Original Research Article
Association between Subcortical Lesions and Behavioral and Psychological Symptoms in Patients with Alzheimer's DiseasePalmqvist S.a · Sarwari A.a · Wattmo C.a · Bronge L.b · Zhang Y.c · Wahlund L.O.d · Nägga K.a
aClinical Memory Research Unit, Department of Clinical Sciences, Lund University, Malmö, and bCLINTEC, Division of Medical Imaging and Technology, cDepartment of Neuroradiology and dDepartment of Neurobiology, Care Sciences and Society, Section of Clinical Geriatrics, Karolinska Institutet, Karolinska University Hospital, Stockholm, Sweden
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Background/Aims: The most devastating features of Alz-heimer's disease (AD) are often the behavioral and psychological symptoms in dementia (BPSD). There is controversy as to whether subcortical lesions contribute to BPSD. The aim of this study was to examine the relationship between BPSD and subcortical lesions (white-matter lesions and lacunes) in AD. Methods: CT or MRI from 259 patients with mild-to-moderate AD were assessed with the Age-Related White Matter Changes scale. Linear measures of global and temporal atrophy and Mini-Mental State Examination scores were used to adjust for AD pathology and disease severity in logistic regression models with the BPSD items delusions, hallucinations, agitation, depression, anxiety, apathy and irritability. Results: Lacunes in the left basal ganglia were asso-ciated with delusions (OR 2.57, 95% CI 1.21-5.48) and hallucinations (OR 3.33, 95% CI 1.38-8.01) and lacunes in the right basal ganglia were associated with depression (OR 2.13, 95% CI 1.01-4.51). Conclusion: Lacunes in the basal ganglia resulted in a 2- to 3-fold increased risk of delusions, hallucinations and depression, when adjusting for cognition and atrophy. This suggests that basal ganglia lesions can contribute to BPSD in patients with AD, independently of the AD process.
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- Brookmeyer R, Johnson E, Ziegler-Graham K, Arrighi HM: Forecasting the global burden of Alzheimer's disease. Alzheimers Dement 2007;3:186-191.
- Cummings JL: Alzheimer's disease. N Engl J Med 2004;351:56-67.
- Scarmeas N, Brandt J, Albert M, Hadjigeorgiou G, Papadimitriou A, Dubois B, Sarazin M, Devanand D, Honig L, Marder K, Bell K, Wegesin D, Blacker D, Stern Y: Delusions and hallucinations are associated with worse outcome in Alzheimer disease. Arch Neurol 2005;62:1601-1608.
- Matsumoto N, Ikeda M, Fukuhara R, Shinagawa S, Ishikawa T, Mori T, Toyota Y, Matsumoto T, Adachi H, Hirono N, Tanabe H: Caregiver burden associated with behavioral and psychological symptoms of dementia in elderly people in the local community. Dement Geriatr Cogn Disord 2007;23:219-224.
- Hurt C, Bhattacharyya S, Burns A, Camus V, Liperoti R, Marriott A, Nobili F, Robert P, Tsolaki M, Vellas B, Verhey F, Byrne EJ: Patient and caregiver perspectives of quality of life in dementia. An investigation of the relationship to behavioural and psychological symptoms in dementia. Dement Geriatr Cogn Disord 2008;26:138-146.
- Berlow YA, Wells WM, Ellison JM, Sung YH, Renshaw PF, Harper DG: Neuropsychiatric correlates of white matter hyperintensities in Alzheimer's disease. Int J Geriatr Psychiatry 2010;25:780-788.
- Hirono N, Kitagaki H, Kazui H, Hashimoto M, Mori E: Impact of white matter changes on clinical manifestation of Alzheimer's disease: a quantitative study. Stroke 2000;31:2182-2188.
- Starkstein SE, Sabe L, Vazquez S, Di Lorenzo G, Martinez A, Petracca G, Teson A, Chemerinski E, Leiguarda R: Neuropsychological, psychiatric, and cerebral perfusion correlates of leukoaraiosis in Alzheimer's disease. J Neurol Neurosurg Psychiatry 1997;63:66-73.
- O'Brien J, Perry R, Barber R, Gholkar A, Thomas A: The association between white matter lesions on magnetic resonance imaging and noncognitive symptoms. Ann NY Acad Sci 2000;903:482-489.
- Harrell LE, Duvall E, Folks DG, Duke L, Bartolucci A, Conboy T, Callaway R, Kerns D: The relationship of high-intensity signals on magnetic resonance images to cognitive and psychiatric state in Alzheimer's disease. Arch Neurol 1991;48:1136-1140.
- Lind K, Jonsson M, Karlsson I, Sjogren M, Wallin A, Edman A: Depressive symptoms and white matter changes in patients with dementia. Int J Geriatr Psychiatry 2006;21:119-125.
- Lopez OL, Becker JT, Rezek D, Wess J, Boller F, Reynolds CF 3rd, Panisset M: Neuropsychiatric correlates of cerebral white-matter radiolucencies in probable Alzheimer's disease. Arch Neurol 1992;49:828-834.
- Staekenborg SS, Gillissen F, Romkes R, Pij-nenburg YA, Barkhof F, Scheltens P, van der Flier WM: Behavioural and psychological symptoms are not related to white matter hyperintensities and medial temporal lobe atrophy in Alzheimer's disease. Int J Geriatr Psychiatry 2008;23:387-392.
- Casanova MF, Starkstein SE, Jellinger KA: Clinicopathological correlates of behavioral and psychological symptoms of dementia. Acta Neuropathol 2011;122:117-135.
- Gouw AA, Seewann A, van der Flier WM, Barkhof F, Rozemuller AM, Scheltens P, Geurts JJ: Heterogeneity of small vessel disease: a systematic review of MRI and histopathology correlations. J Neurol Neurosurg Psychiatry 2011;82:126-135.
Bronge L: Magnetic resonance imaging in dementia. A study in brain white matter changes. Acta Radiol Suppl 2002;43:1-32.
- Jellinger KA: Prevalence and impact of cerebrovascular lesions in Alzheimer and Lewy body diseases. Neurodegener Dis 2010;7:112-115.
- Schmahmann JD, Smith EE, Eichler FS, Filley CM: Cerebral white matter: neuroanatomy, clinical neurology, and neurobehavioral correlates. Ann N Y Acad Sci 2008;1142:266-309.
- Schmidt R, Schmidt H, Haybaeck J, Loitfelder M, Weis S, Cavalieri M, Seiler S, En-zinger C, Ropele S, Erkinjuntti T, Pantoni L, Scheltens P, Fazekas F, Jellinger K: Heterogeneity in age-related white matter changes. Acta Neuropathol 2011;122:171-185.
- Snowdon DA, Greiner LH, Mortimer JA, Riley KP, Greiner PA, Markesbery WR: Brain infarction and the clinical expression of Alzheimer disease. The nun study. JAMA 1997;277:813-817.
- Inzitari D, Pracucci G, Poggesi A, Carlucci G, Barkhof F, Chabriat H, Erkinjuntti T, Fazekas F, Ferro JM, Hennerici M, Langhorne P, O'Brien J, Scheltens P, Visser MC, Wahlund LO, Waldemar G, Wallin A, Pantoni L: Changes in white matter as determinant of global functional decline in older independent outpatients: three year follow- up of LADIS (leukoaraiosis and disability) study cohort. BMJ 2009;339:b2477.
- Jokinen H, Gouw AA, Madureira S, Ylikoski R, van Straaten EC, van der Flier WM, Barkhof F, Scheltens P, Fazekas F, Schmidt R, Verdelho A, Ferro JM, Pantoni L, Inzitari D, Erkinjuntti T: Incident lacunes influence cognitive decline: the LADIS study. Neurology 2011;76:1872-1878.
- Bobinski M, Wegiel J, Wisniewski HM, Tarnawski M, Reisberg B, De Leon MJ, Miller DC: Neurofibrillary pathology-correlation with hippocampal formation atrophy in Alzheimer disease. Neurobiol Aging 1996;17:909-919.
- Archer HA, Edison P, Brooks DJ, Barnes J, Frost C, Yeatman T, Fox NC, Rossor MN: Amyloid load and cerebral atrophy in Alz-heimer's disease: an 11c-PIB positron emission tomography study. Ann Neurol 2006;60:145-147.
- Yavuz BB, Ariogul S, Cankurtaran M, Oguz KK, Halil M, Dagli N, Cankurtaran ES: hippocampal atrophy correlates with the severity of cognitive decline. Int Psychogeriatr 2007;19:767-777.
- Nielsen HM, Londos E, Minthon L, Janciauskiene SM: Soluble adhesion molecules and angiotensin-converting enzyme in dementia. Neurobiol Dis 2007;26:27-35.
- Folstein MF, Folstein SE, McHugh PR: ‘Mini-Mental State'. A practical method for grading the cognitive state of patients for the clinician. J Psychiatr Res 1975;12:189-198.
American Psychiatric Association: Diagnostic and statistical manual of mental disorders, ed 3, review. Arlington, American Psychiatric Association, 1987.
- McKhann G, Drachman D, Folstein M, Katzman R, Price D, Stadlan EM: Clinical diagnosis of Alzheimer's disease: report of the NINCDS-ADRDA work group under the auspices of Department of Health and Human Services task force on Alzheimer's disease. Neurology 1984;34:939-944.
- Palmqvist S, Hansson O, Minthon L, Londos E: Practical suggestions on how to differen-tiate dementia with Lewy bodies from Alz-heimer's disease with common cognitive tests. Int J Geriatr Psychiatry 2009;24:1405-1412.
McKhann GM, Knopman DS, Chertkow H, Hyman BT, Jack CR Jr, Kawas CH, Klunk WE, Koroshetz WJ, Manly JJ, Mayeux R, Mohs RC, Morris JC, Rossor MN, Scheltens P, Carillo MC, Thies B, Weintraub S, Phelps CH: The diagnosis of dementia due to Alz-heimer's disease: recommendations from the National Institute on Aging and the Alz-heimer's Association workgroup. Alzhei-mers Dement 2011;7:263-269.
- Cummings JL, Mega M, Gray K, Rosenberg-Thompson S, Carusi DA, Gornbein J: The neuropsychiatric inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.
- Zhang Y, Londos E, Minthon L, Wattmo C, Liu H, Aspelin P, Wahlund LO: Usefulness of computed tomography linear measurements in diagnosing Alzheimer's disease. Acta Radiol 2008;49:91-97.
- Wahlund L, Barkhof F, Fazekas F, Bronge L, Augustin M, Sjögren M, Wallin A, Ader H, Leys D, Pantoni L, Pasquier F, Erkinjuntti T, Scheltens P: A new rating scale for age-related white matter changes applicable to MRI and CT. Stroke 2001;32:1318-1322.
Altman DG: Practical Statistics for Medical Research, 1st ed. London, Chapman and Hall, 1991.
IBM SPSS: SPSS ver 19.0. Chicago, SPSS Inc., 2010.
- Piccininni M, Di Carlo A, Baldereschi M, Zaccara G, Inzitari D: Behavioral and psychological symptoms in Alzheimer's disease: frequency and relationship with duration and severity of the disease. Dement Geriatr Cogn Disord 2005;19:276-281.
- Fuh JL, Wang SJ, Cummings JL: Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia. J Neurol Neurosurg Psychiatry 2005;76:1337-1341.
- Cummings JL: Organic delusions: phenomenology, anatomical correlations, and review. Br J Psychiatry 1985;146:184-197.
- Cummings JL, Gosenfeld LF, Houlihan JP, McCaffrey T: Neuropsychiatric disturbances associated with idiopathic calcification of the basal ganglia. Biol Psychiatry 1983;18:591-601.
Danel T, Goudemand M, Ghawche F, Godefroy O, Pruvo JP, Vaiva G, Samaille E, Pandit F: Delusional melancholia and multiple lacunar infarcts of the basal ganglia (in French). Rev Neurol (Paris) 1991;147:60-62.
- McMurtray AM, Sultzer DL, Monserratt L, Yeo T, Mendez MF: Content-specific delusions from right caudate lacunar stroke: association with prefrontal hypometabolism. J Neuropsychiatry Clin Neurosci 2008;20:62-67.
- Perez-Costas E, Melendez-Ferro M, Roberts RC: Basal ganglia pathology in schizophrenia: dopamine connections and anomalies. J Neurochem 2010;113:287-302.
- Roselli F, Pisciotta NM, Perneczky R, Pennelli M, Aniello MS, De Caro MF, Ferrannini E, Tartaglione B, Defazio G, Rubini G, Livrea P: Severity of neuropsychiatric symptoms and dopamine transporter levels in dementia with Lewy bodies: A 123i-FP-CIT SPECT study. Mov Disord 2009;24:2097-2103.
- Caligiuri MP, Peavy G: An instrumental study of the relationship between extrapyramidal signs and psychosis in Alzheimer's disease. J Neuropsychiatry Clin Neurosci 2000;12:34-39.
- Gilley DW, Whalen ME, Wilson RS, Bennett DA: Hallucinations and associated factors in Alzheimer's disease. J Neuropsychiatry Clin Neurosci 1991;3:371-376.
- Lopez OL, Zivkovic S, Smith G, Becker JT, Meltzer CC, DeKosky ST: Psychiatric symptoms associated with cortical-subcortical dysfunction in Alzheimer's disease. J Neuropsychiatry Clin Neurosci 2001;13:56-60.
- Merello M, Sabe L, Teson A, Migliorelli R, Petracchi M, Leiguarda R, Starkstein S: Extrapyramidalism in Alzheimer's disease: prevalence, psychiatric, and neuropsychological correlates. J Neurol Neurosurg Psychiatry 1994;57:1503-1509.
- Simpson S, Allen H, Tomenson B, Burns A: Neurological correlates of depressive symptoms in Alzheimer's disease and vascular dementia. J Affect Disord 1999;53:129-136.
- Barber R, Scheltens P, Gholkar A, Ballard C, McKeith I, Ince P, Perry R, O'Brien J: White matter lesions on magnetic resonance imaging in dementia with Lewy bodies, Alzhei-mer's disease, vascular dementia, and normal aging. J Neurol Neurosurg Psychiatry 1999;67:66-72.
- Starkstein SE, Mizrahi R, Capizzano AA, Acion L, Brockman S, Power BD: Neuroimaging correlates of apathy and depression in Alzheimer's disease. J Neuropsychiatry Clin Neurosci 2009;21:259-265.
- Tagariello P, Girardi P, Amore M: Depression and apathy in dementia: same syndrome or different constructs? A critical review. Arch Gerontol Geriatr 2009;49:246-249.
- Verkaik R, Nuyen J, Schellevis F, Francke A: The relationship between severity of Alz-heimer's disease and prevalence of comorbid depressive symptoms and depression: a systematic review. Int J Geriatr Psychiatry 2007;22:1063-1086.
- Landes AM, Sperry SD, Strauss ME: Prevalence of apathy, dysphoria, and depression in relation to dementia severity in Alzheimer's disease. J Neuropsychiatry Clin Neurosci 2005;17:342-349.
Serra L, Perri R, Cercignani M, Spano B, Fadda L, Marra C, Carlesimo GA, Caltagirone C, Bozzali M: Are the behavioral symptoms of Alzheimer's disease directly associated with neurodegeneration? J Alzheimers Dis 2010;21:627-639.
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