- Email: [email protected]
ALZHEIMER DISEASE (AD) AND MULTIPLE SYSTEM ATROPHY (MSA) DIAGNOSED CLINICALLY AS AD WITH GAIT ABNORMALITY
Poster Presentations: Monday, July 17, 2017
78.4% (95% CI 76.3% – 80.3%) had neuropathology indicative of AD. At last visit this increased to 81.3% (95% CI: 78.8% - 83.7). There was no significant difference in accuracy of clinical diagnosis when data was analyzed for race, gender, education level, or time followed. Patients with ApoE genotype of ε4, ε4 were most likely to have matching clinical and neuropathological data (83.3%, p ¼ 0.0003) as were those with higher Geriatric Depression Scores (p ¼ 0.012). Lewy body dementia (LBD) (29%) and frontotemporal lobar degeneration (FTLD) (19%) were the most common neuropathological diagnoses in those that were misdiagnosed as clinically having AD. Conclusions: The misdiagnosis rate of AD can be as high as 20%, even by the most experienced clinicians. With factors such as race, gender, education level, and time followed not having a significant effect, more studies are needed to examine what factors do contribute to this misdiagnosis. Reasons for the higher rate of misdiagnosis between AD and LBD also warrant further study.
P2-431
ALZHEIMER DISEASE (AD) AND MULTIPLE SYSTEM ATROPHY (MSA) DIAGNOSED CLINICALLY AS AD WITH GAIT ABNORMALITY
Kathy Newell1, Anne Arthur2, University of Kansas Alzheimer Disease Center, 1University of Kansas Medical School, Kansas City, KS, USA; 2 University of Kansas Medical Center, Kansas City, KS, USA. Contact e-mail: [email protected] Background: Cognitive decline and cerebellar ataxia are not frequently observed as presenting signs in AD. When present together, these symptoms may suggest a dominantly inherited AD variant; however, they are not seen in late onset AD. We have studied a 64 year-old woman who presented with both memory loss and cerebellar signs at the neurologic evaluation. Methods: Clinical and neuropathologic investigations were carried out. Formalin-fixed paraffin-embedded brain sections were studied using histological methods including Luxol fast blue-hematoxylin and eosin (LHE) and Thioflavin-S. For immunohistochemistry, bamyloid, tau, a-synuclein, and pTDP43 antibodies were used. Results: At age 66y, the patient had difficulty with ambulation and balance. A progressively unsteady gait caused frequent falls. MMSE scores were 20/30 at 67y; 10/30 at 68y. By 68y, significant difficulties in activities of daily living, conversation, and ambulation were present. Speech was reduced, soft, and slow. Movements during sleep were noted. She died after 7 years of progressive illness at age 71y. The neuropathologic study revealed moderate to severe atrophy of the frontotemporal lobes, mild atrophy of the parietal-occipital lobes, and moderate atrophy of the amygdala and hippocampus. The brain stem showed marked atrophy of the basis pontis. Pigmentation of the substantia nigra and locus coeruleus was reduced. The inferior olives had a yellow discoloration. The cerebellum was severely atrophic with tan discoloration of the white matter. Microscopically, b-amyloid immunopositive plaques as well as intracytoplasmic tau deposits were seen throughout the cerebral cortex and hippocampus (Thal phase V, Braak stage V). TDP43-positive aggregates were present in the amygdala and entorhinal cortex. In the basis pontis, cerebellum, and inferior olivary nucleus, myelinated fibers were reduced in number. In the cerebral hemispheres, brain stem, and cerebellum, Papp-Lantos inclusions were seen in white matter oligodendroglia, confirmed with a-synuclein, indicative of MSA, an a-synucleinopathy. The microscopic study supported the diagnosis of two coexisting disorders: AD and
P801
MSA-olivopontocerebellar atrophy (OPCA). Conclusions: The coexistence of AD and OPCA correlates with the clinical impression of AD with a progressive gait disturbance. This case provides the opportunity to study the interactions of multiple protein aggregates involving neurons and glia in multiple brain regions. Grant: P30AG035982.
P2-432
IMPAIRMENTS OF MOTOR FUNCTION AS CORRELATES OR HARBINGERS OF DEMENTIA IN THE HONOLULU-ASIA AGING STUDY
Lon R. White1,2,3, Catherine Liu4, Kathleen Montine5, Lenore J. Launer6, Steven D. Edland7, Thomas J. Montine8, 1National Institute on Aging, NIH, Bethesda, MD, USA; 2Pacific Health Research and Education Institute, Honolulu, HI, USA; 3John A Burns School of Medicine, Honolulu, HI, USA; 4 Pacific Health Research and Education Institute, Honolulu, HI, USA; 5 Stanford University, Stanford, CA, USA; 6National Institute on Aging, Bethesda, MD, USA; 7University of California, San Diego, San Diego, CA, USA; 8Stanford University School of Medicine, Stanford, CA, USA. Contact e-mail: [email protected] Background: The well recognized, frequent co-existence of physical impairment and dementia in aging persons has suggested that motor impairments might operate as predictors of cognitive decline. Conversely, many persons with Alzheimer’s disease retain normal motor competence, including abilities to dance, play musical instruments, or carry out other complex physical activities. Given the diverse pathologic processes and brain lesions involved in dementia, sequential or concurrent development of motor and cognitive impairment might represent distinct types and regional distributions of neuropathologic abnormality. Methods: Among 3734 Japanese-American men who participated in the baseline HAAS exam (1991-93), 3705 received baseline assessments of cognition (CASI), timed walk, grip strength, chair stands, and tandem stand balance. These were repeated at subsequent examination cycles. Comprehensive brain autopsies were completed on 774 decedent participants in whom these assessments were done. Results: At baseline, 2 or more motor impairments were identified in more than half of those with severe cognitive impairment (CASI<60), in 12% of those with moderate cognitive impairment, and in 4% of those with normal or marginal CASI scores. In multivariate regression analyses the baseline associations of motor impairments with cognitive impairment became statistically insignificant upon controlling for age and ApoE ἐ 4 zygosity. Additional analyses were conducted to determine if “new” motor impairments would predict the subsequent development of cognitive impairment. This was not supported by longitudinal assessments over the two decade course of the study, even though concurrent motor and cognitive impairments were common. Among autopsied decedents, the neuropathologic abnormalities observed in those who had both motor and cognitive impairment before death included not only the neocortical and hippocampal abnormalities previously linked to dementia, but also neuronal loss and gliosis in the brainstem, as well as marginal abnormalities involving the striata and cerebellum. Conclusions: While the development of motor impairment does not appear to be an important harbinger of imminent cognitive impairment, extensions of the pathologic processes responsible for dementia into brain regions responsible for motor control may contribute to the concurrent development of motor and cognitive impairment.
78.4% (95% CI 76.3% – 80.3%) had neuropathology indicative of AD. At last visit this increased to 81.3% (95% CI: 78.8% - 83.7). There was no significant difference in accuracy of clinical diagnosis when data was analyzed for race, gender, education level, or time followed. Patients with ApoE genotype of ε4, ε4 were most likely to have matching clinical and neuropathological data (83.3%, p ¼ 0.0003) as were those with higher Geriatric Depression Scores (p ¼ 0.012). Lewy body dementia (LBD) (29%) and frontotemporal lobar degeneration (FTLD) (19%) were the most common neuropathological diagnoses in those that were misdiagnosed as clinically having AD. Conclusions: The misdiagnosis rate of AD can be as high as 20%, even by the most experienced clinicians. With factors such as race, gender, education level, and time followed not having a significant effect, more studies are needed to examine what factors do contribute to this misdiagnosis. Reasons for the higher rate of misdiagnosis between AD and LBD also warrant further study.
P2-431
ALZHEIMER DISEASE (AD) AND MULTIPLE SYSTEM ATROPHY (MSA) DIAGNOSED CLINICALLY AS AD WITH GAIT ABNORMALITY
Kathy Newell1, Anne Arthur2, University of Kansas Alzheimer Disease Center, 1University of Kansas Medical School, Kansas City, KS, USA; 2 University of Kansas Medical Center, Kansas City, KS, USA. Contact e-mail: [email protected] Background: Cognitive decline and cerebellar ataxia are not frequently observed as presenting signs in AD. When present together, these symptoms may suggest a dominantly inherited AD variant; however, they are not seen in late onset AD. We have studied a 64 year-old woman who presented with both memory loss and cerebellar signs at the neurologic evaluation. Methods: Clinical and neuropathologic investigations were carried out. Formalin-fixed paraffin-embedded brain sections were studied using histological methods including Luxol fast blue-hematoxylin and eosin (LHE) and Thioflavin-S. For immunohistochemistry, bamyloid, tau, a-synuclein, and pTDP43 antibodies were used. Results: At age 66y, the patient had difficulty with ambulation and balance. A progressively unsteady gait caused frequent falls. MMSE scores were 20/30 at 67y; 10/30 at 68y. By 68y, significant difficulties in activities of daily living, conversation, and ambulation were present. Speech was reduced, soft, and slow. Movements during sleep were noted. She died after 7 years of progressive illness at age 71y. The neuropathologic study revealed moderate to severe atrophy of the frontotemporal lobes, mild atrophy of the parietal-occipital lobes, and moderate atrophy of the amygdala and hippocampus. The brain stem showed marked atrophy of the basis pontis. Pigmentation of the substantia nigra and locus coeruleus was reduced. The inferior olives had a yellow discoloration. The cerebellum was severely atrophic with tan discoloration of the white matter. Microscopically, b-amyloid immunopositive plaques as well as intracytoplasmic tau deposits were seen throughout the cerebral cortex and hippocampus (Thal phase V, Braak stage V). TDP43-positive aggregates were present in the amygdala and entorhinal cortex. In the basis pontis, cerebellum, and inferior olivary nucleus, myelinated fibers were reduced in number. In the cerebral hemispheres, brain stem, and cerebellum, Papp-Lantos inclusions were seen in white matter oligodendroglia, confirmed with a-synuclein, indicative of MSA, an a-synucleinopathy. The microscopic study supported the diagnosis of two coexisting disorders: AD and
P801
MSA-olivopontocerebellar atrophy (OPCA). Conclusions: The coexistence of AD and OPCA correlates with the clinical impression of AD with a progressive gait disturbance. This case provides the opportunity to study the interactions of multiple protein aggregates involving neurons and glia in multiple brain regions. Grant: P30AG035982.
P2-432
IMPAIRMENTS OF MOTOR FUNCTION AS CORRELATES OR HARBINGERS OF DEMENTIA IN THE HONOLULU-ASIA AGING STUDY
Lon R. White1,2,3, Catherine Liu4, Kathleen Montine5, Lenore J. Launer6, Steven D. Edland7, Thomas J. Montine8, 1National Institute on Aging, NIH, Bethesda, MD, USA; 2Pacific Health Research and Education Institute, Honolulu, HI, USA; 3John A Burns School of Medicine, Honolulu, HI, USA; 4 Pacific Health Research and Education Institute, Honolulu, HI, USA; 5 Stanford University, Stanford, CA, USA; 6National Institute on Aging, Bethesda, MD, USA; 7University of California, San Diego, San Diego, CA, USA; 8Stanford University School of Medicine, Stanford, CA, USA. Contact e-mail: [email protected] Background: The well recognized, frequent co-existence of physical impairment and dementia in aging persons has suggested that motor impairments might operate as predictors of cognitive decline. Conversely, many persons with Alzheimer’s disease retain normal motor competence, including abilities to dance, play musical instruments, or carry out other complex physical activities. Given the diverse pathologic processes and brain lesions involved in dementia, sequential or concurrent development of motor and cognitive impairment might represent distinct types and regional distributions of neuropathologic abnormality. Methods: Among 3734 Japanese-American men who participated in the baseline HAAS exam (1991-93), 3705 received baseline assessments of cognition (CASI), timed walk, grip strength, chair stands, and tandem stand balance. These were repeated at subsequent examination cycles. Comprehensive brain autopsies were completed on 774 decedent participants in whom these assessments were done. Results: At baseline, 2 or more motor impairments were identified in more than half of those with severe cognitive impairment (CASI<60), in 12% of those with moderate cognitive impairment, and in 4% of those with normal or marginal CASI scores. In multivariate regression analyses the baseline associations of motor impairments with cognitive impairment became statistically insignificant upon controlling for age and ApoE ἐ 4 zygosity. Additional analyses were conducted to determine if “new” motor impairments would predict the subsequent development of cognitive impairment. This was not supported by longitudinal assessments over the two decade course of the study, even though concurrent motor and cognitive impairments were common. Among autopsied decedents, the neuropathologic abnormalities observed in those who had both motor and cognitive impairment before death included not only the neocortical and hippocampal abnormalities previously linked to dementia, but also neuronal loss and gliosis in the brainstem, as well as marginal abnormalities involving the striata and cerebellum. Conclusions: While the development of motor impairment does not appear to be an important harbinger of imminent cognitive impairment, extensions of the pathologic processes responsible for dementia into brain regions responsible for motor control may contribute to the concurrent development of motor and cognitive impairment.