- Email: [email protected]
COMPARISON OF FOUR NEW CONSENSUS CRITERIA AGAINST THE 1984 NINCDS-ARDRA CRITERIA FOR ALZHEIMER'S DISEASE
Poster Presentations: P4 from 50 to 90 years old. This research was performed as part of a nationwide multicenter cohort called the CREDOS study. Twentynine subjects with SMI progressed to MCI or Alzheimer’s disease (AD) and the others (n¼100) did not progress. We compared baseline demographics, blood chemistry and neuropsychological tests results between the two groups and assessed predictors and the hazard ratio (HR) for the progression. Results: Follow up durations were ranged from 0.5 to 4.7 years. Median time to event was 3.64 years. Age, apolipoprotein E4 (APOE4) incidence, baseline Mini-Mental State Examination (MMSE) score, memory scores, geriatric depression scale (GDS) scores, Boston naming test, Rey complex figure copy/ recall and stroop test scores were different between groups. Old age, abnormal recall scores in MMSE, existence of APOE4 allele and lower verbal memory delayed recall scores were the most potent predictors related with the progression and the sum of the 4 predictors explained better for the progression. Conclusions: Subjects with SMI who progressed to MCI/ AD showed different baseline characteristics and neuropsychological tests results. Old age, worse baseline memory scores and APOE4 allele existence were related with the progression of SMI and combining them might be better to predict the progression. How to better coordinate the relative contributions of each predictor deserves further investigation.
P4-095
COMPARISON OF FOUR NEW CONSENSUS CRITERIA AGAINST THE 1984 NINCDS-ARDRA CRITERIA FOR ALZHEIMER’S DISEASE
Benjamin Lam1, Alexandra Kim1, Kie Honjo1, Isabel Wai Shan Lam1, Donald Stuss2, Mario Masellis1, Sandra Black3, 1Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; 2Ontario Brain Institute, Toronto, Ontario, Canada; 3Sunnybrook Research Institute, Toronto, Ontario, Canada. Contact e-mail: [email protected] Background: Diagnosis of Alzheimer’s disease (AD) has undergone significant revision, largely in response to advances in biomarker research and the understanding of AD’s syndromic complexity. The new criteria include: (1) International Working Group (IWG; Dubois 2007 and 2010), (2) International Classification of Disease (ICD-10; WHO 2010), (3) National Institute on Aging - Alzheimer’s Association (NIA-AA; McKhann 2011), and (4) DSM-5 (APA 2013). These differ in requirements for memory impairment, functional decline, biomarkers, and allowance for disease subtypes and mixed pathologies (Visser 2012). Comprehensive, systematic comparison in a group of well-characterized AD subjects remains to be done. Methods: Clinical history and imaging for 101 individuals from the Sunnybrook Dementia Study who met the 1984 NINCDS-ARDRA criteria (McKhann 1984), for probable AD were reviewed, applying the new criteria. Tc 99 -SPECT was used instead of FDG-PET for the NIA-AA and IWG criteria. Results: The NIA-AA and NINCDS-ARDRA criteria had excellent agreement, with 90% (n¼91) of those meeting the original 1984 McKhann criteria also satisfying the revised NIA-AA criteria. Among those that did not, 7 had insufficient functional decline to fulfill dementia criteria, and would be classified as MCI. By contrast, 47% (n¼47) of those meeting the 1984 McKhann criteria failed to meet the IWG criteria, similar to the results from a prior study comparing it to the ICD-10/DSMIV(Oksengard 2010). This may reflect the IWG’s strict requirement for biomarkers and predominantly amnestic course, and disallowance of co-pathology. Indeed, all atypical individuals from our cohort and those with mild-to-moderate white matter disease were rejected. Similarly, only 44% (n¼44) of those meeting the 1984 McKhann criteria met the ICD-10 criteria, likely reflecting construct differences , namely, ICD-10’s unique requirements for functional impairment and behavioural symptoms. 85% (n¼86) of those meeting the 1984 McKhann also met the DSM-V. Both allow for non-amnestic presentations and are largely based on a similar combination of cognitive and functional factors. Conclusions: Differences in
P819
syndrome construct (including functional decline), biomarker use, and allowance for co-pathology within criteria significantly affect the diagnostic classification of individuals with dementia. Going forward, such differences merit careful validation to ensure that criteria accurately and meaningfully reflect disease. P4-096
LATENT ANALYSIS OF EXTRAPYRAMIDAL SIGNS IN ALZHEIMER’S DISEASE IDENTIFIES DISTINCT DISEASE EXPRESSIONS
Giuseppe Tosto1, Sarah E. Monsell2, Walter Kukull2, Richard Mayeux3, 1 Columbia University, New York, New York, United States; 2National Alzheimer’s Coordinating Center, Seattle, Washington, United States; 3 Columbia University, New York, New York, United States. Contact e-mail: [email protected] Background: Patients with Alzheimer’s Disease (AD) can develop additional features such as extrapyramidal signs (EPS), a core manifestation of related forms of dementia, Dementia with Lewy Bodies (DLB) and Parkinson’s disease (PD). There is also neuropathological overlap between these entities: both Lewy bodies and amyloid pathology occur in all three conditions. Extrapyramidal signs can be present in all stages of AD, and their frequency increases as the disease progresses. Methods: We investigated clinical and neuropathological features underlying AD with EPS through a k-means latent analyses approach using longitudinal data from the National Alzheimer’s Coordinating Center (NACC) database (n¼7825). Three clusters were identified based on the progression of motor manifestations and compared in terms of cognitive and neuropsychiatric measures. A subset of these patients provided neuropathological data with primary NP diagnosis, Braak stage and Lewy Body assessment. Results: K-means latent analyses identified three distinct clusters of EPS progression: none/low (group A, n¼4726), medium (group B, n¼1629) and high (group C, n¼479) load of EPS. Compared to those with no or low EPS, those with medium or high EPS showed greater cognitive impairment and more frequent neuropsychiatric symptoms. Those with high EPS, compared to those with medium and none/low EPS, had significantly higher frequency of hallucinations (OR¼ 1.6, p<0.001; OR¼ 2.9, p<0.001 respectively) and severity (OR¼ 1.21, p¼ 0.002; OR¼ 1.6, p<0.001). Although Braak stages were similar among the subgroups, those with high EPS more often showed a Lewy Bodies neocortical/diffuse pattern (15% vs. 8% and 7%, p¼0.01) compared to those with no/low or medium EPS. Also, Lewy Body-pathology and AD-pathology co-expression significantly differed among the three clusters. Conclusions: Cluster analyses identified different subgroups of AD patients, showing distinct clinical and neuropathological features. Taken together the analyses confirmed the clinical heterogeneity of AD and suggested multiples underlying etiologies.
P4-097
FRAILTY TRANSITIONS OVER 6 MONTHS IN RELATION TO COGNITIVE STATUS IN COMMUNITY-DWELLING OLDER ADULTS IN A TERTIARY MEMORY CLINIC SETTING
Mei Sian Chong, Laura Tay, Peng Chew Mark Chan, Wee Shiong Lim, Ruijing Ye, Yew Yoong Ding, Tan Tock Seng Hospital, Singapore, Singapore. Contact e-mail: [email protected] Background: Frailty and cognitive impairment are seemingly distinct syndromes, but have shared vulnerability to stress in older adults, resulting in poorer health outcomes. Frailty transitions in relation to cognitive status have not yet been well studied. Methods: We studied MCI, mild and moderate AD subjects and obtained data on demographics, comorbidities, socioeconomic factors, physical activity level, lifestyle activities, cognition-related, nutritional and neuroimaging measures, functional status, muscle mass measurements, Vitamin D level, APOE status and physical performance measures. Frailty was classified at baseline and at 6 months
P4-095
COMPARISON OF FOUR NEW CONSENSUS CRITERIA AGAINST THE 1984 NINCDS-ARDRA CRITERIA FOR ALZHEIMER’S DISEASE
Benjamin Lam1, Alexandra Kim1, Kie Honjo1, Isabel Wai Shan Lam1, Donald Stuss2, Mario Masellis1, Sandra Black3, 1Sunnybrook Health Sciences Centre, Toronto, Ontario, Canada; 2Ontario Brain Institute, Toronto, Ontario, Canada; 3Sunnybrook Research Institute, Toronto, Ontario, Canada. Contact e-mail: [email protected] Background: Diagnosis of Alzheimer’s disease (AD) has undergone significant revision, largely in response to advances in biomarker research and the understanding of AD’s syndromic complexity. The new criteria include: (1) International Working Group (IWG; Dubois 2007 and 2010), (2) International Classification of Disease (ICD-10; WHO 2010), (3) National Institute on Aging - Alzheimer’s Association (NIA-AA; McKhann 2011), and (4) DSM-5 (APA 2013). These differ in requirements for memory impairment, functional decline, biomarkers, and allowance for disease subtypes and mixed pathologies (Visser 2012). Comprehensive, systematic comparison in a group of well-characterized AD subjects remains to be done. Methods: Clinical history and imaging for 101 individuals from the Sunnybrook Dementia Study who met the 1984 NINCDS-ARDRA criteria (McKhann 1984), for probable AD were reviewed, applying the new criteria. Tc 99 -SPECT was used instead of FDG-PET for the NIA-AA and IWG criteria. Results: The NIA-AA and NINCDS-ARDRA criteria had excellent agreement, with 90% (n¼91) of those meeting the original 1984 McKhann criteria also satisfying the revised NIA-AA criteria. Among those that did not, 7 had insufficient functional decline to fulfill dementia criteria, and would be classified as MCI. By contrast, 47% (n¼47) of those meeting the 1984 McKhann criteria failed to meet the IWG criteria, similar to the results from a prior study comparing it to the ICD-10/DSMIV(Oksengard 2010). This may reflect the IWG’s strict requirement for biomarkers and predominantly amnestic course, and disallowance of co-pathology. Indeed, all atypical individuals from our cohort and those with mild-to-moderate white matter disease were rejected. Similarly, only 44% (n¼44) of those meeting the 1984 McKhann criteria met the ICD-10 criteria, likely reflecting construct differences , namely, ICD-10’s unique requirements for functional impairment and behavioural symptoms. 85% (n¼86) of those meeting the 1984 McKhann also met the DSM-V. Both allow for non-amnestic presentations and are largely based on a similar combination of cognitive and functional factors. Conclusions: Differences in
P819
syndrome construct (including functional decline), biomarker use, and allowance for co-pathology within criteria significantly affect the diagnostic classification of individuals with dementia. Going forward, such differences merit careful validation to ensure that criteria accurately and meaningfully reflect disease. P4-096
LATENT ANALYSIS OF EXTRAPYRAMIDAL SIGNS IN ALZHEIMER’S DISEASE IDENTIFIES DISTINCT DISEASE EXPRESSIONS
Giuseppe Tosto1, Sarah E. Monsell2, Walter Kukull2, Richard Mayeux3, 1 Columbia University, New York, New York, United States; 2National Alzheimer’s Coordinating Center, Seattle, Washington, United States; 3 Columbia University, New York, New York, United States. Contact e-mail: [email protected] Background: Patients with Alzheimer’s Disease (AD) can develop additional features such as extrapyramidal signs (EPS), a core manifestation of related forms of dementia, Dementia with Lewy Bodies (DLB) and Parkinson’s disease (PD). There is also neuropathological overlap between these entities: both Lewy bodies and amyloid pathology occur in all three conditions. Extrapyramidal signs can be present in all stages of AD, and their frequency increases as the disease progresses. Methods: We investigated clinical and neuropathological features underlying AD with EPS through a k-means latent analyses approach using longitudinal data from the National Alzheimer’s Coordinating Center (NACC) database (n¼7825). Three clusters were identified based on the progression of motor manifestations and compared in terms of cognitive and neuropsychiatric measures. A subset of these patients provided neuropathological data with primary NP diagnosis, Braak stage and Lewy Body assessment. Results: K-means latent analyses identified three distinct clusters of EPS progression: none/low (group A, n¼4726), medium (group B, n¼1629) and high (group C, n¼479) load of EPS. Compared to those with no or low EPS, those with medium or high EPS showed greater cognitive impairment and more frequent neuropsychiatric symptoms. Those with high EPS, compared to those with medium and none/low EPS, had significantly higher frequency of hallucinations (OR¼ 1.6, p<0.001; OR¼ 2.9, p<0.001 respectively) and severity (OR¼ 1.21, p¼ 0.002; OR¼ 1.6, p<0.001). Although Braak stages were similar among the subgroups, those with high EPS more often showed a Lewy Bodies neocortical/diffuse pattern (15% vs. 8% and 7%, p¼0.01) compared to those with no/low or medium EPS. Also, Lewy Body-pathology and AD-pathology co-expression significantly differed among the three clusters. Conclusions: Cluster analyses identified different subgroups of AD patients, showing distinct clinical and neuropathological features. Taken together the analyses confirmed the clinical heterogeneity of AD and suggested multiples underlying etiologies.
P4-097
FRAILTY TRANSITIONS OVER 6 MONTHS IN RELATION TO COGNITIVE STATUS IN COMMUNITY-DWELLING OLDER ADULTS IN A TERTIARY MEMORY CLINIC SETTING
Mei Sian Chong, Laura Tay, Peng Chew Mark Chan, Wee Shiong Lim, Ruijing Ye, Yew Yoong Ding, Tan Tock Seng Hospital, Singapore, Singapore. Contact e-mail: [email protected] Background: Frailty and cognitive impairment are seemingly distinct syndromes, but have shared vulnerability to stress in older adults, resulting in poorer health outcomes. Frailty transitions in relation to cognitive status have not yet been well studied. Methods: We studied MCI, mild and moderate AD subjects and obtained data on demographics, comorbidities, socioeconomic factors, physical activity level, lifestyle activities, cognition-related, nutritional and neuroimaging measures, functional status, muscle mass measurements, Vitamin D level, APOE status and physical performance measures. Frailty was classified at baseline and at 6 months