Embed Doc
Copy Link
Readcast
Collections

CommentGo Back

Download

Arq Neuropsiquiatr 2007;65(4-B):1154-11571154

SUBCLINICAL ENCEPHALOPATHY IN CHRONICOBSTRUCTIVE PULMONARY DISEASE

Olga Maria Pinto de Lima

1,2

, Ricardo de Oliveira-Souza

1,2

, Omar da Rosa Santos

,Pedro Araújo de Moraes

, Leonardo Fontenelle de Sá

, Osvaldo J.M. Nascimento

ABSTRACT -

Background:

Clinical and experimental evidence suggests that chronic obstructive pulmonarydisease (

COPD

) is associated with a variety of mental symptoms that range from cognitive slowing to mentalconfusion and dementia.

Purpose:

To test the hypothesis that COPD leads to cognitive impairment in theabsence of acute confusion or dementia.

Method:

The global cognitive status of 30 patients with COPDwithout dementia or acute confusion and 34 controls was assessed with a Brazilian version of the Mini-Men-tal State Exam (MMSE).

Results:

The MMSE scores were significantly lower in the patient group and inverse-ly related to the severity of COPD. This finding could not be attributed to age, education, gender, daytimesleepiness, hypoxemia, chronic tobacco use, or associated diseases such as diabetes, depression, high bloodpressure or alcoholism.

Conclusion:

These results suggest the existence of a subclinical encephalopathy ofCOPD characterized by a subtle impairment of global cognitive ability.KEY WORDS: chronic obstructive pulmonary disease, mini-mental state exam, subclinical encephalopathy.

Encefalopatia subclínica na doença pulmonar obstrutiva crônica

RESUMO -

Contexto:

Evidências clínicas e experimentais sugerem que a doença pulmonar obstrutiva crônica(DPOC) se associa a sintomas neurocomportamentais que variam da lentidão cognitiva à confusão mentale à demência.

Propósito:

Testar a hipótese de que a DPOC pode comprometer a cognição na ausência deestado confusional agudo ou de demência.

Método:

O estado cognitivo global de 30 pacientes com DPOCsem demência e sem confusão mental aguda e o de 34 controles foi examinado com a versão brasileira doMini-Exame do Estado Mental (MEEM).

Resultados:

As pontuações no MEEM mostraram-se significativa-mente mais baixas nos pacientes, e inversamente relacionadas à gravidade da DPOC. Este achado não pôdeser atribuído a diferenças de idade, escolaridade, sonolência diurna, hypoxemia, tabagismo crônico, ou adoenças associadas como diabetes, depressão, hipertensão arterial ou alcoolismo.

Conclusão:

Estes resul-tados sugerem a existência de uma encefalopatia subclínica da DPOC caracterizada por comprometimentosutil da capacidade cognitiva global.PALAVRAS-CHAVE: doença pulmonar obstrutiva crônica, mini-exame do estado mental, encefalopatia sub-clínica.

Escola de Medicina e Cirurgia, Universidade Federal do Estado do Rio de Janeiro, Brazil;

Programa de Pós-Graduação em Neuro-logia e Neurociências da Universidade Federal Fluminense, Niterói RJ, Brazil.Received 2 August 2007, received in

ﬁ

nal form 14 September 2007. Accepted 3 October 2007.

Dra. Olga Maria Pinto de Lima - Rua Antônio Basílio, 204 / 801 - 20511-190 Rio de Janeiro RJ - Brasil. E-mail: ompl@oi.com.br

The neurological manifestations of hypercapnic re-spiratory disease were

ﬁ

rst described as a collection ofmanifestations consisting of headache, papilledema,fatigue, confusion and asterixis, eventually progress-ing to stupor and coma

. This clinical worsening is par-alleled by a progressive slowing of the basic frequen-cies of the scalp electroencephalogram. Pathophysio-logically the manifestations of hypercapnic respirato-ry disease re

ﬂ

ect a progressive reduction of the alve-olar surface of gas exchange, with respiratory acido-sis and a concomitant retention of arterial CO

. Thecritical role of CO

retention in the pathophysiologyof headache and papilledema (the pseudotumor syn-drome), as well as of muscle twitching, sleepiness andconfusion (the syndrome of metabolic encephalopa-thy), is emphasized in the designation of this symp-tom-complex as “CO

narcosis”

.In contrast to what is usually observed in advancedor unstable chronic obstructive pulmonary disease(COPD), the cognitive status of clinically stable pa-tients has been comparatively less studied. Becausesuch patients are awake and oriented they may con-vey a cursory impression that they are cognitively in-tact. However, indirect evidence suggests that thismay not be accurate, at least in some cases. Sever-al reports indicate that a mild encephalopathy is afairly common occurrence in hepatic, thyroid and re-nal disease

3-6

. Because these milder cognitive chang-

Arq Neuropsiquiatr 2007;65(4-B)1155

Encephalopathy: chronic obstructive pulmonary diseaseLima et al.

es do not cross the diagnostic threshold for a formaldiagnosis of acute confusional state or dementia

, theexpression “subclinical”, or “subthreshold” enceph-alopathy has been employed as a shorthand refer-ence. The subclinical encephalopathy of these condi-tions is characterized by mental slowing with a pre-served global cognitive status. In particular, temporaland spatial orientation is, as a rule, entirely normal,yet some degree of cerebral impairment of a magni-tude suf

ﬁ

cient to compromise routine activities maystill be detected by sensitive tests.The aim of the present investigation was to testthe hypothesis that clinically stable patients withCOPD without overt cognitive symptoms may never-theless present subtle cognitive impairments.

METHOD

Twenty men and 10 women with COPD and 34 controls(10 men and 24 women) without respiratory disease partic-ipated in the study as nonpaid volunteers after providingwritten informed consent. Between 2000 and 2006 patientswith a clinical and spirometric diagnosis of COPD

8-10

were re-cruited from the outpatient sector of the Service of Respi-ratory and Lung Diseases of the Gaffrée e Guinle UniversityHospital (HUGG). They were clinically stable, normally en-gaged in their routine daily life activities, and had not beenadmitted to a hospital or treated with antibiotics in the pre-ceding 30 days. These criteria selected only those patientswho were in an optimal clinical condition during a relativelyprotracted period of stability, thus excluding patients withunstable disease. The control group was composed of hos-pital employees and acquaintances of the authors withouta history or current clinical evidence of chronic respirato-ry disease. All medications currently in use, as well as redblood cell counts, blood glucose, blood urea nitrogen, bloodpressure levels, and drinking habits were noted in each case.The study did not receive funding from research agenciesand was conducted in the HUGG as part of the post-doctor-al project of one of the authors (OMPL). The project was ap-proved by Ethics Committee of the HUGG and the NationalCouncil of Education and Research (CONEPE).

Respiratory measures –

The O

saturation (SaO

) at rest,an index of alveolar gas exchange, was measured with apulse oximeter immediately before the administration ofthe MMSE. COPD was staged according to individual FEV

values obtained after pharmacological bronchodilatationon the following 4-point ordinal scale: Stage 0: absence ofdisease; Stage 1: FEV

>60%; Stage 2: 40%

≥

FEV

≤

60%; andStage 3: FEV

<40%.

Cognitive, behavioral and socio-occupational measures –

The Mini-Mental State Exam (MMSE) was used to gaugethe global cognitive status as well as to ascertain that noparticipant was either demented or confused

. From 2003 tothe present we adopted the of

ﬁ

cial Brazilian version of theinstrument

. Dementia, Acute Confusional State (Delirium)and Depression were diagnosed following the criteria of theAmerican Psychiatric Association

and depression was addi-tionally staged with the Beck Depression Inventory

. Day-time somnolence was assessed with the Epworth SleepinessScale

. Alcohol abuse was assessed with the CAGE ques-tionnaire

. The cumulative cigarette consumption (num-ber of cigarettes smoked during a lifetime) was estimat-ed based on the number of smoking years and the yearlytobacco consumption. The overall socio-occupational lev-el was assessed with the Global Assessment of Function-ing (GAF) Scale

Statistical analyses

–

All results are expressed as meansand standard deviations (x±sd). The signi

ﬁ

cance of differ-ences between means was assessed with analyses of vari-ance (ANOVA). Associations between dimensional and cat-egorical variables of interest were evaluated, respectively,with the Pearson correlation coef

ﬁ

cient (r) and with the

²test. A two-tailed critical value (

) of 0.05 was adopted as asigni

ﬁ

cance threshold for all statistical tests. The effect sizeand statistical power of statistical tests of interest were cal-culated with G*Power

RESULTS

The results are summarized in the Table. No signif-icant differences were found between groups in re-lation to age (p>0.89), education (p>0.33), regular al-cohol consumption (p>0.77), depression (p>0.07), andsystolic (p>0.12) or diastolic (p>0.26) arterial bloodpressure. However, there were more women amongcontrols than among patients (p=0.01). As expect-ed, there were more smokers in the patient group(p<0.001). The MMSE scores were signi

ﬁ

cantly low-er in patients than in controls (p<0.001) and inverse-ly related to the severity of COPD (r= –0.49, p<0.001).Socio-occupational functioning was also inverselyrelated to the severity of COPD (r= –0.47, p<0.001)and positively related to the MMSE scores (r=0.41,p<0.01). The statistical power (

) and effect size (d) ofthe mean difference between groups on MMSE per-formance were, respectively 0.95 (“high”) and 0.74(“medium to large”).

DISCUSSION

The main findings of the present investigationcan be summarized as follows: (i) patients with clini-cally stable COPD without dementia or acute confu-sion may nonetheless show global cognitive impair-ment, as revealed by comparatively lower scores onthe MMSE, (ii) the MMSE was inversely related to theseverity of COPD, and (iii) this cognitive impairmentwas not due to age, education, daytime sleepiness,hypoxemia, tobacco consumption, and associated dis-eases such as diabetes, depression, high blood pres-sure, and alcoholism.

Arq Neuropsiquiatr 2007;65(4-B)1156

Encephalopathy: chronic obstructive pulmonary diseaseLima et al.

These

ﬁ

ndings acquire additional relevance forthe following reasons. Firstly, given the relativelylow sensitivity of the MMSE, it is surprising that anydifferences in cognitive status between groups werenoted at all. One implication of this

ﬁ

nding is that theglobal cognitive level of our patients may in fact havebeen lower than it would be if they did not sufferfrom COPD. This decline is subtle and may easily passunnoticed in routine consultations. Secondly, furtherstudies are necessary to verify whether this relativedecline has a direct adverse in

ﬂ

uence on daily life, be-cause, if it does, cognitive status may be an indepen-dent target for treatment. Indirect evidence in favorof this possibility was the veri

ﬁ

cation of signi

ﬁ

cantassociations between MMSE, COPD, and GAF scores.Our study has several limitations that can be tack-led in future research. The ease of administration ofthe MMSE is counterbalanced by its relative lack ofsensibility and speci

ﬁ

city. For example, studies ad-dressing speci

ﬁ

c cognitive domains (such as executiveperformance, attention, cognitive speed) might giveimportant clues on which cognitive processes best ex-plain the performance of our patients on the MMSE.Some studies do indicate that patients with COPDpresent memory impairment, and this could explainat least in part the decline in the MMSE

19-25

. Howev-er, the different clinical characteristics of our patientsand of the patients of the aforementioned studiespreclude direct comparisons. Another limitation wasthe lack of arterial measures of paCO

and paO

,which would allow more stringent conclusions onthe mechanisms by which cognition fails in such cases.Regardless the exact pathophysiological mecha-nisms at play our results support the proposal thata subclinical encephalopathy may indeed exist in atleast a few cases of COPD. As far as we are aware,the concept of subclinical encephalopathy has not asyet been explicitly extended to COPD. The results ofthe present study, although admittedly preliminary,suggest that the concept of subclinical encephalopa-thy might be extended to patients with COPD. Thisidea would gain further support if such patients were

Table. Demographic, clinical, and cognitive

ﬁ

ndings in patients with COPD and controls.

ControlsCOPDTotal NMalesFemales

341024302010Age (in years)66±865±8Education (in years)5.9±4.25.5±4.4Diabetes01High blood pressure1511Current systolic pressure 141±24131±21Current diastolic pressure 84±1081±12Drinks alcohol regularly98CAGE

(0-4)0.30±0.700.33±0.76History of tobacco smoking

722Age at start (in years)

30±716±12Cumulative cigarette consumption (cigarettes/life)

81,565±194,019455,793±284,140SaO

(%)



95±2FEV



42,1±15,9Polycythemia



4Hematocrit (%)



42,5±4,1MMSE

(0-30)28.1±1.926.0±3.5Depression (DSM-IV)37Beck inventory (0-39)7.1±5.910.5±8.3Daytime sleepiness (0-24)35Epworth scale (0-24)5.5±3.36.7±3.7Global assessment of functioning