O2-01-02: Onset of Alzheimer's dementia occurs commonly without prior cognitive impairment: Results from the Alzheimer's disease anti-inflammatory prevention trial (ADAPT)

O2-01-02: Onset of Alzheimer's dementia occurs commonly without prior cognitive impairment: Results from the Alzheimer's disease anti-inflammatory prevention trial (ADAPT)

T130 Oral O2-01: Diagnosis and Clinical Course: Clinical Research nence, this project enhanced the intervention to include a connection with a local...

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Oral O2-01: Diagnosis and Clinical Course: Clinical Research

nence, this project enhanced the intervention to include a connection with a local Alzheimer’s Association office in order to improve primary care provided to older patients with cognitive impairment. Focus groups were conducted to understand barriers to referral and collaboration with community resources. Based on the findings, referral and information transmission forms were created and added to the practice design intervention, which also included: screening of older patients attending outpatient visits, physician education in the efficient approach to cognitive impairment, structured visit notes to guide care, patient education materials, and education about and materials to facilitate referral to the Alzheimer’s Association regional office. The effect of the intervention was measured using a pre/post methodology employing medical record audits. Qualitative interviews with physicians were also carried out. Results: Two large primary care practices on the west coast participated in the study. Physicians identified a variety of barriers to referral and collaboration with the Alzheimer’s Association offices including lack of familiarity, misunderstanding of the goals and capabilities of this resource, and lack of knowledge about how to refer patients. Approximately 10% of outpatients screened positive for cognitive impairment. Evaluation of the effect of the intervention is in progress. Conclusions: Primary care physicians caring for a large number older patients with cognitive impairment identified substantial barriers to referral of patients to regional Alzheimer’s Association offices. These were addressed in the dementia care practice-based intervention, including development of referral and information transfer materials. Findings from the intervention will be presented. S2-05-06


Richard Fortinsky, University of Connecticut Health Center, Farmington, CT, USA. Contact e-mail: [email protected] Background: Primary care physicians in the US have been shown to provide less than optimal care in terms of dementia diagnosis and management. Given the expected increase in patients with dementia visiting primary care, there is a clear need to link these physicians with other health and social care providers in the community. This presentation summarizes how primary care links presently developing in England may hold promise for the US, and explains an adapted primary care enhancement model under development in a defined geographic area informed by the English experience. Methods: Several months were spent in Yorkshire, England, where interviews were conducted with numerous health and social care providers to learn about how dementia care is organized under the National Health Service to enhance primary medical care for people with dementia and their family caregivers. These models were compared to several completed trials in the US carried out to enhance primary care for the same target population. An adapted care model was developed and presented to a community-based primary care physician network in a New England state for possible implementation. Results: Detailed aspects of the adapted model will be presented, as well as the status of its implementation. Conclusions: Ideas for improving the delivery of primary care for people with dementia care and their families can result from cross-national explorations of current care provider linkage strategies. MONDAY, JULY 28, 2008 ORAL O2-01 DIAGNOSIS AND CLINICAL COURSE: CLINICAL RESEARCH O2-01-01


Ronald C. Petersen, Rosebud Roberts, David S. Knopman, Yonas Geda, Vernon Pankratz, Bradley F. Boeve, Walter A. Rocca, Mayo Clinic, Rochester, MN, USA. Contact e-mail: [email protected]

Background: MCI has come to represent the prodromal stage of a variety of dementing disorders, but its frequency in a population-based setting is not known. Recent data have indicated a higher prevalence of MCI in men. Methods: Participants were randomly selected from among residents of Olmsted County, MN, on October 1, 2004. All subjects underwent a baseline evaluation including an interview of the subject and study partner by a nurse, a cognitive assessment, and a neurological exam by a physician. The evaluations were reviewed by a consensus panel including nurses, neuropsychologists, and physicians, and diagnoses of cognitively normal, MCI, and dementia were made according to published criteria. Participants were re-evaluated at 15-month intervals using the same protocol. Each subsequent evaluation was blinded to the previous clinical assessment. Results: Incidence rates were expressed as per 1,000 person-years of follow-up with 95% confidence intervals CI). Among 1,786 subjects eligible for re-evaluation with an 89.2% follow-up rate, the overall incidence of MCI was 52.9 (42.6, 64.9). The incidence was 35.3 (24.2, 49.9) in subjects 70-79 years at baseline and 71.9 (54.9, 92.6) for subjects 80-89 years. The incidence of MCI was greater for men 62.3 (46.8, 81.3) than for women 43.6 (30.8, 59.8) with a hazard ratio (HR) of 1.92 (95 % confidence interval (CI) ⫽ 1.22, 3.02). When examined by MCI subtype men had a higher HR of amnestic MCI (HR ⫽ 2.00, 95%CI ⫽ 1.12, 3.57) and non-amnestic MCI (HR ⫽ 1.82, 95% CI ⫽ 0.87, 3.81) compared to women after adjustment for age (as a continuous variable). Conclusions: The overall incidence of MCI in a population-based sample of subjects age 70 to 89 years was considerably higher than anticipated, increased with age, and was greater in men. The risk of MCI was consistently higher in men compared to women in both amnestic and non-amnestic MCI. The higher MCI incidence in men compared to women may partially explain the higher prevalence of MCI observed in men in this same population at baseline. O2-01-02


John C. S. Breitner, ADAPT Research Group, GRECC (S-182) VA Puget Sound HCS, Seattle, WA, USA. Contact e-mail: [email protected] Background: “Mild Cognitive Impairment” or MCI denotes cognitive disorder that does not qualify as dementia. A substantial subset of MCI includes prominent memory loss (amnestic MCI, or aMCI), and about half this group will progress to Alzheimer’s dementia (AD) over several years, at rates between 5% and 15% per year depending on diagnostic criteria. It is widely assumed, but not demonstrated, that most cases of incident AD emerge following a recognizable prodrome of aMCI or other cognitive impairment that is not dementia (CIND). Methods: Over an interval of 3.5 years the Alzheimer’s Disease Anti-inflammatory Prevention Trial (ADAPT) enrolled 2,528 individuals and followed them with sensitive annual cognitive examinations for 2 - 4 years (median 3.0 yrs). In this time, 75 people developed incident dementia, 64 with a research diagnosis of AD. We examined the percentage of incident AD cases who had been found to have CIND on at least one prior examination, further dividing this CIND group into those with aMCI or other clinical diagnosis of “prodromal AD” (prAD), and others. Results: Despite having undergone annual examinations beforehand, the 64 subjects with incident AD included more than a third who had received no prior diagnosis of any type of CIND. Furthermore, among those who had passed through a stage of CIND, slightly fewer than two-thirds could be identified as having had aMCI or prAD. It is known that the specificity of CIND as a predictor of AD is low (many “false positives” do not progress to dementia.) The table shows that the sensitivity of CIND as a predictor of AD is also low (only 66% of incident cases had been detected with any type of CIND, and only 45% with aMCI/prAD).

Oral O2-01: Diagnosis and Clinical Course: Clinical Research Individuals With Incident Dementia, Shown by Prior Cognitive Status Incident dementia type

Prior aMCI/prAD

All-cause dementia AD

31(41.3%) 29(45.3%)


Other CIND


16(21.3%) 13(20.3%)



28(37.3%) 22(34.4%)

*Numbers with (percent). 75 cases of incident dementia diagnosed by DSM-III-R criteria, 64 with AD diagnosed by NINCDS-ADRDA criteria.

Conclusions: These findings suggest that: 1) in the longitudinal study of large samples, aMCI and prAD are poor predictors of subsequent dementia; and 2) a surprising proportion of individuals with incident dementia appear to have developed their symptoms after a very brief or undetected stage of prior cognitive impairment. Provided sufficient numbers are available, the characteristics of the latter group deserve close inquiry. O2-01-03


Lia M. A. E. Baars, Martin P. J. van Boxtel, Pieter Jelle Visser, Frans R. J. Verhey, Jelle Jolles, Maastricht University, Maastricht, Netherlands. Contact e-mail: [email protected] Background: Transition from MCI to normal functioning is one main longitudinal outcome for MCI cases. This raises questions about the usability of the concept MCI as a clinical entity. It remains unclear to what extent effects of practice on neuropsychological test performance could explain the instability of MCI diagnosis over time, depending on the definition of MCI used. The aim of this study was to investigate the stability of MCI over time in a large population-based sample, by comparing different methods of measuring MCI stability. Methods: Data were taken from the Maastricht Aging Study, a large longitudinal study into the determinants of cognitive aging (Jolles, Houx et al. 1995). MCI was defined as impaired memory functioning (a score of at least 1.5 SD below the mean on at least one memory task), no dementia and normal ADL functioning. Three methods of stability were compared: M1 used the baseline MCI cut-off for the 3 and 6 years follow up (FU). For method M2, the MCI cut-off was calculated for each FU separately and in method M3, effects of practice for MCI cases were corrected for practice effects of healthy controls. Only participants of 60 years and older who completed three measurements were included in the current study (N⫽420). Results: 30 MCI cases were identified at baseline. For method M1 33.3% were still case at 3 years FU, and 56.7% were case after 6 years. With method M2, 40% were still case 3 years after baseline and 56.7% at 6 years FU. Method M3 showed a different pattern, with 13.3% stable MCI cases in the first 3 years and 56.7% after 6 years. Conclusions: MCI was found to be an instable condition over time, regardless of the definition used. In MAAS, MCI defined at baseline was the strongest predictor for dementia. The pattern of instability was indicative of regression-to-the-mean and should not be misinterpreted as being evidence for instability of prodromal cognitive disorders, but should be considered a consequence of using behavioural measures sensitive to learning effects to define them. These findings challenge the usefulness of the MCI concept in epidemiological studies. O2-01-04


Jose´ A. Luchsinger1, Adam M. Brickman1, Christiane Reitz1, Nicole Schupf1, Jennifer J. Manly1, Ming X. Tang1, Scott A. Small1, Richard Mayeux1, Charles DeCarli2, Truman R. Brown1, 1Columbia University, New York, NY, USA; 2UC-Davis, Davis, CA, USA. Contact e-mail: [email protected] Background: Cerebrovascular disease (CVD) is the main cause of vascular cognitive impairment and may be important in Alzheimer’s disease (AD). Mild cognitive impairment (MCI) is a transitional stage between normal cognition and dementia. Amnestic MCI (AMCI) is thought to be a transitional stage of Alzheimer’s disease (AD), while non-amnestic MCI (NAMCI) may be related to other causes including CVD. Objectives: We


sought to determine the cross-sectional relation of white matter hyperintensity volume (WMH) and infarcts in brain magnetic resonance imaging (MRI) with MCI. Methods: 679 elderly persons aged 80.0 ⫾ 5.6 years (67.6% women, 34.9% African American, 36.1% Hispanic, 29.0% White) without dementia and with MCI information underwent brain MRI. WMH and infarcts (ⱖ 3 mm) were quantified using standard research methods. WMH was adjusted for total cranial volume (TCV). WMH distribution was highly skewed and required logarithmic transformation. The definition of MCI was similar to the Petersen criteria. MCI was sub-classified into AMCI and NAMCI. We estimated odds ratios (OR) and 95% confidence intervals (CI) using logistic regression. Results: The prevalence of MCI was 25.2% (14.3% AMCI, 10.9% NAMCI). On average, 1.2 ⫾ 1.2 % of the TCV was occupied by WMH; 30.1% of the participants had infarcts on MRI. WMH was associated with AMCI (OR⫽1.9; 95% CI: 1,3.1) but not NAMCI (OR ⫽ 1.0; 95% CI: 0.6,1.8) after adjusting for demographics, APOE-⑀4, vascular risk factors, and infarcts. Presence of infarcts was strongly associated with NAMCI (OR ⫽2.6; 95% CI: 1.4,4.6) but not with AMCI (OR⫽1.2; 95% CI: 0.7,2.1) adjusting for demographics, APOE-⑀4, vascular risk factors, and WMH. Results were similar when quartiles of WMH were examined. Frontal lobe infarcts were significantly related to a higher risk of NAMCI. Conclusions: WMH was specifically related to AMCI, supporting previous studies relating WMH to AD. Infarcts were specifically related to NAMCI. The nature and mechanism of WMH in AMCI requires further study. O2-01-05


Henry Brodaty1, Perminder Sachdev2, Melissa Slavin2, Nicole Kochan2, Julian Trollor2, Brian Draper3, Tony Broe4, 1Dementia Collaborative Research Centre, University of New South Wales, Sydney, NSW, Australia; 2Brain Ageing Program, University of New South Wales, Randwick, NSW, Australia; 3Aged Care Psychiatry, Prince of Wales Hospital, Randwick, NSW, Australia; 4Medical Research Institute, University of New South Wales, Randwick, NSW, Australia. Contact email: [email protected] Background: We examined the construct of Subjective Cognitive Complaints (SCCs). Cognitive complaint, whether it relate to memory or another cognitive domain or emanate from individuals or informants is one criterion required for the diagnosis of Mild Cognitive Impairment (MCI). Yet SCC remains ill-defined. We posed several questions: What is the prevalence of SCCs as variously defined? What are the implications of complaints by a person versus by an informant? Spontaneous complaints versus responses to questions versus treatment seeking? Memory versus other cognitive complaints? How accurately do SCCs correspond to neuropsychological performance? How useful are SCCs for diagnosing MCI? Methods: Over 1000 community dwelling Sydney-siders, aged 70-90 years were recruited from the Australian Electoral Roll, where voting is compulsory. Comprehensive assessments included structured interviews, the MAC-Q, a battery of neuropsychological tests and informant interviews. Exclusion criteria included dementia, serious health problems and alcohol dependence. We present the results of the first 700 ratings of subjective and informant complaints regarding memory, language, visuospatial skills and executive functions and correlations with performance on corresponding tests. Cognitive impairment was defined as 1.5 standard deviations or more below normal for age and education. Results: 93% of participants and 74% of informants noted at least one cognitive complaint. Almost all participants (91%) corroborated informants’ complaints but only 61% of informants agreed with participants’ reports of SCCs. As regards objective performance, 58% of participants had no impairment, and 14% had memory single domain, 10% memory multiple domain, 15% non-memory single domain, and 3% non-memory multiple domain impairment. There were almost no significant correlations of memory or other cognitive complaints by subject or informant with relevant objective performance. Exceptions were memory and non-memory multiple domain impairment were both associated with seeing a doctor and visuo-spatial