Cognitive impairment in well-treated cohorts › ... ›...
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Cognitive impairment in well-treated cohorts
Dr Jonathan Underwood Imperial College London July 2016
What am I going to talk about?
• Background
• POPPYstudy
• COBRAstudy(POPPYneurologicalsub-study)
• Conclusions
Data: Public health England 2014 report
About 108,000 people living with HIV in the UK
The cohort is ageing
PHEHIVintheUK;2014report
We all age… … some quicker than others
✔ ✖
What do we know about co-morbidities in well-treated patients?
Clin Infect Dis. 2014 Dec 15;59(12):1787-97
Significantly more hypertension, angina, MI, liver disease, renal failure and cancer in HIV-infected subjects
Number of comorbidities per patient
Mean number of age-associated non-communicable comorbidities0.68 0.80 1.03 1.15 1.47 0.89 1.35 1.52 1.65 2.04
Number of participants166 108 70 53 34 159 111 86 62 52
HIV negative HIV positive100
Num
ber,
%
80
60
40
20
0
3+210
How do we age?
Cognitive impairment
Cerebrovascular disease
Osteoporosis
Kidney dysfunction
Cardiovascular disease
Liver dysfunction
Severe
Mild
AsymptomaAc
0%
5%
10%
15%
20%
25%
30%
35%
Pre-1997
AnAretroviraleraAdaptedfromMcArthuretal.,AnnNeurol67,699-714,2010.
What’s the prevalence of cognitive impairment?
Key questions
Whatistheprevalenceinwell-treatedcohorts?WhatarethecharacterisJcsofimpairmentinwell-treatedcohorts?WhatarethemechanismsofcogniJveimpairmentinwell-treatedindividuals?
POPPY – preliminary findings
387subjectsaged>50enrolled:– 290HIV+– 97demographicallycomparableHIV-controls
AllparJcipantsansweredthe3EACScogniJvecomplaintsscreeningquesJonsandcompletedquesJonnairesdetailing:
• Physical&mentalhealth(SF-36)• AcJviJesofdailyliving(LawtonIADL)• Depression(PHQ-9,CES-D)• Falls• SexualfuncJon
Methods cont…
AllweretestedwiththeCogStatecogniJveba\ery(seetable):RawscoresconvertedtodemographicallyadjustedTscoresusingtheHIV-groupasthereferencepopulaJon.CogniJveimpairmentdefinedusingpublishedmethods(seetable):
CogniAvedomain Testadministered
ANenAon/WorkingMemory OnebacktaskTwobacktask
ExecuAveFuncAon GrotonMazeLearningtestSetshieingtask
Processingspeed DetecJontaskVisualANenAon IdenJficaJontask
VerbalLearning/Memory InternaJonalShoppinglisttaskInternaJonalShoppinglisttask–delayedrecall
VisualLearning/MemoryConJnuouspairedassociatelearningtestGrotonMazeLearningtest–delayedrecallOnecardlearningtask
DefiniAon DefiniAonofabnormaltestresult
DefiniAonofabnormalcogniAvedomain
Affecteddomains
FrascaAcriteria1 1SDbelownormaJvemean
meandomainperformanceabnormal
≥2
Globaldeficitscore(GDS)2
GDSscore≥0.5(theGDSscoreisobtainedbyconverJngdomainTscoresintodeficitscorerangingfrom0to5andthenaveragingthem)
MulAvariatenormaAvecomparison(MNC)3
Hotelling’sT2staJsJc(analogoustoamulJvariatet-testperformedonallcogniJvetestssimultaneously)exceedsacriJcalvalue
1AnJnoriAetal,Neurology(2007);2CareyCLetal.JClinExpNeuropsyc(2004);3HuizengaHMetal,Neurospychologia(2007)
Baseline characteristics
HIV+(n=290) HIV-(n=97) p-value Gender,n(%) <0.001 Female 34(11.7%) 33(34.0%) Male 256(88.3%) 57(66.0%)
Ethnicity,n(%) 0.46 Black-African 37(12.8%) 9(9.3%) White 253(81.2%) 88(90.7%)
Age(years),median(Q1,Q3) 57(53,62) 58(54,62) 0.22 CD4count(cells/mm3),median(Q1,Q3) 610(479-780) N/A LikelyrouteofHIVtransmission,n(%) N/A MSM 229(79.0%) Heterosexualsex 61(21.0%)
ReceivinganAretrovirals,n(%) 238(82.1%) N/A
Prevalence of cognitive impairment
30.0% 34.5% 22.1%16.5% 14.4% 7.2%0%10%20%30%40%
FRASCATI GDS MNC0%5%10%15%20%
25 35 45 55
GlobalT-score
≥50HIV- ≥50HIV+ p-valueMedian(IQR): 50.8(47.5,54.1) 48.6(43.5,52.3) <0.001
Prevalence
OR(95%CI): 2.17(1.20,3.92) 3.12(1.69,5.78) 3.64(1.61,8.24)p-value: 0.011 <0.001 0.001
30.0%34.5%
22.1%16.5% 14.4%
7.2%
0%
10%
20%
30%
40%
FRASCATI GDS MNC
≥50HIV+ ≥50HIV-
Cognitive scores by domain
BoxplotsofdemographicallyadjustedcogniAvedomainT-scoresbyHIV-serostatus.PvaluescalculatedusingWilcoxonranksumtest.
Association with symptoms
62% 75%38% 25%CI NOTCI
p=0.02
Memoryloss Reasoning ANenAon
59% 75%41% 25%CI NOTCI
p=0.02
60% 77%40% 23%CI NOTCI
p<0.01
60% 62%40% 38%CI NOTCI
p=0.77
57% 63%43% 37%CI NOTCI
p=0.42
57% 64%43% 36%CI NOTCI
p=0.24
69% 72%31% 28%CI NOTCI
p=0.59
66% 73%34% 27%CI NOTCI
p=0.28
64% 75%36% 25%CI NOTCI
p=0.0761.8% 38.2%
Neverorhardlynever Yes,definitely
FRASCATI GDS MNC FRASCATI GDS MNC FRASCATI GDS MNC
Associations with summary health scores
Ji\erplotsofSF-36summaryscoresformentalandphysicalhealthforthosewith(triangles)vs.without(circles)cogniJveimpairmentforthethreediagnosJccriteria.Blacklinesindicatemedians.PvaluescalculatedusingWilcoxonranksumtest.
Conclusions from POPPY
CogniAveimpairmentismorecommoninHIV-posiAveindividualsBUT:• It’sgenerallymild• CorrelatespoorlywithsymptomsThismaybedueto:• over-reporJngofsymptoms• subjecJvityofcogniJvescreeningquesJonsandotherpaJentreportedmeasures• lackofaclearrelaJonshipbetweensubjecJveexperienceandobjecJvemeasuresofcogniJvefuncJon
Understanding cognitive impairment
Neurologicalsub-study
Asautopsydataisrarenowweneedtouseothertoolstostudydiseasemechanisms• Neuroimaging• CSFbiomarkers
InclusioncriteriaHIV+group(n=134)• documentedHIVinfecJon• age≥45yearsatstudyentry• documentedplasmaHIVRNA<50
copies/mL>12monthsoncART
HIV-group(n=79)• documentednegaJveHIVtestinpast6
monthsoratscreening• age≥45yearsatstudyentry
Exclusioncriteria• currentmajordepression(PHQ-9≥15)• chronicneurologicaldiseases• historyofsevereheadinjury• historyofcerebralinfecJons(including
AIDSdefiningillnesses)• severepsychiatricdisease
COBRA (neurological sub-study)
Allunderwent:cogniAvetesAng,MRIscanning(severalmodaliJes)andCSFexaminaJon
CogniAvebaNery(tesAngaNenAon,execuAvefuncAon,language,memory,motorfuncAonand
processingspeed)
Methods