Prevalence and diagnostic procedures in early-onset dementia in tertiary referral center patients in denmark, sweden, and the netherlands

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Podium Presentations: Tuesday, July 21, 2015

neuropsychiatric symptoms, apathy was significantly higher (p¼0.001) in EOD, whereas motor disturbances (p¼0.03) & night time behaviours (p<0.001) was more in LOD. Similar results were observed for AD, apathy, anxiety and depression was more in early-onset AD, whereas agitation, motor disturbances and night time behaviours was higher in late-onset AD (p<0.05). We did not find significant differences between early and late-onset FTD. Regarding treatment history, more number of LOD (66%) compared to EOD (37%) were seeking help for the first time, however the mean duration of illness before seeking any professional help was similar in both groups (23-25 months). Conclusions: Presence of non-cognitive symptoms such as apathy differentiated the early from late onset group, though they were similar in co-morbidity, cognition and disease severity. The longer duration of illness at presentation in EOD could be probably due to the delay in diagnoses. Biological and genetic basis for the differences in non-cognitive aspects could be explored in future studies. O3-11-02

PREVALENCE AND DIAGNOSTIC PROCEDURES IN EARLY-ONSET DEMENTIA IN TERTIARY REFERRAL CENTER PATIENTS IN DENMARK, SWEDEN, AND THE NETHERLANDS

Elles Konijnenberg1, Seyed-Mohammad Fereshtehnejad2, Maria Eriksdotter2, Philip Scheltens1,3, Peter Johannsen4, Gunhild Waldemar4, Pieter Jelle Visser1,5, 1VU University Medical Center, Amsterdam, Netherlands; 2Karolinska Institutet, Stockholm, Sweden; 3 Neuroscience Campus Amsterdam, Amsterdam, Netherlands; 4Danish Dementia Research Centre, Rigshospitalet, Copenhagen University Hospital, Copenhagen, Denmark; 5Alzheimer Center Limburg, School for Mental Health and Neuroscience, Maastricht University, Maastricht, Netherlands. Contact e-mail: [email protected] Background: Specialized memory clinics may vary in type of subjects seen, diagnostic procedures applied, and pharmacological

treatment given. Denmark, Sweden, and the Netherlands are often compared, because of their similar socio-economic status and healthcare system. Aim of this study was to compare the prevalence of early-onset dementia (EOD), patient characteristics, diagnostic procedures and medication use between tertiary referral centers in Copenhagen, Stockholm and Amsterdam. Methods: Data from newly diagnosed dementia patients seen between 1 January 2007 and 31 December 2013 were obtained from Danish Dementia Registry (Rigshospitalet, Copenhagen), Swedish Dementia Registry (“SveDem”, Huddinge Hospital, Stockholm), and Amsterdam Dementia Cohort database (VU University Medical Center). We included 4690 subjects, Copenhagen: 2019 (43%), Stockholm: 1350 (29%) and Amsterdam: 1321 (28%). EOD definition used: dementia diagnosis in patients  65 years. We compared patient characteristics, diagnostic procedures and medication use. Results: Prevalence of EOD in all dementia patients was lower in Stockholm and Copenhagen. Age at time of diagnosis was slightly lower in Copenhagen. In EOD patients in Amsterdam Alzheimer’s disease (AD), frontotemporal lobe dementia (FTD) and Lewy Body Dementia (DLB) were more common and vascular dementia (VaD) less common, see Table 1. In Stockholm more patients with mixed dementia were seen. Subjects in Amsterdam scored lower on MMSE. Time to diagnosis was shortest in Amsterdam. MMSE was less often performed in Copenhagen. CT was more often and MRI less often performed in Copenhagen than in Stockholm than in Amsterdam. Blood tests were more often performed in Amsterdam. Use of antidepressants and antipsychotics was more common in Copenhagen. Cholinesterase inhibitors were more often used in Stockholm, while memantine was more often used in Copenhagen and Stockholm. Conclusions: Between tertiary referral centers in Copenhagen, Stockholm and Amsterdam we noted differences in prevalence of EOD, diagnosis, procedures and medication use. Less MMSE performed

Table 1 Results of comparison EOD patients in Stockholm, Copenhagen, and Amsterdam.

Patient characteristics (EOD) Gender, male (n, %) Prevalence EOD (n, %) Age at the time of diagnosis in years, mean (SD) Diagnosis Alzheimer’s Disease (AD) Frontotemporal Lobe Dementia (FTD) Dementia with Lewy Bodies (DLB) Vascular Dementia (VaD) Mixed Dementia Other neurodegenerative MMSE score, mean (SD) Diagnostic procedures Time to diagnosis, days, mean (SD) MMSE performed (yes, %) CT performed (yes, %) MRI performed (yes, %) Blood tests (yes, %) Medication use Antidepressants (yes, %) Antipsychotics (yes, %) Cholinesterase inhibitors (yes, %) Mem antin (yes, %) *Differs from both other sites **Differs from Stockholm only ^ Differs from Copenhagen only ## Differs from Amsterdam only

Copenhagen

Stockholm

Amsterdam

223 (54%) 410 (20%) 58.6 (6.2)** (p<0.01)

130 (47%) 274 (20%) 59.9 (4.4)

338 (49%) 631 (48%)* (p<0.01) 59.4 (4.9)

44% 11% 4% 10% 1% 19% 22.1 (6.4)##

49% 8% 2% 12% 15%* 14% 21.9 (5.3)

66%* 18%* 6%** 3%* 0% 8%* 21.1 (5.3)

61 (54) 89%* (p<0.01) 67%* (p<0.01) 44%* (p<0.01) 91%

94 (108) 96% 48%* (p<0.01) 72%* (p<0.01) 95%

5 (7)* (p<0.01) 98% 5% 79% 100%* (p<0.01)

33%* (p<0.01) 8% 43% 2%

21% 5% 53.4% ^ (p<0.05) 5%

21% 4% 46.3% 0%* (p<0.01)

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

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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.