Embed Size (px)
Citation preview
P3-183 THE IMPACT OF LORAZEPAM ON COGNITIONON APOE-�4 CARRIERS VERSUS NONCARRIERS
Cynthia M. Stonnington1, Peter J. Snyder2,3, Joseph G. Hentz1,Eric M. Reiman4,5, Richard J. Caselli1, 1Mayo Clinic, Scottsdale, AZ,USA; 2University of Connecticut, Storrs, CT, USA; 3Yale UniversitySchool of Medicine Child Study Center, New Haven, CT, USA;4University of Arizona, Tucson, AZ, USA; 5Banner Alzheimer’s Institute,Phoenix, AZ, USA. Contact e-mail: [email protected]
Background: The apolipoprotein E (APOE) �4 allele is a common Alz-heimer’s disease (AD) susceptibility gene. Previously, sleepiness was neg-atively correlated with memory in an exploratory cross-sectional study ofcognitively normal APOE-�4 homozygotes. If the induction of acute som-nolence by lorazepam were to expose neuropsychological deficits in at-riskindividuals, then it could be applied to a pharmacologic challenge forprediction of subsequent cognitive decline. Methods: Eighteen �3/4 het-erozygotes (HTZ) and 18 �4 noncarriers (NC), 50 to 65 years of age, allhealthy and cognitively normal, participated in the study. In a double blind,crossover design, we performed neuropsychological testing before, 2.5hours, and 5 hours after participants received a single 2 mg dose oflorazepam or placebo. Main outcome measures were the Groton MazeLearning Test (GMLT), Rey Auditory Verbal Learning Test (AVLT), and1-Back test. NC were matched to HTZ by age and years of education.Results: At 2.5 hours after the dose of lorazepam, the GMLT total errorsscore (P�.04) and the AVLT long-term memory (P�.01) and percentrecall (P�.005) measures of verbal memory were more impaired in HTZthan NC. A MANOVA comparing the vector of all six GMLT and AVLTmeasures for HTZ versus the vector of all six measures for NC yieldedP�.003 for 2.5 hours and P�.58 for 5 hours. No differences between HTZand NC were observed for measures of somnolence, speed, attention, orperformance on the 1-Back test at any of the time points. At 5 hours, HTZcontinued to make substantially more errors than NC (P�.17) only on theGMLT. Conclusions: Our study suggests that somnolence induced bylorazepam impairs verbal and visuospatial memory more in healthy mid-dle-aged APOE �4 carriers than noncarriers. The results warrant furtherresearch with a larger sample to determine if lorazepam induces an evengreater effect in �4 homozygotes, whether substantial lorazepam-inducedmemory impairment predicts subsequent onset of cognitive decline andconversion to mild cognitive impairment or AD, and whether adverseeffects of clinical lorazepam administration are greater in �4 carriers.
P3-184 CORRELATION BETWEEN MEDIAL TEMPORALATROPHY MEASURED BY A VOXEL-BASEDMORPHOMETRY SYSTEM AND SPECIFICDOMAINS OF COGNITIVE FUNCTION INALZHEIMER DISEASE
Hajime Takechi1, Yoshiyuki Hamakawa1, Atsuko Kokuryu1,Seiichi Furuya2, 1Department of Geriatric Medicine, Kyoto University,Kyoto, Japan; 2Louis Pasteur Center for Medical Research, Kyoto,Japan. Contact e-mail: [email protected]
Background: Recent advance in volumetric MRI technique provide occa-sion to measure brain atrophy in routine clinical practice. To study corre-lation between specific area of brain atrophy and cognitive impairmentwould be useful to understand pathophysiology of Alzheimer disease (AD).Methods: Twenty AD, 10 MCI and 12 patients who were finally diagnosedas normal were recruited to this study. Mean (SD) age of each group was75.9 (6.1), 74.3 (9.7) and 75.2 (7.0), respectively. All of the patientsunderwent volumetric MRI measurement on a 1.5-T system and neuropsy-chological examination. The voxel-based morphometry for MR imageswere performed using a voxel-based specific regional analysis system forAD (VSRAD, Hirata Y et al. Neurosci. Lett. 2005) in which specific voxelof interest, mainly in bilateral entorhinal cortex, was determined by groupcomparison of gray matter images for patients with very early AD at theMCI stage with those for healthy volunteers using SPM. Results: Mean(SD) of MMSE were 21.0 (3.3) for AD, 26.5 (2.1) for MCI and 28.9 (1.3)
for normal. Mean (SD) of VSRAD z-score were 3.23 (1.45) for AD, 1.77(1.08) for MCI and 1.38 (0.70) for normal. For the analysis of correlation,data of AD and MCI were combined. The analysis of correlation betweenVSRAD z-score and neuropsychological examination revealed the corre-lation between VSRAD z-score and MMSE (r� -0.433, p�0.05), wordfluency (vegetables, r� -0.538, p�0.005) and a subscale of MMSE (ori-entation for place, r� -0.518, p�0.01). Correlation was not observedbetween VSRAD z-score and other tests including category-cued memorytest (16 words), Trail Making Test A and B, Block design test of WAIS-R,Clock drawing test and subscales of MMSE related to recent memory(orientation for time, 3 words delayed recall). Conclusions: Medial tem-poral atrophy measured by voxel-based morphometry was correlated withMMSE and word fluency, but not with recent memory test, which isusually thought to reflect the function of medial temporal lobe. Slightatrophy in medial temporal lobe in very early stage of the disease may beresponsible for memory loss and the additional atrophy in it may predictdecline in language and general cognitive function.
P3-185 PREDICTORS OF LONGITUDINAL COGNITIVEDECLINE IN A COMMUNITY-BASED SAMPLE OFSPANISH- AND ENGLISH-SPEAKING OLDERADULTS
Sarah Tomaszewski Farias1, Dan Mungas1, Ladson Hinton1,Mary Haan2, 1University of California, Davis, Sacramento, CA, USA;2University of Michigan, Ann Arbor, MI, USA. Contact e-mail:[email protected]
Background: The identification of older adults who are at an elevated risk offuture decline in cognitive function is often difficult, particularly in individualsof an ethnic minority. We prospectively evaluated which baseline demo-graphic, neuropsychological and functional variables were most strongly as-sociated with future longitudinal decline in global cognitive function. Meth-ods: Participants were part of the Sacramento Area Latino Study on Aging(SALSA) (N � 696) and included cognitively normal, mildly impaired, anddemented cases. 63% were tested in Spanish. Average follow-up was fiveyears. Latent growth modeling of longitudinal data assessed the effects of age,gender, education, language (Spanish or English-speaking), acculturation,measures of neuropsychological function (i.e. verbal memory and confronta-tion naming) and functional status (as measured by the IQCODE) at baseline,on rate of change in global cognitive impairment (measured by the 3MS).Results: Lower education, Spanish-speaking status, lower scores on the neu-ropsychological tests and more impaired everyday function at baseline were allassociated with greater global cognitive impairment at baseline. In terms ofpredicting change, the only baseline demographic variable associated with afaster rate of decline was older age. Poorer baseline memory and naming wereassociated with global cognitive decline but this relationship did not remainsignificant after including age in the model. More functional impairment atbaseline was associated with a faster rate of decline and this effect wasindependent of age. Conclusions: Education and language of test administra-tion were associated with baseline cognitive performance but not change overtime, highlighting the importance of longitudinal follow-up in understandingthe effects of neurodegenerative disease in ethnically and educationally diversepopulations. Baseline functional status but not neuropsychological variableswere independently associated with both baseline and change in global cog-nitive impairment, suggesting functional problems may be a more sensitiveindicator of disease presence and progression than cognitive test performancein ethnically and educationally diverse samples.
P3-186 SUBJECTIVE MEMORY COMPLAINT INALZHEIMER�S DISEASE
Francisco A. C. Vale, Ari P. Balieiro Jr, Jose H. Silva-Filho,Behavioral Neurology Goup of Clinics Hospital of the Ribeirao PretoFaculty of Medicine, Ribeirao Preto, SP, Brazil. Contact e-mail:[email protected]
T574 Poster Presentations P3:
Background: Alzheimers disease (AD) patients usually are not aware oftheir memory loss and it is often necessary to count with information bycaregivers. An instrument to assess memory complaints by interviewingboth patient and caregiver could be useful to point out early problems. TheMemory Complaints Questionnaire (MCQ) has been developed in theBehavioral Neurology Group of Clinics Hospital of the Ribeira o PretoFaculty of Medicine, University of Sa o Paulo. MCQ consists of sevenquestions about memory problems, each of them with three alternatives,scored 0, 1 or 2. The objetive of this study was to verify whether MCQ isuseful to discriminate AD patients from healthy elderly people. Methods:Two groups were studied: 31 Alzheimer’s patients (AD) and 31 healthypeople named controls (C). They were paired by gender: 21 women (67.7%);by mean age: AD�72.77�1.42 y, C�72.74�1.45 y [t(60)�0.016, p(2-tailed)�0.987]; and by mean education: AD�2.32�0.55 y, C�2.35�0.57 y[t(60)�0.041, p(2-tailed)�0.967]. They were assessed through Mini-MentalState Examination (MMSE), digit span task, word list (immediate and laterecall, recognizing), verbal fluency test and MCQ. In AD group, the MCQ wasapplied to both patients (responding about themselves) and caregivers (re-sponding about patients). One looked for differences between the groups.Results: There were significant differences between groups in reference toMMSE scores [t(49)�4.327, p(2-tailed)�0.001]; digit span inverse[t(56)�3.490, p(2-tailed)�0.001]; word list immediate recall [t (56)�7.119,p(2-tailed)�0.001], late recall [t(55)�5.473, p(2-tailed)�0.001] and recogniz-ing [t(42)�4.124, p(2-tailed)�0.001]; verbal fluency semantic (animals)[t(55)�3.056, p(2-tailed)�0.004] and fonemic (”A” words) [t(43)�3.026,p(2-tailed�0.004]. Concerning to MCQ, there was no significant differencebetween AD (patients responding) and C groups [t(60)�0.646, p(2-tailed)�0.521] however there was significant difference between the AD(caregivers responding) [t(58)�6.278, p(2-tailed)�0.001] and C groups(t(58)�5.392, p(2-tailed)�0.001]; also, there was significant difference in-group between responses by patients and by caregivers [t(58)� -6,278, p(2-tailed) �0.001]. Conclusions: Alzheimers patients are not aware of theirmemory deficits and do not present subjective complaints. MCQ seems to bea suitable to assess memory complaints in AD patients since it also counts withsurrogate informants.
P3-187 FUNCTIONAL AND COGNITIVE ASSESSMENTFOR SEVERE DEMENTIA: COMPARISONBETWEEN INSTRUMENTS IN A BRAZILIANSAMPLE
Jose Roberto Wajman, Paulo Henrique Ferreira Bertolucci, FederalUniversity of Sao Paulo, Sao Paulo, Brazil. Contact e-mail:[email protected]
Background: The development of standardized and validated neuropsy-chological scales has had a significative impact in improving diagnosticprecision and in the characterization of the cognitive decline, but withdisease progression, the use of most scales for neuropsychological evalu-ation is hampered by the floor effect, with performance near null. Patientsare considered as “non testable” when their neuropsychological perfor-mance is much under the lower limit, indicating that there is a severecognitive decline, but, even at a very advanced stage, there might becognitive areas that are spared. Methods: This research was undertook tostudy the correlation between two tools for cognitive evaluation, Mini-mental State Examination-severe (MMSE-s) and severe Impairment Bat-tery (SIB) and the Bristol Daily Activities Functional Scale and the cor-relation between Bristol and the conventional MMSE. Our hypothesis isthat the MMSE-s and SIB have a better correlation with functional per-formance than MMSE in patients with moderately severe to severe demen-tia. To this end we did a stratification of scores for all the above scales. 50patients from the Behavioral Neurology Section - EPM-UNIFESP - wereevaluated. Mean age was 76,8 � 7,9 (range 57 to 95) and 32% were males;mean education was 5,0 � 2,3 years (range 4 to 15); mean disease durationwas 3,9 � 1,5 years. Results: Preliminary results in a small sample drawnfrom the study group do indicate a difference between the three cognitivescales. SIB and MMSE-s had a better correlation with functional score than
MMSE, and MMSE-s had a correlation slightly better than SIB. Conclu-sions: These data indicate that it is possible a follow up of dementiapatients up to severe stage as long as adequate instruments are used. On theother hand, conventional tools like MMSE might not have a correlationwith functional status, and thus might not reflect patient’s daily life. Theresults are in accordance with those of other centers and meet a need of ourcountry with respect to the evaluation and follow up of severe dementiapatients. Considering that survivalin dementia patients is increasing andnew therapies are being tried, this issue will become increasingly crucial.
P3-188 UNAWARENESS OF POOR OLFACTORYFUNCTION IS ASSOCIATED WITH REDUCEDCOGNITIVE FUNCTIONING IN HEALTHYMIDDLE-AGED AND OLDER ADULTS
Eike I. Wehling1, Astri Johansen Lundervold1, Thomas Espeseth2,Ivar Reinvang2, Steven Nordin3, 1University of Bergen, Bergen,Norway; 2University of Oslo, Oslo, Norway; 3University of Umeå,Umeå, Sweden. Contact e-mail: [email protected]
Background: Olfactory dysfunction increases significantly with age (Murphy,2002) while prevalence rates of self-reported olfactory dysfunction only risemarginally (Nordin, 2004). Consequently, self-reports are unreliable indicatorsof functioning in this domain of perception. Concerning cognitive functioningboth unawareness of deficits (Barrett, 2005) but also complaints about im-paired function (Koivisto, 1995) are well known in aging individuals andpatients suffering from neurological diseases, e.g. Mild Cognitive Impairment(MCI) or Alzheimer’s disease (AD). Devanand (2000) suggested that impairedawareness of olfactory and functional deficits in MCI patients may possiblyserve as diagnostic marker for early detection of AD. Our aim was to inves-tigate unawareness of poor olfactory functioning, its association with cognitiveperformance, and self-reported memory functioning in healthy middle-agedand older adults. Methods: A total of 251 participants (68% women), aged45-80 years, were assessed with the Scandinavian Odor Identification Test, acomprehensive battery of neuropsychological tests, and the Everyday MemoryQuestionnaire (EMQ). Divided into three age groups, analysis revealed that thenumber of participants having an olfactory dysfunction increased significantlywith age ((2) (2) � 12.1, p � 0.02). The number that failed to rate theirolfactory function correctly also increased with age, but remained statisticallynon-significance ( 2 (2) � 5.55, p � 0.06). Performance on neuropsycho-logical tests indicated that persons failing to properly rating their olfactoryfunction showed lower performance on several tests, i.e. verbal memoryfunctioning and processing speed. Results: Our results suggest that unaware-ness of an olfactory dysfunction is associated with lower cognitive perfor-mance on tests known to be sensitive to brain dysfunction, e.g. dementia.However, the unaware participants did not obtain elevated scores on the EMQbeing a potential measure for cognitive complaints. Conclusions: These find-ings support the notion that unawareness, in both cognitive and sensorydomains, should be included in further studies of early signs of pathologicalaging.
Barrett, A.M. et al. (2005). Neurology, 64, 693-697.
Devanand, D.P. et al. (2000). American Journal of Psychiatry, 157, 1399-1405. Murphy, C. et al. (2002). Journal of the American Medical Associ-ation, 13, 2307-2312.
Nordin, S. Et al. (2004). Acta Laryngol., 124, 1171-1173.
Koivisto, K. Et al. (1995). Neurology, 45, 741-747.
P3-189 THE UTILITY OF THE CLOCK DRAWING TEST:MAKING A DIFFERENTIAL DIAGNOSISBETWEEN ALZHEIMER’S DISEASE ANDVASCULAR DEMENTIA
April Wiechmann1, James Hall2, 1University of North Texas, Denton,TX, USA; 2University of North Texas Health Science Center, Ft. Worth,TX, USA. Contact e-mail: [email protected]
T575Poster Presentations P3:
