Alzheimer Disease: Montine T

Tsuang D, Larson EB, Bolen E, Thompson ML, Peskind E, Bowen J, McCormick W, Teri L, Kukull W, Vavrek D, Montine T, Leverenz JB. · Veterans Affairs Northwest Network Mental Illness Research, Education, and Clinical Center, USA. · Am J Geriatr Psychiatry. · Pubmed #19307860 No free full text.

Abstract: OBJECTIVE: Several studies have demonstrated that specific neuropathologic features may be associated with the presence of visual hallucinations in dementia patients, but the clinical usefulness of these studies has been limited because their subjects were selected on the basis of neuropathologic findings rather than clinical presentations. This study seeks to investigate the demographic, clinical, and neuropathologic features of community-based dementia subjects with and without visual hallucations. DESIGN: A prospective examination of the clinical and neuropathologic correlates of visual hallucinations in community-based dementia subjects. PARTICIPANTS: One hundred forty-eight subjects with sufficient clinical and neuropathologic data from a community-based incident dementia autopsy case series. RESULTS: Subjects were classified according to the presence or absence of visual hallucinations and subjects with visual hallucinations (N = 27) were younger at intake and more likely to exhibit agitation, delusions, and apathy than subjects without visual hallucinations (N = 121). Subjects with visual hallucinations were also more likely than subjects without visual hallucinations to have Lewy-related pathology (LRP) (78% versus 45%). In addition, a higher frequency of visual hallucinations was observed in subjects with neocortical LRP than subjects with limbic-, amygdala-, or brainstem-predominant LRP. Although Alzheimer disease with concomitant LRP was the most common neuropathologic subtype in the visual hallucinations-positive group (59%), the frequency of subjects with Alzheimer disease pathology did not differ significantly between those with and without visual hallucinations (74% versus 62%). CONCLUSIONS: Subjects with visual hallucinations were more likely to have concomitant postural and gait disturbance, additional neuropsychiatric symptoms, and neocortical LRP than subjects without visual hallucinations. Visual hallucinations accompanying dementia have distinct clinical and neuropathologic characteristics that are important for prognosis and clinical management.

Erten-Lyons D, Woltjer RL, Dodge H, Nixon R, Vorobik R, Calvert JF, Leahy M, Montine T, Kaye J. · Veterans Affairs Medical Center, Portland, OR, USA. · Neurology. · Pubmed #19171833 No free full text.

Abstract: BACKGROUND: Autopsy series have shown that some elderly people remain with normal cognitive function during life despite having high burdens of pathologic lesions associated with Alzheimer disease (AD) at death. Understanding why these individuals show no cognitive decline, despite high AD pathologic burdens, may be key to discovery of neuroprotective mechanisms. METHODS: A total of 36 subjects who on autopsy had Braak stage V or VI and moderate or frequent neuritic plaque scores based on Consortium to Establish a Registry for Alzheimer's Disease (CERAD) standards were included. Twelve had normal cognitive function and 24 a diagnosis of AD before death. Demographic characteristics, clinical and pathologic data, as well as antemortem brain volumes were compared between the groups. RESULTS: In multiple regression analysis, antemortem hippocampal and total brain volumes were significantly larger in the group with normal cognitive function after adjusting for gender, age at MRI, time from MRI to death, Braak stage, CERAD neuritic plaque score, and overall presence of vascular disease. CONCLUSION: Larger brain and hippocampal volumes were associated with preserved cognitive function during life despite a high burden of Alzheimer disease (AD) pathologic lesions at death. A better understanding of processes that lead to preservation of brain volume may provide important clues for the discovery of mechanisms that protect the elderly from AD.

House MJ, St Pierre TG, Kowdley KV, Montine T, Connor J, Beard J, Berger J, Siddaiah N, Shankland E, Jin LW. · School of Physics, University of Western Australia, Perth, Australia. · Magn Reson Med. · Pubmed #17191232 No free full text.

Abstract: Iron accumulates in the Alzheimer's disease (AD) brain and is directly associated with beta-amyloid pathology. The proton transverse relaxation rate (R(2)) has a strong linear relationship with iron concentrations in healthy brain tissue; however, an independent test of this relationship has not been extended to AD brain tissue. In this study in vitro single spin-echo (SE) measurements were made on tissue samples from four human AD brains using a 4.7T MRI research scanner. R(2) values were calculated for 14 cortical and subcortical gray matter (GM) and white matter (WM) regions. Atomic absorption spectroscopy was used to measure iron concentrations in the corresponding excised brain regions. Significant positive linear correlations were observed between R(2) values and iron concentrations in GM regions assessed across individual tissue samples and data averaged by brain region. With the use of a predictive model for R(2), a threshold iron concentration of 55 microg Fe/g wet tissue was determined above which R(2) appears to be dominated by the affects of iron in AD brain tissue. High-field MRI may therefore be a useful research tool for assessing brain iron changes associated with AD.

Tsuang D, Simpson K, Larson EB, Peskind E, Kukull W, Bowen JB, McCormick W, Teri L, Montine T, Thompson ML, Leverenz JB. · University of Washington Departments of Psychiatry and Behavioral Sciences, Seattle, WA, USA. · J Geriatr Psychiatry Neurol. · Pubmed #17085757 No free full text.

Abstract: Accurate antemortem prediction of Lewy body pathology in patients with dementia is problematic. This study generates a model that better predicts Lewy body pathology in community-based patients with clinical Alzheimer's disease. Lewy body pathology was detected in 80 of 152 participants (52.6%) with an initial diagnosis of probable Alzheimer's disease. In a stepwise logistic regression model, female gender, lower education, being married, bradykinesia, hallucinations, and absence of irritability predicted the greatest likelihood of Lewy body pathology. The predictive model correctly diagnosed Lewy body pathology with an estimated sensitivity of 75%, specificity of 68%, and accuracy of 72%; the area under the receiver operating characteristic curve was 0.75. In a community-based autopsy sample, this predictive model confirmed parkinsonism and hallucinations as important predictors of Lewy body pathology in patients with clinical Alzheimer's disease. The model also identified other demographic and clinical characteristics that might enhance the prediction of Lewy body pathology.

Quinn J, Montine T, Morrow J, Woodward WR, Kulhanek D, Eckenstein F. · Portland Veteran's Affairs Medical Center, and Department of Neurology, Oregon Health Sciences University, 97201, USA. · J Neuroimmunol. · Pubmed #12667645 No free full text.

Abstract: The hypothesis that inflammation and beta amyloid deposition are causally linked in Alzheimer's disease (AD) was tested in a transgenic mouse model. Untreated beta amyloid plaque-bearing Tg2576 mice did not differ from wild type animals in brain levels of most inflammatory mediators. Indomethacin treatment suppressed brain levels of prostaglandins by 90%, but reduced hippocampal beta amyloid by only 20%, with no effect on cortical beta amyloid. The discordant effects on beta amyloid and cyclooxygenase (COX) suggest that these effects of nonsteroidal anti-inflammatory drugs (NSAIDs) are not causally linked. Further evidence against a causal relationship is seen in an unexpected trend to lower levels of beta amyloid after an inflammatory stimulus [lipopolysaccharide (LPS)].