Neuropsychological detection of dementia in ... - Alzheimer's & Dementia

16 downloads 88064 Views 58KB Size Report
Jul 16, 2012 - paired free recall and recognition memory), mild aphasia (i.e., anomia, ... assessment of cognitive functions can be improved by adapting the tools to ... association of cognitive testing and informant questionnaire is the best option .... Hanna Cho, Sang Won Seo, Jung-Hyun Kim, Young Noh, Geon Ha Kim,.
Symposia: S2-01: Multicultural Issues In Neuropsychological Assessment

MONDAY, JULY 16, 2012 SYMPOSIA: S2-01 MULTICULTURAL ISSUES IN NEUROPSYCHOLOGICAL ASSESSMENT S2-01-01

NEUROPSYCHOLOGICAL ASSESSMENT OF DEMENTIA ON GUAM

David Salmon, UCSD, La Jolla, California, United States. Background: Parkinson-Dementia Complex (PDC) is a neurodegenerative disorder that occurs almost exclusively in the indigenous Chamorro population on the Marianas island of Guam. Parkinsonism typically occurs concomitantly with the onset of dementia and is essentially identical to that of idiopathic Parkinson’s disease (PD). PDC is a tauopathy characterized by neurofibrillary tangles and neuron loss in a number of brainstem nuclei, limbic structures, and association cortices. There is little deposition of amyloid and alpha-synuclein pathology is rare. A pure dementia syndrome without significant motor abnormality is also quite prevalent in Guam’s elderly Chamorro population. Little is known about the underlying neuropathology of this late-life Guam dementia (GD), but it has been variably associated with Alzheimer’s disease (AD) or PDC pathology in a handful of cases. The dementia syndromes of PDC and GD have not been carefully characterized, but clinical reports suggest that they usually begin with forgetfulness, disorientation, and difficulty with problem solving and calculations. Methods: A battery of culturally-adapted neuropsychological tests was administered to Chamorro patients with clinically-diagnosed PDC (n ¼ 37) or GD (n ¼ 55), and to healthy Chamorro elderly control (EC) subjects (n ¼ 45). The tests were chosen to be sensitive to cognitive changes associated with PD or AD, and included measures of memory, attention, language, executive function, visuospatial ability, and psychomotor speed. Results: Patients with PDC and GD were impaired relative to EC subjects on all neuropsychological tests and exhibited similar profiles of deficits that included frank amnesia (i.e., poor learning, abnormally rapid forgetting, impaired free recall and recognition memory), mild aphasia (i.e., anomia, verbal fluency impairment), executive dysfunction, and constructional apraxia. This qualitative pattern of deficits resembles that of the cortico-limbic dementia syndrome of AD. However, some features of fronto-striatal dysfunction were also evident (i.e., set shifting deficits, equally poor semantic and letter fluency), even in those without Parkinsonism. Conclusions: The striking similarities in the cognitive profiles associated with PDC and GD suggest that the two conditions may reflect different points along a spectrum of a single disease in the Chamorro population. The dementia syndrome appears largely corticolimbic in nature and may reflect the tauopathy common to both disorders. S2-01-02

BARRIERS TO THE COGNITIVE ASSESSMENT OF DEMENTIA IN INDIA

Jacob Kuriakose, Sukumaran Shaji, Alzheimer’s and Related Disorders Society of India, Comprehensive Dementia Care, Ernakulam, Kunamkulam, Kerala, India. Background: Assessment of cognitive functions is an integral part of evaluation of elderly persons. Cognitive assessment is commonly used for the screening for cognitive impairment, differential diagnosis of causes, rating severity of the disorder and monitoring the disease progression. There is a well documented tendency for cognitive tests to underestimate the abilities of older people in developing countries like India. This gives rise to a substantially higher risk of mistaken diagnosis of dementia. Methods: Epidemiological studies conducted in India since 1990 were reviewed with the focus on cognitive assessment methods used in these studies. Cognitive assessment tools developed in western context were translated and adapted for the purpose of cognitive screening in general. Difficulties encountered while assessing the cognitive functions were analyzed. Results: Specificity was low with many cognitive screening tools.2. Cognitive screening test like Mini Mental State Examination can overestimate cognitive impairment.3. Language barriers and low education can lead to difficulties in assessment.4. Low education can result in inappropriate response due to educational misinterpretation as opposed to cognitive dysfunction.5. Dementia is consid-

P227

ered as a part of normal aging.6. Lack of familiarity with western calendar can make mistakes in assessing orientation. 7. Cultural beliefs about dementia are a barrier to its acceptance and diagnosis. 8. Factors like sensory impairments, depression, other psychiatric and neurological disorders and physical disabilities can make cognitive assessment difficult. Conclusion: Clinicians and health care workers face several barriers in assessment of cognitive functions of the elderly persons in India Accuracy of assessment of cognitive functions can be improved by adapting the tools to suit the socio-cultural setting, adjustment of cut points, translation and replacement of culture specific items and development of culture free tests. S2-01-03

COGNITIVE TESTING OF ILLITERATE ELDERLY IN BRAZIL

Ricardo Nitrini, University of S~ao Paulo, S~ao Paulo, Brazil. Background: The assessment of illiterates for the diagnosis of mild cognitive impairment or dementia is more complex than that of literate individuals. It is estimated that there are approximately 800 million illiterate adults worldwide (14 million in Brazil), with a large proportion of elderly among them. This issue is still important for developing countries and even for developed countries when evaluating individuals who do not understand the written system of the country. Methods: A search in Medline and LILACS was performed using the following keywords: illiteracy, dementia, cognitive impairment and cognitive evaluation in English and in Portuguese languages to identify the most widely used tests for the diagnosis of dementia in illiterate individuals in Brazil. Results: The most widely used test in Brazil for the diagnosis of cognitive impairment in the illiterate is the Mini-Mental State Examination with adjusted cut-off score (18 is the most accepted one). Semantic verbal fluency tests (animals/1 minute) with a cut-off score of 9 is also frequently used. The memory test for objects (FOME) and memory test of simple drawings (BCSB) have been used in research and in clinical practice. The clock drawing test is not recommended for the diagnosis of dementia in low educated or illiterate individuals. The combined use of cognitive tests with informant questionnaires showed the highest accuracy. Among the questionnaires the Functional Activities Questionnaire and IQCODE are the mostly used. The Neuropsi and CERAD batteries may be used with adjusted cut-off scores. Conclusions: The association of cognitive testing and informant questionnaire is the best option for the diagnosis of cognitive impairment in illiterate individuals in Brazil. S2-01-04

NEUROPSYCHOLOGICAL DETECTION OF DEMENTIA IN HISPANIC POPULATIONS

Dan Mungas, University of California, Davis, Sacramento, California, United States. Background: Cognitive impairment is the defining feature of dementia associated with Alzheimer’s disease and related diseases of aging. As demographic diversity increases there is a rapidly developing need for clinical assessment methods to evaluate brain function and consequences of brain injury in individuals from diverse cultural and linguistic backgrounds, and this is especially true for the rapidly growing population of older Hispanics. Neuropsychological assessment of Hispanics presents challenges that apply to other minority groups, but in addition, presents unique challenges related to language, culture, and life experiences. As a quantitative discipline, neuropsychology has much to offer in terms of standardized and empirically validated assessment procedures that can be used with diverse patients groups. This presentation will address important issues involved in constructing neuropsychological tests that can be used effectively in detecting cognitive impairment and dementia in older Hispanics. Methods: Modern psychometric methods based on item response theory were applied to a large linguistically and ethnically diverse sample to create a neuropsychological test battery, the Spanish and English Neuropsychological Assessment Scales (SENAS) with matched English and Spanish language versions. Sensitive and linear measurement across a broad ability range from fully normal to demented was emphasized. Sensitivity to cognitive impairment and cognitive decline and influences related to demographic characteristics have been tested in cross-sectional and longitudinal studies. Results: Empirical results evaluating measurement bias, sensitivity to clinical disease, and relations

P228

Symposia: S2-02: Phenotypical Heterogeneity In Alzheimer’s Disease

with brain structure will be reviewed. Sensitivity to the earliest manifestations of diseases causing dementia will be emphasized. Issues of age, education, and race/ethnicity adjustment of test scores will be addressed, and limitations of one-time assessments for making complex clinical decisions will be discussed. Conclusions: Effective measurement for any population begins with careful item development and empirically guided selection so that the test is relevant to the population and measurement goals. Modern psychometric methods coupled with well-designed data collection provide a quantitative foundation for effective measurement in diverse older groups including older Hispanics. SYMPOSIA: S2-02 PHENOTYPICAL HETEROGENEITY IN ALZHEIMER’S DISEASE S2-02-01

UNDERSTANDING (ENDO)PHENOTYPICAL HETEROGENEITY: THE ROLE OF AGE AND APOE

Wiesje Van der Flier, Philip Scheltens, VU University Medical Center, Amsterdam, Netherlands. Background: It is increasingly recognized that AD is a heterogeneous disorder. Age-at-onset and APOE genotype influence cognitive phenotype, but it is unclear by which mechanisms they exert their effect. Different aspects of neuropathology, i.e. more upstream as reflected by amyloid-PET, or more downstream as reflected by EEG connectivity or volumetric MRI may serve as endophenotypes, providing clues for the variability in pathways leading to the clinical syndrome of AD. We investigated differences according to age-at-onset and APOE genotype with respect to PET, EEG connectivity, and MRI. Methods: An overview is given of how age-at-onset and APOE genotype impact different aspects of manifestation of the disease. Measures for Alzheimer pathology include Pittsburgh compound-B (PIB) PET for amyloid burden, FDG PET for glucose metabolism, electroencephalogram (EEG)-based phase lag index as measure of functional connectivity, and voxel-based morphometry as measure of neurodegeneration. Results: Comparing younger and older patients, we found a different distribution of both amyloid burden and glucose metabolism, with more prominent PIB binding and less FDG uptake in the parietal cortex of younger patients. Functional connectivity as measured using the phase lag index on EEG was reduced in AD patients compared to controls, with the largest reduction in younger AD patients. Furthermore, we observed that compared to age-matched controls, younger patients had more widespread gray matter loss than older patients. In a direct comparison, younger patients showed more tissue loss than older patients in the precuneus. These differences are in agreement with the clinical presentation of younger AD patients, which is often characterized by prominent impairment in visuospatial functions, executive functions, and/or language. The effect of APOE genotype on these measures was independent of age-at-onset, and included increased frontal PIB binding in APOE negative patients and decreased parietal glucose metabolism in APOE positive patients, while we were not able to show an effect on pattern of atrophy. Conclusions: Age-at-onset seems to influence the pathway leading to clinical AD at all levels of the cascade of events. Former studies suggested that the effects were largely expressed downstream, but we now showed a subtle upstream effect on the distribution of amyloid. S2-02-02

NEUROPATHOLOGICAL EVIDENCE OF HETEROGENEITY

Dennis Dickson, Mayo Clinic, Jacksonville, Florida, United States. Background: Neurofibrillary tangles (NFT) and senile plaques are defining lesions of the neuropathology of Alzheimer’s disease (AD). NFT have a stereotypic distribution that is the basis of Braak NFT staging of AD. Medial temporal lobe structures (e.g., hippocampus) are vulnerable early, and this correlates with conversion of at-risk individuals to AD and with clinical progression of AD. It is also the substrate for amnestic symptoms of AD; however, non-amnestic presentations of AD are recognized, and these cases often do not fit the Braak staging scheme. Methods: We systematically addressed heterogeneity in AD with a classification scheme based upon NFT counts in cortex and hippocampus with thioflavin S fluorescent microscopy

(Murray et al, Lancet Neurol 2011). Results: We identified subsets of early onset AD with short disease duration and sparse NFT in the hippocampus (hippocampal sparing AD) and late onset AD with long disease duration and many NFT in medial temporal lobe (limbic predominant AD). The former, often had atypical clinical presentations, including frontal dementia and progressive aphasia. The latter had slowly progressive amnestic dementia that could be mistaken for hippocampal sclerosis of the elderly, which is increasingly recognized as a late life amnestic syndrome. In over half of AD cases, limbic pathology is associated with TDP-43 or a-synuclein deposition in the amygdala. These cases tend to have more severe clinical symptoms, but no distinctive clinical syndrome has been identified for AD with amygdala predominant TDP-43 or a-synuclein deposition. Cerebrovascular pathology also contributes to clinical heterogeneity in AD. One particular form, cerebral amyloid angiopathy (CAA), is pathogenically linked to fundamental processes that cause AD, yet CAA is not present in all AD cases and in only a subset is it associated with overt clinical signs, often due to diffuse white matter pathology or cortical microhemorrhages. Conclusions: Recognition of heterogeneity of AD is important in clinical studies, since some cases will not be recognized as having AD and in other cases, the non-AD aspects of the disease process (including cerebrovascular lesions, as well as TDP-43 and a-synuclein deposition) may obscure response to future disease modifying therapies targeted at the fundamental AD lesions, senile plaques and NFT. S2-02-03

METRICS OF BRAIN NETWORK BREAKDOWN IN VARIANT SYNDROMES OF ALZHEIMER’S DISEASE

Jason Warren, University College London, London, United Kingdom. Background: Atypical phenotypes of Alzheimer’s disease (AD) are of considerable clinical and neurobiological interest. Clinically, such variant syndromes present major challenges for diagnosis and disease monitoring. Neurobiologically, they illustrate the problem of phenotypic diversity underpinned by a common histopathological substrate. This problem is particularly acute given current interest in identifying signatures of tissue pathology in AD and other neurodegenerative diseases and recent proposals that neurodegenerative brain damage reflects a coherent profile of neural network disintegration. Methods: Here I review the most important variant AD phenotypes and their neuroanatomical associations, focusing on the syndromes of posterior cortical atrophy and logopenic progressive aphasia and metrics that can capture distributed change at the level of large-scale brain networks. Results: The major AD phenotypes show separable but overlapping network-level signatures. The balance of evidence suggests a core profile of network involvement linked to AD pathology: this profile is importantly modulated by incompletely understood genetic and phenotypic modifiers, including factors that remain to be identified. Conclusions: Variant AD syndromes can be reconciled with the emerging network paradigm of neurodegenerative disease, with important clinical and neurobiological implications in the era of disease-modification trials. S2-02-04

AMYLOID BURDEN IN EARLY-ONSET VERSUS LATE-ONSET ALZHEIMER’S DISEASE: COMPARISON OF TWO EXTREMES

Hanna Cho, Sang Won Seo, Jung-Hyun Kim, Young Noh, Geon Ha Kim, Ji Soo Shin, Duk L. Na, Samsung Medical Center, Seoul, South Korea. Background: Patients with early-onset Alzheimer’s disease (EOAD) show more rapid progression, more generalized cognitive deficits and greater cortical atrophy and hypometabolism compared to patients with late-onset Alzheimer’s disease (LOAD) at a similar disease stage. The purpose of this study was to compare the distribution and burden of fibrillar amyloid-ß between EOAD and LOAD in the two extremes classification. Methods: We evaluated 68 patients with AD (61 with PiB-positive (PiB+) and 7 with PiBnegative (PiB-)) who underwent brain MRI, Pittsburg compound-B (PiB) PET and detailed neuropsychological tests. Sixty-one patients with PiB+ AD were divided according to the age at onset: Seventeen patients belonged to EOAD group (age onset