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BMC Neurology
Published in: BMC Neurology 1/2017

Open Access 01-12-2017 | Research article

Comparison of neuropsychiatric symptoms and diffusion tensor imaging correlates among patients with subcortical ischemic vascular disease and Alzheimer’s disease

Authors: Min-Chien Tu, Wen-Hui Huang, Yen-Hsuan Hsu, Chung-Ping Lo, Jie Fu Deng, Ching-Feng Huang

Published in: BMC Neurology | Issue 1/2017

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Abstract

Background

The causes of behavioral and psychological symptoms of dementia (BPSD) vary according to the dementia subtype and associated neuropathology. The present study aimed to (i) compare BPSD between patients with subcortical ischemic vascular disease (SIVD) and Alzheimer’s disease (AD) across stages, and (ii) explore the associations with diffusion tensor imaging (DTI) in the corpus callosum (CC) and other major fibers.

Methods

Twenty-four patients with SIVD and 32 with AD were recruited. Four domains of the Neuropsychiatric Inventory (NPI) (hyperactivity, psychosis, affective, and apathy) and two DTI parameters [fractional anisotropy (FA) and mean diffusivity (MD)] within the genu, body (BCC), and splenium (SCC) of the CC and other major fibers were assessed.

Results

Overall, the patients with clinical dementia rating (CDR) 1 ~ 2 had higher scores in apathy domain than those with CDR0.5. Among those with CDR1 ~ 2, SIVD had higher scores in apathy domain than AD. MD values in the BCC/SCC were positively correlated with total NPI score and psychosis, hyperactivity, and apathy domains. FA values in the SCC were inversely correlated with total NPI score and psychosis domain. The correlations were modified by age, the CASI, and CDR scores. Stepwise linear regression models suggested that FA value within the left superior longitudinal fasciculus predicted the hyperactivity domain. MD value within the SCC/left uncinate fasciculus and FA value within the GCC/left forceps major predicted the psychosis domain. MD value within the right superior longitudinal fasciculus and CDR predicted the apathy domain. Further analysis suggested distinct patterns of regression models between SIVD and AD patients.

Conclusion

White matter integrity within the BCC/SCC had associations with multi-domains of BPSD. Our study also identified important roles of regions other than the CC to individual domain of BPSD, including the left superior longitudinal fasciculus to the hyperactivity domain, the left uncinate fasciculus/forceps major to the psychosis domain, and the right superior longitudinal fasciculus to the apathy domain. The neuronal substrates in predicting BPSD were different between SIVD and AD patients. Of note, apathy, which was more profound in SIVD, was associated with corresponding fiber disconnection in line with dementia severity and global cognition decline.
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Literature
1.
Finkel SI, Burns A. BPSD consensus statement. Int Psychogeriatric Asso. 1999.
2.
Gilley DW, Bienias JL, Wilson RS, Bennett DA, Beck TL, Evans DA. Influence of behavioral symptoms on rates of institutionalization for persons with Alzheimer's disease. Psychol Med. 2004;34:1129–35.CrossRefPubMed
3.
Coen RF, Swanwick GR, O'Boyle CA, Coakley D. Behaviour disturbance and other predictors of carer burden in Alzheimer's disease. Int J Geriatr Psychiatry. 1997;12:331–6.CrossRefPubMed
4.
Lyketsos CG, Steinberg M, Tschanz JT, Norton MC, Steffens DC, Breitner JC. Mental and behavioral disturbances in dementia: findings from the Cache County study on memory in aging. Am J Psychiatry. 2000;157:708–14.CrossRefPubMed
5.
Fuh JL. Study of behavioral and psychological symptoms of dementia in Taiwan. Acta Neurol Taiwanica. 2006;15:154–60.
6.
Srikanth S, Nagaraja AV, Ratnavalli E. Neuropsychiatric symptoms in dementia-frequency, relationship to dementia severity and comparison in Alzheimer's disease, vascular dementia and frontotemporal dementia. J Neurol Sci. 2005;236:43–8.CrossRefPubMed
7.
Fuh JL, Wang SJ, Cummings JL. Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia. J Neurol Neurosurg Psychiatry. 2005;76:1337–41.CrossRefPubMedPubMedCentral
8.
D'Onofrio G, Sancarlo D, Panza F, Copetti M, Cascavilla L, Paris F, Seripa D, Matera MG, Solfrizzi V, Pellegrini F, Pilotto A. Neuropsychiatric symptoms and functional status in Alzheimer's disease and vascular dementia patients. Curr Alzheimer Res. 2012;9:759–71.CrossRefPubMed
9.
Hsieh CJ, Chang CC, Lin CC. Neuropsychiatric profiles of patients with Alzheimer's disease and vascular dementia in Taiwan. Int J Geriatr Psychiatry. 2009;24:570–7.CrossRefPubMed
10.
Erkinjuntti T, Inzitari D, Pantoni L, Wallin A, Scheltens P, Rockwood K, Roman GC, Chui H, Desmond DW. Research criteria for subcortical vascular dementia in clinical trials. J Neural Transm Suppl. 2000;59:23–30.PubMed
11.
Fernandez-Martinez M, Castro J, Molano A, Zarranz JJ, Rodrigo RM, Ortega R. Prevalence of neuropsychiatric symptoms in Alzheimer's disease and vascular dementia. Curr Alzheimer Res. 2008;5:61–9.CrossRefPubMed
12.
Mortimer JA, Ebbitt B, Jun SP, Finch MD. Predictors of cognitive and functional progression in patients with probable Alzheimer's disease. Neurology. 1992;42:1689–96.CrossRefPubMed
13.
Cohen-Mansfield J. Nonpharmacologic interventions for inappropriate behaviors in dementia: a review, summary, and critique. Am J Geriatr Psychiatry. 2001;9:361–81.CrossRefPubMed
14.
Lu PH, Lee GJ, Shapira J, Jimenez E, Mather MJ, Thompson PM, Bartzokis G, Mendez MF. Regional differences in white matter breakdown between frontotemporal dementia and early-onset Alzheimer's disease. J Alzheimers Dis. 2014;39:261–9.PubMedPubMedCentral
15.
Wang XD, Ren M, Zhu MW, Gao WP, Zhang J, Shen H, Lin ZG, Feng HL, Zhao CJ, Gao K. Corpus Callosum atrophy associated with the degree of cognitive decline in patients with Alzheimer's dementia or mild cognitive impairment: a meta-analysis of the region of interest structural imaging studies. J Psychiatr Res. 2015;63:10–9.CrossRefPubMed
16.
Frederiksen KS. Corpus Callosum in aging and dementia. Dan Med J. 2013;60:B4721.PubMed
17.
Hahn C, Lim HK, Won WY, Ahn KJ, Jung WS, Lee CU. Apathy and white matter integrity in Alzheimer's disease: a whole brain analysis with tract-based spatial statistics. PLoS One. 2013;8:e53493.CrossRefPubMedPubMedCentral
18.
Di Paola M, Spalletta G, Caltagirone C. In vivo structural neuroanatomy of corpus callosum in Alzheimer's disease and mild cognitive impairment using different MRI techniques: a review. J Alzheimers Dis. 2010;20:67–95.CrossRefPubMed
19.
Hofer S, Frahm J. Topography of the human corpus callosum revisited--comprehensive fiber tractography using diffusion tensor magnetic resonance imaging. NeuroImage. 2006;32:989–94.CrossRefPubMed
20.
Tighe SK, Oishi K, Mori S, Smith GS, Albert M, Lyketsos CG, Mielke MM. Diffusion tensor imaging of neuropsychiatric symptoms in mild cognitive impairment and Alzheimer's dementia. J Neuropsychiatry Clin Neurosci. 2012;24:484–8.CrossRefPubMedPubMedCentral
21.
Kim JW, Lee DY, Choo IH, Seo EH, Kim SG, Park SY, Woo JI. Microstructural alteration of the anterior cingulum is associated with apathy in Alzheimer disease. Am J Geriatr Psychiatry. 2011;19:644–53.CrossRefPubMed
22.
Ota M, Sato N, Nakata Y, Arima K, Uno M. Relationship between apathy and diffusion tensor imaging metrics of the brain in Alzheimer's disease. Int J Geriatr Psychiatry. 2012;27:722–6.CrossRefPubMed
23.
Wu MK, Lu YT. Huang CW, Lin PH, Chen NC, Lui CC, Chang WN, lee CC, Chang YT, Chen SF, Chang CC: clinical significance of cerebrovascular biomarkers and white matter tract integrity in Alzheimer disease: clinical correlations with neurobehavioral data in cross-sectional and after 18 months follow-ups. Medicine (Baltimore). 2015;94:e1192.CrossRefPubMedCentral
24.
Shyu YI, Yip PK. Factor structure and explanatory variables of the mini-mental state examination (MMSE) for elderly persons in Taiwan. J Formos Med Assoc. 2001;100:676–83.PubMed
25.
Hachinski VC, Iliff LD, Zilhka E, Du Boulay GH, McAllister VL, Marshall J, Russell RW, Symon L. Cerebral blood flow in dementia. Arch Neurol. 1975;32:632–7.CrossRefPubMed
26.
Albert MS, DeKosky ST, Dickson D, Dubois B, Feldman HH, Fox NC, Gamst A, Holtzman DM, Jagust WJ, Petersen RC, Snyder PJ, Carrillo MC, Thies B, Phelps CH. The diagnosis of mild cognitive impairment due to Alzheimer's disease: recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease. Alzheimers Dement. 2011;7:270–9.CrossRefPubMedPubMedCentral
27.
Chobanian AV, Bakris GL, Black HR, Cushman WC, Green LA, Izzo JL Jr, Jones DW, Materson BJ, Oparil S, Wright JT Jr, Roccella EJ. The seventh report of the joint National Committee on prevention, detection, evaluation, and treatment of high blood pressure: the JNC 7 report. JAMA. 2003;289:2560–72.CrossRefPubMed
28.
American Diabetes Association. Standards of medical care in diabetes - 2015. Diabetes Care. 2015;38:S1–S93.
29.
Levey AS, Bosch JP, Lewis JB, Greene T, Rogers N, Roth D. A more accurate method to estimate glomerular filtration rate from serum creatinine: a new prediction equation. Modification of diet in renal disease study group. Ann Intern Med. 1999;130:461–70.CrossRefPubMed
30.
Snyder S, Pendergraph B. Detection and evaluation of chronic kidney disease. Am Fam Physician. 2005;72:1723–32.PubMed
31.
Cannon CP, Brindis RG, Chaitman BR, Cohen DJ, Cross JT Jr, Drozda JP Jr, Fesmire FM, Fintel DJ, Fonarow GC, Fox KA, Gray DT, Harrington RA, Hicks KA, Hollander JE, Krumholz H, Labarthe DR, Long JB, Mascette AM, Meyer C, Peterson ED, Radford MJ, Roe MT, Richmann JB, Selker HP, Shahian DM, Shaw RE, Sprenger S, Swor R, Underberg JA, Van de Werf F, Weiner BH, Weintraub WS. 2013 ACCF/AHA key data elements and definitions for measuring the clinical management and outcomes of patients with acute coronary syndromes and coronary artery disease: a report of the American College of Cardiology Foundation/American Heart Association task force on clinical data standards (writing committee to develop acute coronary syndromes and coronary artery disease clinical data standards). Circulation. 2013;127:1052–89.CrossRefPubMed
32.
Morris JC. The clinical dementia rating (CDR): current version and scoring rules. Neurology. 1993;43:2412–4.CrossRefPubMed
33.
Lin KN, Wang PN, Liu HC, Teng EL. Cognitive abilities screening instrument, Chinese version 2.0 (CASI C-2.0): administration and clinical application. Acta Neurol Taiwanica. 2012;21:180–9.
34.
Aalten P, Verhey FR, Boziki M, Bullock R, Byrne EJ, Camus V, Caputo M, Collins D, De Deyn PP, Elina K, Frisoni G, Girtler N, Holmes C, Hurt C, Marriott A, Mecocci P, Nobili F, Ousset PJ, Reynish E, Salmon E, Tsolaki M, Vellas B, Robert PH. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer disease consortium: part I. Dement Geriatr Cogn Disord. 2007;24:457–63.CrossRefPubMed
35.
Fazekas F, Chawluk JB, Alavi A, Hurtig HI, Zimmerman RA. MR signal abnormalities at 1.5 T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol. 1987;149:351–6.CrossRefPubMed
36.
Sultzer DL, Levin HS, Mahler ME, High WM, Cummings JL. A comparison of psychiatric symptoms in vascular dementia and Alzheimer's disease. Am J Psychiatry. 1993;150:1806–12.CrossRefPubMed
37.
Kim JM, Lyons D, Shin IS, Yoon JS. Differences in the behavioral and psychological symptoms between Alzheimer's disease and vascular dementia: are the different pharmacologic treatment strategies justifiable. Hum Psychopharmacol. 2003;18:215–20.CrossRefPubMed
38.
39.
Boyle PA, Malloy PF. Treating apathy in Alzheimer's disease. Dement Geriatr Cogn Disord. 2004;17:91–9.CrossRefPubMed
40.
41.
Lavretsky H, Zheng L, Weiner MW, Mungas D, Reed B, Kramer JH, Jagust W, Chui H, Mack WJ. The MRI brain correlates of depressed mood, anhedonia, apathy, and anergia in older adults with and without cognitive impairment or dementia. Int J Geriatr Psychiatry. 2008;23:1040–50.CrossRefPubMedPubMedCentral
42.
Starkstein SE, Fedoroff JP, Price TR, Leiguarda R, Robinson RG. Apathy following cerebrovascular lesions. Stroke. 1993;24:1625–30.CrossRefPubMed
43.
Mega MS, Cummings JL, Fiorello T, Gornbein J. The spectrum of behavioral changes in Alzheimer's disease. Neurology. 1996;46:130–5.CrossRefPubMed
44.
Hollocks MJ, Lawrence AJ, Brookes RL, Barrick TR, Morris RG, Husain M, Markus HS. Differential relationships between apathy and depression with white matter microstructural changes and functional outcomes. Brain. 2015;138:3803–15.CrossRefPubMedPubMedCentral
45.
Aharon-Peretz J, Kliot D, Tomer R. Behavioral differences between white matter lacunar dementia and Alzheimer's disease: a comparison on the neuropsychiatric inventory. Dement Geriatr Cogn Disord. 2000;11:294–8.CrossRefPubMed
46.
Beaulieu C. The basis of anisotropic water diffusion in the nervous system - a technical review. NMR Biomed. 2002;15:435–55.CrossRefPubMed
47.
Xie R, Fang M, Zhou L, Fan S, Liu J, Quan H, Luo M, Qiu D. Diffusion tensor imaging detects Wallerian degeneration of the corticospinal tract early after cerebral infarction. Neural Regen Res. 2012;7:900–5.PubMedPubMedCentral
48.
Alves GS, Oertel Knochel V, Knochel C, Carvalho AF, Pantel J, Engelhardt E, Laks J. Integrating retrogenesis theory to Alzheimer's disease pathology: insight from DTI-TBSS investigation of the white matter microstructural integrity. Biomed Res Int. 2015;2015:291658.PubMedPubMedCentral
49.
Uchino A, Sawada A, Takase Y, Egashira R, Kudo S. Transient detection of early wallerian degeneration on diffusion-weighted MRI after an acute cerebrovascular accident. Neuroradiology. 2004;46:183–8.CrossRefPubMed
50.
Di Paola M, Di Iulio F, Cherubini A, Blundo C, Casini AR, Sancesario G, Passafiume D, Caltagirone C, Spalletta G. When, where, and how the corpus callosum changes in MCI and AD: a multimodal MRI study. Neurology. 2010;74:1136–42.CrossRefPubMed
51.
Kamali A, Flanders AE, Brody J, Hunter JV, Hasan KM. Tracing superior longitudinal fasciculus connectivity in the human brain using high resolution diffusion tensor tractography. Brain Struct Funct. 2014;219:269–81.CrossRefPubMed
52.
Fernández-Matarrubia M, Matías-Guiu JA, Cabrera-Martín MN, Moreno-Ramos T, Valles-Salgado M, Carreras JL, Matías-Guiu J. Different apathy clinical profile and neural correlates in behavioral variant frontotemporaldementia and Alzheimer's disease. Int J Geriatr Psychiatry. 2017. doi:10.​1002/​gps.​4695. [Epub ahead of print]
53.
Aguera-Ortiz L, Hernandez-Tamames JA, Martinez-Martin P, Cruz-Orduna I, Pajares G, Lopez-Alvarez J, Osorio RS, Sanz M, Olazaran J. Structural correlates of apathy in Alzheimer's disease: a multimodal MRI study. Int J Geriatr Psychiatry. 2016;
54.
Doherty MJ, Jayadev S, Watson NF, Konchada RS, Hallam DK. Clinical implications of splenium magnetic resonance imaging signal changes. Arch Neurol. 2005;62:433–7.CrossRefPubMed
55.
Keller A, Jeffries NO, Blumenthal J, Clasen LS, Liu H, Giedd JN, Rapoport JL. Corpus Callosum development in childhood-onset schizophrenia. Schizophr Res. 2003;62:105–14.CrossRefPubMed
56.
Sarrazin S, Poupon C, Linke J, Wessa M, Phillips M, Delavest M, Versace A, Almeida J, Guevara P, Duclap D, Duchesnay E, Mangin JF, Le Dudal K, Daban C, Hamdani N, D'Albis MA, Leboyer M, Houenou J. A multicenter tractography study of deep white matter tracts in bipolar I disorder: psychotic features and interhemispheric disconnectivity. JAMA Psychiatry. 2014;71:388–96.CrossRefPubMed
57.
Norman J. Two visual systems and two theories of perception: an attempt to reconcile the constructivist and ecological approaches. Behav Brain Sci. 2002;25:73–96. discussion 96-144PubMed
58.
Hatton SN, Lagopoulos J, Hermens DF, Hickie IB, Scott E, Bennett MR. White matter tractography in early psychosis: clinical and neurocognitive associations. J Psychiatry Neurosci. 2014;39:417–27.CrossRefPubMedPubMedCentral
59.
Zeng B, Ardekani BA, Tang Y, Zhang T, Zhao S, Cui H, Fan X, Zhuo K, Li C, Xu Y, Goff DC, Wang J. Abnormal white matter microstructure in drug-naive first episode schizophrenia patients before and after eight weeks of antipsychotic treatment. Schizophr Res. 2016;172:1–8.CrossRefPubMed
60.
Banno K, Nakaaki S, Sato J, Torii K, Narumoto J, Miyata J, Hirono N, Furukawa TA, Mimura M, Akechi T. Neural basis of three dimensions of agitated behaviors in patients with Alzheimer disease. Neuropsychiatr Dis Treat. 2014;10:339–48.PubMedPubMedCentral
61.
Balthazar ML, Pereira FR, Lopes TM, da Silva EL, Coan AC, Campos BM, Duncan NW, Stella F, Northoff G, Damasceno BP, Cendes F. Neuropsychiatric symptoms in Alzheimer's disease are related to functional connectivity alterations in the salience network. Hum Brain Mapp. 2014;35:1237–46.CrossRefPubMed
Metadata
Title
Comparison of neuropsychiatric symptoms and diffusion tensor imaging correlates among patients with subcortical ischemic vascular disease and Alzheimer’s disease
Authors
Min-Chien Tu
Wen-Hui Huang
Yen-Hsuan Hsu
Chung-Ping Lo
Jie Fu Deng
Ching-Feng Huang
Publication date
01-12-2017
Publisher
BioMed Central
Published in
BMC Neurology / Issue 1/2017
Electronic ISSN: 1471-2377
DOI
https://doi.org/10.1186/s12883-017-0911-5

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