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1.  Neuropsychiatric Symptoms and Executive Functioning in Patients with Mild Cognitive Impairment: Relationship to Caregiver Burden 
Background
Caregivers of patients with mild cognitive impairment (MCI) need similar levels of support services as Alzheimer’s disease (AD) caregivers, but it is unclear if this translates to increased caregiver burden.
Methods
135 participants and their caregivers (40 MCI, 55 AD and 40 normal controls, NC) completed questionnaires, and the patients were administered neuropsychological tests.
Results
The MCI caregivers reported significantly more overall caregiving burden than the NC, but less than the AD. They showed similar levels of emotional, physical and social burden as the AD caregivers. Among the MCI caregivers, the neuropsychiatric symptoms and executive functioning of the patients were related to a greater burden, and the caregivers with a greater burden reported lower life satisfaction and social support, and a greater need for support services.
Conclusion
These results indicate that MCI caregivers are at increased risk for caregiver stress, and they require enhanced assistance and/or education in caring for their loved ones.
doi:10.1159/000339955
PMCID: PMC3698846  PMID: 23128102
Mild cognitive impairment; Caregiver burden; Neuropsychology; Neuropsychiatric symptoms
2.  Temporoparietal hypometabolism is common in FTLD and is associated with imaging diagnostic errors 
Archives of neurology  2010;68(3):329-337.
Objective
To evaluate the cause of diagnostic errors in the visual interpretation of positron emission tomography scans with 18F-fluorodeoxyglucose (FDG-PET) in patients with frontotemporal lobar degeneration (FTLD) and Alzheimer's disease (AD).
Design
Twelve trained raters unaware of clinical and autopsy information independently reviewed FDG-PET scans and provided their diagnostic impression and confidence of either FTLD or AD. Six of these raters also recorded whether metabolism appeared normal or abnormal in 5 predefined brain regions in each hemisphere – frontal cortex, anterior cingulate cortex, anterior temporal cortex, temporoparietal cortex and posterior cingulate cortex. Results were compared to neuropathological diagnoses.
Setting
Academic medical centers
Patients
45 patients with pathologically confirmed FTLD (n=14) or AD (n=31)
Results
Raters had a high degree of diagnostic accuracy in the interpretation of FDG-PET scans; however, raters consistently found some scans more difficult to interpret than others. Unanimity of diagnosis among the raters was more frequent in patients with AD (27/31, 87%) than in patients with FTLD (7/14, 50%) (p = 0.02). Disagreements in interpretation of scans in patients with FTLD largely occurred when there was temporoparietal hypometabolism, which was present in 7 of the 14 FTLD scans and 6 of the 7 lacking unanimity. Hypometabolism of anterior cingulate and anterior temporal regions had higher specificities and positive likelihood ratios for FTLD than temporoparietal hypometabolism had for AD.
Conclusions
Temporoparietal hypometabolism in FTLD is common and may cause inaccurate interpretation of FDG-PET scans. An interpretation paradigm that focuses on the absence of hypometabolism in regions typically affected in AD before considering FTLD is likely to misclassify a significant portion of FTLD scans. Anterior cingulate and/or anterior temporal hypometabolism indicates a high likelihood of FTLD, even when temporoparietal hypometabolism is present. Ultimately, the accurate interpretation of FDG-PET scans in patients with dementia cannot rest on the presence or absence of a single region of hypometabolism, but must take into account the relative hypometabolism of all brain regions.
doi:10.1001/archneurol.2010.295
PMCID: PMC3058918  PMID: 21059987
3.  Validation of Consensus Panel Diagnosis in Dementia 
Archives of neurology  2010;67(12):1506-1512.
Background
The clinical diagnosis of dementing diseases largely depends upon the subjective interpretation of patient symptoms. Consensus panels are frequently used in research to determine diagnoses when definitive pathological findings are unavailable. Nevertheless, research on group decision-making indicates many factors can adversely influence panel performance.
Objective
To determine conditions that improve consensus panel diagnosis.
Design
Comparison of neuropathological diagnoses with individual and consensus panel diagnoses based on clinical summaries, FDG-PET scans, and summaries with scans.
Setting
Expert and trainee individual and consensus panel deliberations using a modified Delphi method in a pilot research study of the diagnostic utility of FDG-PET imaging.
Patients and Methods
Forty-five patients with pathologically confirmed Alzheimer’s disease or frontotemporal dementia. Statistical measures of diagnostic accuracy, agreement, and confidence for individual raters and panelists before and after consensus deliberations.
Results
The consensus protocol using trainees and experts surpassed the accuracy of individual expert diagnoses when clinical information elicited diverse judgments. In these situations, consensus was 3.5 times more likely to produce positive rather than negative changes in the accuracy and diagnostic certainty of individual panelists. A rule that forced group consensus was at least as accurate as majority and unanimity rules.
Conclusions
Using a modified Delphi protocol to arrive at a consensus diagnosis is a reasonable substitute for pathologic information. This protocol improves diagnostic accuracy and certainty when panelist judgments differ and is easily adapted to other research and clinical settings while avoiding potential pitfalls of group decision-making.
doi:10.1001/archneurol.2010.301
PMCID: PMC3178413  PMID: 21149812
4.  Caregiver support service needs for patients with mild cognitive impairment and Alzheimer’s disease 
Little is known about the service needs for persons caring for individuals with Mild Cognitive Impairment (MCI). In this study, the level of support service need for caregivers of individuals diagnosed with Alzheimer’s Disease (AD; N=55) and MCI (N=25) was compared to normal controls (NC; N=44). Study partners (i.e., caregivers) completed questionnaires about their service needs and participants’ neurobehavioral symptoms, functional abilities, and frailty. Total, social, and mental health service needs were significantly different among the three groups (p<.0001), with MCI and AD caregivers reporting more need for services as compared to the NC group. There was no significant difference between MCI and AD groups for total and social service need. In the MCI group, caregiver’s service need was related to neurobehavioral symptoms and frailty, whereas service need among the AD caregivers was related to functional disability and frailty. Caregivers of individuals with MCI are already experiencing a need for increased services comparable to that of individuals caring for AD patients, though the pattern of patient-related factors is different between the two patient groups. These findings suggest possible areas of intervention that could be considered at the earliest stages of memory loss.
doi:10.1097/WAD.0b013e3181aba90d
PMCID: PMC2877755  PMID: 19571729
mild cognitive impairment; Alzheimer’s disease; service need; support services; caregiver
5.  Predicting missing biomarker data in a longitudinal study of Alzheimer disease 
Lo, Raymond Y. | Jagust, William J. | Aisen, Paul | Jack, Clifford R. | Toga, Arthur W. | Beckett, Laurel | Gamst, Anthony | Soares, Holly | C. Green, Robert | Montine, Tom | Thomas, Ronald G. | Donohue, Michael | Walter, Sarah | Dale, Anders | Bernstein, Matthew | Felmlee, Joel | Fox, Nick | Thompson, Paul | Schuff, Norbert | Alexander, Gene | DeCarli, Charles | Bandy, Dan | Chen, Kewei | Morris, John | Lee, Virginia M.-Y. | Korecka, Magdalena | Crawford, Karen | Neu, Scott | Harvey, Danielle | Kornak, John | Saykin, Andrew J. | Foroud, Tatiana M. | Potkin, Steven | Shen, Li | Buckholtz, Neil | Kaye, Jeffrey | Dolen, Sara | Quinn, Joseph | Schneider, Lon | Pawluczyk, Sonia | Spann, Bryan M. | Brewer, James | Vanderswag, Helen | Heidebrink, Judith L. | Lord, Joanne L. | Petersen, Ronald | Johnson, Kris | Doody, Rachelle S. | Villanueva-Meyer, Javier | Chowdhury, Munir | Stern, Yaakov | Honig, Lawrence S. | Bell, Karen L. | Morris, John C. | Mintun, Mark A. | Schneider, Stacy | Marson, Daniel | Griffith, Randall | Clark, David | Grossman, Hillel | Tang, Cheuk | Marzloff, George | Toledo-Morrell, Leylade | Shah, Raj C. | Duara, Ranjan | Varon, Daniel | Roberts, Peggy | Albert, Marilyn S. | Pedroso, Julia | Toroney, Jaimie | Rusinek, Henry | de Leon, Mony J | De Santi, Susan M | Doraiswamy, P. Murali | Petrella, Jeffrey R. | Aiello, Marilyn | Clark, Christopher M. | Pham, Cassie | Nunez, Jessica | Smith, Charles D. | Given, Curtis A. | Hardy, Peter | Lopez, Oscar L. | Oakley, MaryAnn | Simpson, Donna M. | Ismail, M. Saleem | Brand, Connie | Richard, Jennifer | Mulnard, Ruth A. | Thai, Gaby | Mc-Adams-Ortiz, Catherine | Diaz-Arrastia, Ramon | Martin-Cook, Kristen | DeVous, Michael | Levey, Allan I. | Lah, James J. | Cellar, Janet S. | Burns, Jeffrey M. | Anderson, Heather S. | Laubinger, Mary M. | Bartzokis, George | Silverman, Daniel H.S. | Lu, Po H. | Graff-Radford MBBCH, Neill R | Parfitt, Francine | Johnson, Heather | Farlow, Martin | Herring, Scott | Hake, Ann M. | van Dyck, Christopher H. | MacAvoy, Martha G. | Benincasa, Amanda L. | Chertkow, Howard | Bergman, Howard | Hosein, Chris | Black, Sandra | Graham, Simon | Caldwell, Curtis | Hsiung, Ging-Yuek Robin | Feldman, Howard | Assaly, Michele | Kertesz, Andrew | Rogers, John | Trost, Dick | Bernick, Charles | Munic, Donna | Wu, Chuang-Kuo | Johnson, Nancy | Mesulam, Marsel | Sadowsky, Carl | Martinez, Walter | Villena, Teresa | Turner, Scott | Johnson, Kathleen B. | Behan, Kelly E. | Sperling, Reisa A. | Rentz, Dorene M. | Johnson, Keith A. | Rosen, Allyson | Tinklenberg, Jared | Ashford, Wes | Sabbagh, Marwan | Connor, Donald | Jacobson, Sandra | Killiany, Ronald | Norbash, Alexander | Nair, Anil | Obisesan, Thomas O. | Jayam-Trouth, Annapurni | Wang, Paul | Lerner, Alan | Hudson, Leon | Ogrocki, Paula | DeCarli, Charles | Fletcher, Evan | Carmichael, Owen | Kittur, Smita | Mirje, Seema | Borrie, Michael | Lee, T-Y | Bartha, Dr Rob | Johnson, Sterling | Asthana, Sanjay | Carlsson, Cynthia M. | Potkin, Steven G. | Preda, Adrian | Nguyen, Dana | Tariot, Pierre | Fleisher, Adam | Reeder, Stephanie | Bates, Vernice | Capote, Horacio | Rainka, Michelle | Hendin, Barry A. | Scharre, Douglas W. | Kataki, Maria | Zimmerman, Earl A. | Celmins, Dzintra | Brown, Alice D. | Gandy, Sam | Marenberg, Marjorie E. | Rovner, Barry W. | Pearlson, Godfrey | Anderson, Karen | Saykin, Andrew J. | Santulli, Robert B. | Englert, Jessica | Williamson, Jeff D. | Sink, Kaycee M. | Watkins, Franklin | Ott, Brian R. | Wu, Chuang-Kuo | Cohen, Ronald | Salloway, Stephen | Malloy, Paul | Correia, Stephen | Rosen, Howard J. | Miller, Bruce L. | Mintzer, Jacobo
Neurology  2012;78(18):1376-1382.
Objective:
To investigate predictors of missing data in a longitudinal study of Alzheimer disease (AD).
Methods:
The Alzheimer's Disease Neuroimaging Initiative (ADNI) is a clinic-based, multicenter, longitudinal study with blood, CSF, PET, and MRI scans repeatedly measured in 229 participants with normal cognition (NC), 397 with mild cognitive impairment (MCI), and 193 with mild AD during 2005–2007. We used univariate and multivariable logistic regression models to examine the associations between baseline demographic/clinical features and loss of biomarker follow-ups in ADNI.
Results:
CSF studies tended to recruit and retain patients with MCI with more AD-like features, including lower levels of baseline CSF Aβ42. Depression was the major predictor for MCI dropouts, while family history of AD kept more patients with AD enrolled in PET and MRI studies. Poor cognitive performance was associated with loss of follow-up in most biomarker studies, even among NC participants. The presence of vascular risk factors seemed more critical than cognitive function for predicting dropouts in AD.
Conclusion:
The missing data are not missing completely at random in ADNI and likely conditional on certain features in addition to cognitive function. Missing data predictors vary across biomarkers and even MCI and AD groups do not share the same missing data pattern. Understanding the missing data structure may help in the design of future longitudinal studies and clinical trials in AD.
doi:10.1212/WNL.0b013e318253d5b3
PMCID: PMC3345787  PMID: 22491869

Results 1-5 (5)