- Email: [email protected]
Early- versus late-onset subcortical vascular cognitive impairment
Podium Presentations: Tuesday, July 21, 2015
in Copenhagen could be due to more Down syndrome or non-Danish speaking patients. Short time to diagnosis in Amsterdam could be caused by a one day pre-orderered dementia work-up track including neuropsychological testing and imaging. These results reflect differences in referral pattern, application of diagnostic criteria, national guidelines, and local best practices. O3-11-03
EARLY- VERSUS LATE-ONSET SUBCORTICAL VASCULAR COGNITIVE IMPAIRMENT
Young Kyoung Jang1, Na Yeon Jung1, Yeo Jin Kim1, Yearn Seong Cheo1, Kyung Han Lee1, Sung Tae Kim1, Jae Seoung Kim2, Jae-Hong Lee2, Jong Min Lee3, Jin-Ju Yang3, Changsoo Kim4, Juhee Chin5, Sang Won Seo1, Duk L. Na1, Hee Jin Kim1, 1Samsung Medical Center, Seoul, South Korea; 2 Asan Medical Center, Seoul, South Korea; 3Hanyang University, Seoul, South Korea; 4Yonsei Medical Center, Seoul, South Korea; 5Neuroscience Center, Samsung Medical Center, Seoul, South Korea. Contact e-mail: [email protected] Background: Early onset Alzheimer’s disease and early onset fronto-
temporal dementia have been largely studied, while little attention was paid to early onset subcortical vascular cognitive impairment (EOSVCI). The aim of this study was to evaluate the differences between EOSVCI and late onset SVCI (LOSVCI) in terms of small vessel disease burden, amyloid burden, brain atrophy pattern, and cognitive dysfunction. Methods: We prospectively recruited 137 patients from a single referral center. Patients were divided into EOSVCI (n¼30, onset age <65 years) and LOSVCI (n¼107, onset age 65 years). All patients underwent brain MRI, PiB-PET and detailed neuropsychological testing. Cortical thickness and volume of subcortical structures were analyzed. Results: The educational level or severity of cognitive impairment did not differ between EOSVCI and LOSVCI patients. History of stroke and obesity were more prevalent in EOSVCI patients. EOSVCI patients tend to have higher number of lacune and had lower PiB-retention-ratio than LOSVCI patients. Atrophy in temporal and occipital cortex, amygdala, and hippocampus were more severe in LOSVCI, while pallidal atrophy was more severe in EOSVCI. The neuropsychological test showed that frontal-executive dysfunction was more prominant in EOSVCI patients while memory dyfunction was more prominent in LOSVCI patients. Conclusions: EOSVCI patients had more vascular related factors while LOSVCI patients exhibited more Alzheimer’s disease related characteristics. This suggests that cognitive dysfunction in LOSVCI is partially driven by aging related factors such as amyloid burden, whereas in EOSVCI, more extensive amount of vascular factors are necessary to reach the same stage of cognitive impairment. O3-11-04
LEARNING DISABILITY STATUS WITHIN THE POSTERIOR CORTICAL ATROPHY SYNDROME
Zachary A. Miller, Lynne M. Rosenberg, Melanie Stephens, Maria Luisa Mandelli, Gil D. Rabinovici, Bruce L. Miller, Maria Luisa Gorno Tempini, University of California San Francisco, San Francisco, CA, USA. Contact e-mail: [email protected] Background: Previously, we have shown that neurodevelopmental factors like LD and hand preference differentially distribute across variants of primary progressive (PPA). Compared to the general population, we observed an increased rate of non-right-handedness in semantic variant PPA and developmental dyslexia in logopenic variant PPA (lvPPA). We hypothesized that the presence of language-based LD in a large subset of our lvPPA cohort reflected unique underlying disease susceptibility of the language network to neurodegenerative disease. Given this, we hypothesized that
P245
non-language-based learning disabilities might provide similar disease susceptibility in their respective networks and investigated the prevalence and quality of LD in Posterior Cortical Atrophy (PCA), also known as the visual variant of Alzheimer’s disease. Methods: We retrospectively screened the UCSF Memory and Aging Center’s PCA cohort (n¼95) for history of LD. Results: Our PCA cohort displayed greater than the 10% expected amount of LD for the general population, 18% [(17/94) p ¼ 0.005]. More than half of the LD within PCA was non-language-based, mathematical and/or visuospatial (11/17). Mathematical LD is estimated to occur at rates of up to 6% in the general population. Compared to general population rates, these non-language-based LDs occurred at a significantly higher rate in our PCA cohort, 12% [(11/94) p¼ 0.03]. Conclusions: Non-language-based, mathematical and/or visuospatial, LD appear to be overrepresented in PCA. This pattern of association between modality specific LD and focal neurodegenerative disease presentation parallels our prior findings reported in lvPPA. Together, our findings suggest that underlying neurodevelopmental differences in brain structure influence the phenotypic presentation of select neurodegenerative disease. These observations offer tremendous opportunities towards disease prevention as neurodevelopmental differences usually present in grade school, more than 50 years before the typical onset of these associated neurodegenerative syndromes.
O3-11-05
GREATER WEIGHT CHANGE PER DECADE FROM MIDLIFE THROUGH LATE LIFE PREDICTS INCIDENT MCI
Rosebud O. Roberts, Mayo Clinic, Rochester, MN, USA. Contact e-mail: [email protected] Background: Unintentional weight loss has been associated with risk of dementia. Few large population-based studies have examined the association of weight change with risk of mild cognitive impairment (MCI). We aim to investigate the association of rate of weight change per decade with risk of MCI. Methods: Cognitively normal participants (n¼2,061; mean age, 78.8 years; 50.5% male) in the population-based prospective Mayo Clinic Study of Aging were clinically evaluated every 15 months for incident MCI. Weight and height at ages 70 or older were measured at each evaluation. Maximum adult weight and height in midlife (i.e. ages 40 to 65 years; mean, 59.7) were ascertained for each participant using a medical records linkage system. We investigated the association of weight change per decade (from midlife through late life) with risk of MCI using proportional hazards models with age as the time scale. Results: Over a mean (SD) follow-up of 4.4 (2.4) years, 578 participants developed incident MCI. The mean weight change per decade (in kilograms) was -1.8 (6.5) for persons with incident MCI cases vs. -1.2 (6.1) for persons who remained cognitively normal (p ¼ 0.015). Declining weight per decade was associated with an increased risk of MCI (beta (SE), -0.031 [0.007]; p <0.0001) after adjustment for sex and education. There was a sex difference showing a stronger association in men (beta, -0.04 [0.012], p ¼ 0.0002) than in women (beta, -0.022 [0.010]; p ¼ 0.026). Risk of MCI also increased with decline in body mass index per decade (-0.059 [0.019], p ¼ 0.002). Conclusions: The rate of weight change from midlife through late life predicts incident MCI and should be considered in risk stratification models for MCI. The stronger association in men may relate to the earlier onset of MCI in men observed in our previous studies.
in Copenhagen could be due to more Down syndrome or non-Danish speaking patients. Short time to diagnosis in Amsterdam could be caused by a one day pre-orderered dementia work-up track including neuropsychological testing and imaging. These results reflect differences in referral pattern, application of diagnostic criteria, national guidelines, and local best practices. O3-11-03
EARLY- VERSUS LATE-ONSET SUBCORTICAL VASCULAR COGNITIVE IMPAIRMENT
Young Kyoung Jang1, Na Yeon Jung1, Yeo Jin Kim1, Yearn Seong Cheo1, Kyung Han Lee1, Sung Tae Kim1, Jae Seoung Kim2, Jae-Hong Lee2, Jong Min Lee3, Jin-Ju Yang3, Changsoo Kim4, Juhee Chin5, Sang Won Seo1, Duk L. Na1, Hee Jin Kim1, 1Samsung Medical Center, Seoul, South Korea; 2 Asan Medical Center, Seoul, South Korea; 3Hanyang University, Seoul, South Korea; 4Yonsei Medical Center, Seoul, South Korea; 5Neuroscience Center, Samsung Medical Center, Seoul, South Korea. Contact e-mail: [email protected] Background: Early onset Alzheimer’s disease and early onset fronto-
temporal dementia have been largely studied, while little attention was paid to early onset subcortical vascular cognitive impairment (EOSVCI). The aim of this study was to evaluate the differences between EOSVCI and late onset SVCI (LOSVCI) in terms of small vessel disease burden, amyloid burden, brain atrophy pattern, and cognitive dysfunction. Methods: We prospectively recruited 137 patients from a single referral center. Patients were divided into EOSVCI (n¼30, onset age <65 years) and LOSVCI (n¼107, onset age 65 years). All patients underwent brain MRI, PiB-PET and detailed neuropsychological testing. Cortical thickness and volume of subcortical structures were analyzed. Results: The educational level or severity of cognitive impairment did not differ between EOSVCI and LOSVCI patients. History of stroke and obesity were more prevalent in EOSVCI patients. EOSVCI patients tend to have higher number of lacune and had lower PiB-retention-ratio than LOSVCI patients. Atrophy in temporal and occipital cortex, amygdala, and hippocampus were more severe in LOSVCI, while pallidal atrophy was more severe in EOSVCI. The neuropsychological test showed that frontal-executive dysfunction was more prominant in EOSVCI patients while memory dyfunction was more prominent in LOSVCI patients. Conclusions: EOSVCI patients had more vascular related factors while LOSVCI patients exhibited more Alzheimer’s disease related characteristics. This suggests that cognitive dysfunction in LOSVCI is partially driven by aging related factors such as amyloid burden, whereas in EOSVCI, more extensive amount of vascular factors are necessary to reach the same stage of cognitive impairment. O3-11-04
LEARNING DISABILITY STATUS WITHIN THE POSTERIOR CORTICAL ATROPHY SYNDROME
Zachary A. Miller, Lynne M. Rosenberg, Melanie Stephens, Maria Luisa Mandelli, Gil D. Rabinovici, Bruce L. Miller, Maria Luisa Gorno Tempini, University of California San Francisco, San Francisco, CA, USA. Contact e-mail: [email protected] Background: Previously, we have shown that neurodevelopmental factors like LD and hand preference differentially distribute across variants of primary progressive (PPA). Compared to the general population, we observed an increased rate of non-right-handedness in semantic variant PPA and developmental dyslexia in logopenic variant PPA (lvPPA). We hypothesized that the presence of language-based LD in a large subset of our lvPPA cohort reflected unique underlying disease susceptibility of the language network to neurodegenerative disease. Given this, we hypothesized that
P245
non-language-based learning disabilities might provide similar disease susceptibility in their respective networks and investigated the prevalence and quality of LD in Posterior Cortical Atrophy (PCA), also known as the visual variant of Alzheimer’s disease. Methods: We retrospectively screened the UCSF Memory and Aging Center’s PCA cohort (n¼95) for history of LD. Results: Our PCA cohort displayed greater than the 10% expected amount of LD for the general population, 18% [(17/94) p ¼ 0.005]. More than half of the LD within PCA was non-language-based, mathematical and/or visuospatial (11/17). Mathematical LD is estimated to occur at rates of up to 6% in the general population. Compared to general population rates, these non-language-based LDs occurred at a significantly higher rate in our PCA cohort, 12% [(11/94) p¼ 0.03]. Conclusions: Non-language-based, mathematical and/or visuospatial, LD appear to be overrepresented in PCA. This pattern of association between modality specific LD and focal neurodegenerative disease presentation parallels our prior findings reported in lvPPA. Together, our findings suggest that underlying neurodevelopmental differences in brain structure influence the phenotypic presentation of select neurodegenerative disease. These observations offer tremendous opportunities towards disease prevention as neurodevelopmental differences usually present in grade school, more than 50 years before the typical onset of these associated neurodegenerative syndromes.
O3-11-05
GREATER WEIGHT CHANGE PER DECADE FROM MIDLIFE THROUGH LATE LIFE PREDICTS INCIDENT MCI
Rosebud O. Roberts, Mayo Clinic, Rochester, MN, USA. Contact e-mail: [email protected] Background: Unintentional weight loss has been associated with risk of dementia. Few large population-based studies have examined the association of weight change with risk of mild cognitive impairment (MCI). We aim to investigate the association of rate of weight change per decade with risk of MCI. Methods: Cognitively normal participants (n¼2,061; mean age, 78.8 years; 50.5% male) in the population-based prospective Mayo Clinic Study of Aging were clinically evaluated every 15 months for incident MCI. Weight and height at ages 70 or older were measured at each evaluation. Maximum adult weight and height in midlife (i.e. ages 40 to 65 years; mean, 59.7) were ascertained for each participant using a medical records linkage system. We investigated the association of weight change per decade (from midlife through late life) with risk of MCI using proportional hazards models with age as the time scale. Results: Over a mean (SD) follow-up of 4.4 (2.4) years, 578 participants developed incident MCI. The mean weight change per decade (in kilograms) was -1.8 (6.5) for persons with incident MCI cases vs. -1.2 (6.1) for persons who remained cognitively normal (p ¼ 0.015). Declining weight per decade was associated with an increased risk of MCI (beta (SE), -0.031 [0.007]; p <0.0001) after adjustment for sex and education. There was a sex difference showing a stronger association in men (beta, -0.04 [0.012], p ¼ 0.0002) than in women (beta, -0.022 [0.010]; p ¼ 0.026). Risk of MCI also increased with decline in body mass index per decade (-0.059 [0.019], p ¼ 0.002). Conclusions: The rate of weight change from midlife through late life predicts incident MCI and should be considered in risk stratification models for MCI. The stronger association in men may relate to the earlier onset of MCI in men observed in our previous studies.