Range

75-96

BNP at base-

line

Diagnosis of

dementia

Cross-sec-

tional analy-

ses: age, sex,

Presence of

any dementia

associated

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[54] (2013) Finland tional years medication,

heart failure,

and blood

pressure.

Prospective

analyses: age,

education,

and hyperten-

sion.

with higher

BNP in

youngest ter-

tile and lower

BNP in oldest

tertile.

Higher base-

line BNP

associated

with in-

creased risk

of dementia

during fol-

low-up in

youngest ter-

tile only.

Tynkkynen National FIN- 14-year 7,158 Mean NT-proBNP Medical Age, sex, Higher base-

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et al. [56]

(2015)

RISK Study;

Finland

prospective,

observa-

tional

48 ± 13

years

(range

25 to

74)

at baseline records for

diagnosis

with any de-

mentia or AD,

or dementia

medication

cholesterol,

body mass

index, is-

chemic heart

disease, and

diabetes

line NT-

proBNP asso-

ciated with

increased risk

of any inci-

dent dementia

across all

participants.

Finding

driven by

males. No

finding on

incident AD.

Vaes et al.

[55] (2009)

Leiden 85+

cohort;

The Nether-

lands

Cross-sec-

tional, ob-

servational

274 All 90

years

old

NT-proBNP

categorized

according to

sex-specific

MMSE. ‘Poor

cognitive

function’ de-

fined as

Height,

weight, renal

function, he-

moglobin,

No associa-

tion.

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tertiles of

distribution

MMSE <19. and cardio-

vascular med-

ication

ABI, ankle-brachial index; AD, Alzheimer’s disease; BNP, brain natriuretic peptide; cIMT, carotid intima-media thickness; FINRISK,

Finland Cardiovascular Risk Study; MMSE, Mini-Mental State Examination; NT-proBNP, N-terminal pro-brain natriuretic peptide;

VaD, vascular dementia.

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{2 Column Table}

Table S5. Studies of depression and cognitive function in type 2 diabetes

Study Sample Design Num-

ber

Base-

line

mean

age

Measure-

ment of de-

pression

Cognitive mea-

sures

Adjustment

variables

Association with

cognitive func-

tion

Cukier-

man-

Yaffe

et al. [13]

(2009)

Patients

with type 2

diabetes

participat-

ing in AC-

CORD-

MIND;

North

America

Cross-sec-

tional anal-

ysis of trial

on blood

pressure,

lipids, and

glycemic

control

2,977 Mean

63 ± 6

years

Scores ≥10

on 9-item

Patient

Health

Question-

naire or self-

reported

depression

Digit Symbol

Coding (primary

outcome),

MMSE, Rey Au-

ditory Verbal

Learning, and

Stroop (sec-

ondary out-

comes)

Age Association of

depression with

lower MMSE

scores. No find-

ings for other

cognitive tests.

Katon et

al. [60]

Patients

with type 2

3- to 5-year

retrospec-

19,000 Range

30-75

ICD codes

for diagnosis

ICD codes for

dementia in hos-

Sociodemo-

graphic factors,

Co-morbid de-

pression/diabetes

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(2012) diabetes

participat-

ing in the

Diabetes

and Aging

Study;

USA

tive, obser-

vational

years of depres-

sion/use of

anti-depres-

sants in hos-

pital records

pital records,

restricted to inci-

dent cases occur-

ring 3 to 5 years

after baseline

clinical risk

factors, health

risk factors, and

health use

associated with

increased risk of

dementia diagno-

sis compared

with diabetes

alone.

Sullivan

et al. [61]

(2013)

Patients

with type 2

diabetes

participat-

ing in AC-

CORD-

MIND;

North

America

40-month

trial on

blood pres-

sure, lipids,

and

glycemic

control

2,977 Mean

age 63

± 6

years

Scores ≥10

on 9-item

Patient

Health

Question-

naire at

baseline

Digit Symbol

Coding (primary

outcome),

MMSE, Rey Au-

ditory Verbal

Learning, and

Stroop (sec-

ondary out-

comes) at base-

line and 20 and

Age, sex, eth-

nicity, educa-

tion, glycemia

treatment arm,

blood pressure

versus lipid

treatment arm,

blood pressure

treatment, lipid

treatment, clini-

Association of

depression at

baseline with

steeper cognitive

decline across

cognitive tests.

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40 months cal center, car-

diovascular

event, body

mass index,

HbA1c, choles-

terol, smoking,

alcohol, and

insulin use

Trento et

al. [58]

(2012)

Patients

with 2

diabetes;

Italy

Cross-sec-

tional, ob-

servational

498 Mean

68 ± 7

years

Zung Self-

Rating De-

pression

Question-

naire

MMSE Age, sex, dura-

tion of diabetes,

HbA1c, and

insulin use

Statistically non-

significant trend

for association of

higher depression

scores with lower

MMSE scores

Watari et

al. [59]

(2006)

Patients

with type 2

Cross-sec-

tional, ob-

40 Range

30-80

years.

Clinical in-

terview to

diagnose

MMSE, 12 cog-

nitive tests result-

ing in composite

Age, sex, and

education

Statistically non-

significant trend

for lower overall

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diabetes;

USA

servational Mean

60 ± 12

years.

depression scores of atten-

tion/processing

speed, memory,

executive func-

tion, verbal mem-

ory, and non-ver-

bal memory

cognitive func-

tion and statisti-

cally significant

lower attention/

processing speed

in co-morbid

depression/dia-

betes group than

in no

depression/dia-

betes group.

ACCORD, Action to Control Cardiovascular Risk in Diabetes; ACCORD-MIND, ACCORD-MIND, Action to Control Cardiovascu-

lar Risk in Diabetes-Memory in Diabetes; ICD, International Classification of Diseases; MMSE, Mini-Mental State Examination.