Behavioral and psychological symptoms and hippocampal atrophy in subcortical ischaemic vascular disease

Tiel, Chan; Sudo, Felipe Kenji; Alves, Carlos Eduardo Oliveira; Alves, Gilberto Sousa; Ericeira-Valente, Letice; Moreira, Denise Madeira; Laks, Jerson; Engelhardt, Eliasz

doi:10.1590/S1980-57642012DN06030011

ABSTRACT

Background:

Neuropsychiatric symptoms are common in patients with cognitive impairments, mediated by both neurodegenerative processes and cerebrovascular disease. Previous studies have reported that Behavioral and Psychological Symptoms of Dementia (BPSD) might correlate with severity of cognitive decline. Thus far, the impact of the association between white-matter hyperintensities (WHM) and hippocampal atrophy (HA) on the incidence of these symptoms has been less studied.

Objective:

This cross-sectional study aimed to describe the clinical profile of a sample with large extensions of WMH, examining the association between different degrees of HA and cognitive, functional, and behavioral status.

Methods:

Fifty outpatients (mean age: 76.86±8.70 years; 58% female; mean schooling: 7.44±4.69 years) with large extensions of WMH (modified-Fazekas scale=3) on MRI and different degrees of hippocampal atrophy (according to de Leon Score) underwent cognitive, functional, and behavioral assessments.

Results:

Patients with mild-moderate to severe HA had worse performance on the Mini-Mental State Examination, Cambridge Cognitive Examination, Clinical Dementia Rating and Pfeffer's Functional Activities Questionnaire, compared to the group with none or questionable HA. Appetite/Eating Behavior was the only cluster of neuropsychiatric symptoms associated with presence of HA in Vascular Cognitive Impairment patients.

Discussion:

Although HA may exhibit distinct impact on cognitive performance and functional status, it appears to have little effect on behavioral symptoms in patients with high severity WMH.

Key words:
vascular dementia; executive function; neuropsychology; neuroimaging; cerebrovascular disease; neuropsychiatry

Resumo

Introdução:

Sintomas neuropsiquiátricos são comuns em pacientes com déficits cognitivos associados a processos neurodegenerativos e à doença cerebrovascular. Estudos apontaram que os Sintomas Comportamentais e Psicológicos da Demência (SCPD) podem ter relação com a gravidade do declínio cognitivo. Até o presente, o impacto da associação entre hiperintensidades da substância branca (HSB) e atrofia hipocampal (AH) sobre esses sintomas foi pouco explorado na literatura.

Objetivo:

Este estudo transversal objetiva descrever as características clínicas de uma amostra com extensas HSB, examinando a influência de diferentes graus de AH sobre os aspectos cognitivos, comportamentais e funcionais.

Métodos:

Cinquenta idosos atendidos em ambulatório (idade média: 76.86±8.70 anos; 58% mulheres; escolaridade média: 7.44±4.69 anos), com extensas HSB (escala modificada de Fazekas=3) e diferentes graus de AH (de acordo com a escala de de Leon) foram submetidos à avaliação cognitiva, funcional e comportamental.

Resultados:

Pacientes com AH leve-moderada a grave apresentaram piores pontuações no Mini-Exame do Estado Mental, Avaliação Cognitiva de Cambridge, Estadiamento Clínico da Demência e Questionário de Atividades Funcionais de Pfeffer, em comparação com indivíduos com AH ausente ou questionável. Apetite/Comportamento Alimentar foi o único grupo de sintomas neuropsiquiátricos associados à presença de AH em indivíduos com Comprometimento Cognitivo Vascular.

Discussão:

Embora a AH pareça apresentar impacto sobre desempenho cognitivo e funcional, parece apresentar pouca influência sobre sintomas comportamentais em pacientes com extensas HSB.

Palavras-chave:
demência vascular; função executiva; neuropsicologia; neuroimagem; doença cerebrovascular; neuropsiquiatria

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REFERENCES

Lyketsos CG, Steinberg M, Tschanz JT, et al. Mental and behavioral disturbances in dementia: findings from the cache county study on memory in aging. Am J Psychiatr 2000;157:708-714.
Aalten P, Verhey FR, Boziki M, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer disease consortium: part I. Dement Geriatr Cogn Disord 2007;24:457-463.
Caputo M, Monastero R, Mariani E, et al. Neuropsychiatric symptoms in 921 elderly subjects with dementia: a comparison between vascular and neurodegenerative types. Acta Psychiatr Scand 2008;117:455-464.
Hsieh CJ, Chang CC, Lin CC. Neuropsychiatric profiles of patients with Alzheimer's disease and vascular dementia in Taiwan. Int J Geriatr Psychiatr 2009;6:570-577.
Aharon-Peretz J, Daskovski E, Mashiach T, et al. Natural History of dementia associated with lacunar infarctions. J Neurol Sci 2002;203-204:53-55.
Staekenborg SS, Gillissen F, Romkes R, et al. Behavioural and psychological symptoms are not related to white matter hyperintensities and medial temporal lobe atrophy in Alzheimer's disease. Int J Geriatr Psychiatr y 2008;23:387-392.
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.
Rockwood K, Moorhouse PK, Song X, et al. Disease progression in vascular cognitive impairment: Cognitive, functional and behavioral outcomes in the consortium to investigate vascular impairment of cognition (CIVIC) cohort study. J Neurol Sci 2007;252:106-112.
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;236:43-48.
Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.
Hachinski VC, Iliff LD, Zilhka E, et al. Cerebral blood flow in dementia. Arch Neurol 1975;32:632-637.
Fazekas F, Chawluk JB, Alavi A, et al. MR signal abnormalities at 1.5T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol 1987;149:351-356.
Gouw AA, Van der Flier VW, Van Straaten ECW et al. Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study. J Neurol 2005; 253:1189-1196.
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.
Roth M, Tym E, Mountjoy CO, et al. CAMDEX: a standardized instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. Br J Psychiatry 1986;149: 698-709.
Hughes CP, Berg L, Danziger WL, et al. A new clinical scale for the staging of dementia. Br J Psychiatry 1982;140:566-572.
Chaves Ml, Camozzato Al, Godinho C, et al. Validity of the Clinical Dementia Rating scale for the detection and staging of dementia in Brazilian patients. Alzheimer Dis Assoc Disord 2007;21:210-217.
Pfeffer RI, Kurosaki TT, Harrah CH Jr, Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol 1982;37:323-329.
Camozzato Al, Kochhann R, Simeoni C, et al. Reliability of the Brazilian Portuguese version of the Neuropsychiatric Inventory (NPI) for patients with Alzheimer's disease and their caregivers. Int Psychogeriatr 2008;20:383-393.
de Leon M, George AE, Golomb J, et al. Frequency of hippocampal formation atrophy in normal aging and Alzheimer's disease. Neurobiol Aging. 1997;18:1-11.
de Leon M, Convit A, De Santi S, et al. Contribution of structural neuroimaging to the early diagnosis of Alzheimer's disease. Int Psychogeriatr 1997;9(Suppl1):183-190.
Tullberg M, Fletcher E, DeCarli C, et al. White matter lesions impair frontal lobe function regardless of their location. Neurology 2004;63:246-253.
Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA 2002;288:1475-1483.
Steinberg M, Sheppard JM, Tschanz JT, et al. The incidence of mental and behavioral disturbances in dementia: the cache county study. J Neuropsych Clin Neurosci 2003;15:340-345.
Chiu PY, Liu CH, Tsai CH. Neuropsychiatric manifestations in vascular cognitive impairment patients with and without dementia. Acta Neurol Taiwan 2007;16:86-91.
Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 2002;53:647-654.
Rosenberg PB, Mielke MM, Appleby B, et al. Neuropsychiatric symptoms in MCI subtypes: the importance of executive dysfunction. Int J Geriatr Psychiatr 2011;26:364-372.
Chiu MJ, Chen TF, Yip PK, Hua MS, Tang LY. Behavioral and psychologic symptoms in different types of dementia. J Formos Med Assoc 2006;105:556-562.
Klugman A, Marshall J, Tabet N. Impact of cerebrovascular pathology on behavioural and neuropsychiatric symptoms in patients with Alzheimer's dementia: findings from a retrospective, naturalistic study. Int J Clin Pract 2009;63:1024-1030.
Staekenborg SS, Su T, van Straaten ECW, et al. Behavioural and psychological symptoms in vascular dementia; differences between small- and large-vessel disease. J Neurol Neurosurg Psychiatry 2010;81:547-551.
O'Brien J. Behavioral Symptoms in Vascular Cognitive impairment and vascular dementia. Int Psychogeriatr 2003;15:133-138.
Cole J, Costafreda SG, McGuffin P, Fu CH. Hippocampal atrophy in first episode depression: a meta-analysis of magnetic resonance imaging studies. J Affect Disord 2011;134:283-487.
Margari F, Sicolo M, Spinelli L, et al. Aggressive behavior, cognitive impairment, and depressive symptoms in elderly subjects. Neuropsychiatr Dis Treat 2012;8:347-353.
Serra L, Perri R, Cercignani M, et al. Are the behavioral symptoms of Alzheimer's disease directly associated with neurodegeneration? J Alzheimers Dis 2010;21:627-639.
Ismail Z, Herrmann N, Rothenburg LS, et al. A functional neuroimaging study of appetite loss in Alzheimer's disease. J Neurol Sci 2008;271:97-103.
Berlow YA, Wells WM, Ellison JM, et al. Neuropsychiatric correlates of white matter hyperintensities in Alzheimer's disease. Int J Geriatr Psychiatr y 2010;25:780-788.

Publication Dates

Publication in this collection
Jul-Sep 2012

History

Received
08 June 2012
Accepted
22 Aug 2012

This is an open-access article distributed under the terms of the Creative Commons Attribution License

[1] Lyketsos CG, Steinberg M, Tschanz JT, et al. Mental and behavioral disturbances in dementia: findings from the cache county study on memory in aging. Am J Psychiatr 2000;157:708-714.

[2] Aalten P, Verhey FR, Boziki M, et al. Neuropsychiatric syndromes in dementia. Results from the European Alzheimer disease consortium: part I. Dement Geriatr Cogn Disord 2007;24:457-463.

[3] Caputo M, Monastero R, Mariani E, et al. Neuropsychiatric symptoms in 921 elderly subjects with dementia: a comparison between vascular and neurodegenerative types. Acta Psychiatr Scand 2008;117:455-464.

[4] Hsieh CJ, Chang CC, Lin CC. Neuropsychiatric profiles of patients with Alzheimer's disease and vascular dementia in Taiwan. Int J Geriatr Psychiatr 2009;6:570-577.

[5] Aharon-Peretz J, Daskovski E, Mashiach T, et al. Natural History of dementia associated with lacunar infarctions. J Neurol Sci 2002;203-204:53-55.

[6] Staekenborg SS, Gillissen F, Romkes R, et al. Behavioural and psychological symptoms are not related to white matter hyperintensities and medial temporal lobe atrophy in Alzheimer's disease. Int J Geriatr Psychiatr y 2008;23:387-392.

[7] Fuh JL, Wang SJ, Cummings JL. Neuropsychiatric profiles in patients with Alzheimer's disease and vascular dementia. J Neurol Neurosurg Psychiatry 2005;76:1337-1341.

[8] Rockwood K, Moorhouse PK, Song X, et al. Disease progression in vascular cognitive impairment: Cognitive, functional and behavioral outcomes in the consortium to investigate vascular impairment of cognition (CIVIC) cohort study. J Neurol Sci 2007;252:106-112.

[9] 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;236:43-48.

[10] Cummings JL, Mega M, Gray K, et al. The Neuropsychiatric Inventory: comprehensive assessment of psychopathology in dementia. Neurology 1994;44:2308-2314.

[11] Hachinski VC, Iliff LD, Zilhka E, et al. Cerebral blood flow in dementia. Arch Neurol 1975;32:632-637.

[12] Fazekas F, Chawluk JB, Alavi A, et al. MR signal abnormalities at 1.5T in Alzheimer's dementia and normal aging. AJR Am J Roentgenol 1987;149:351-356.

[13] Gouw AA, Van der Flier VW, Van Straaten ECW et al. Simple versus complex assessment of white matter hyperintensities in relation to physical performance and cognition: the LADIS study. J Neurol 2005; 253:1189-1196.

[14] 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.

[15] Roth M, Tym E, Mountjoy CO, et al. CAMDEX: a standardized instrument for the diagnosis of mental disorder in the elderly with special reference to the early detection of dementia. Br J Psychiatry 1986;149: 698-709.

[16] Hughes CP, Berg L, Danziger WL, et al. A new clinical scale for the staging of dementia. Br J Psychiatry 1982;140:566-572.

[17] Chaves Ml, Camozzato Al, Godinho C, et al. Validity of the Clinical Dementia Rating scale for the detection and staging of dementia in Brazilian patients. Alzheimer Dis Assoc Disord 2007;21:210-217.

[18] Pfeffer RI, Kurosaki TT, Harrah CH Jr, Chance JM, Filos S. Measurement of functional activities in older adults in the community. J Gerontol 1982;37:323-329.

[19] Camozzato Al, Kochhann R, Simeoni C, et al. Reliability of the Brazilian Portuguese version of the Neuropsychiatric Inventory (NPI) for patients with Alzheimer's disease and their caregivers. Int Psychogeriatr 2008;20:383-393.

[20] de Leon M, George AE, Golomb J, et al. Frequency of hippocampal formation atrophy in normal aging and Alzheimer's disease. Neurobiol Aging. 1997;18:1-11.

[21] de Leon M, Convit A, De Santi S, et al. Contribution of structural neuroimaging to the early diagnosis of Alzheimer's disease. Int Psychogeriatr 1997;9(Suppl1):183-190.

[22] Tullberg M, Fletcher E, DeCarli C, et al. White matter lesions impair frontal lobe function regardless of their location. Neurology 2004;63:246-253.

[23] Lyketsos CG, Lopez O, Jones B, et al. Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. JAMA 2002;288:1475-1483.

[24] Steinberg M, Sheppard JM, Tschanz JT, et al. The incidence of mental and behavioral disturbances in dementia: the cache county study. J Neuropsych Clin Neurosci 2003;15:340-345.

[25] Chiu PY, Liu CH, Tsai CH. Neuropsychiatric manifestations in vascular cognitive impairment patients with and without dementia. Acta Neurol Taiwan 2007;16:86-91.

[26] Tekin S, Cummings JL. Frontal-subcortical neuronal circuits and clinical neuropsychiatry: an update. J Psychosom Res 2002;53:647-654.

[27] Rosenberg PB, Mielke MM, Appleby B, et al. Neuropsychiatric symptoms in MCI subtypes: the importance of executive dysfunction. Int J Geriatr Psychiatr 2011;26:364-372.

[28] Chiu MJ, Chen TF, Yip PK, Hua MS, Tang LY. Behavioral and psychologic symptoms in different types of dementia. J Formos Med Assoc 2006;105:556-562.

[29] Klugman A, Marshall J, Tabet N. Impact of cerebrovascular pathology on behavioural and neuropsychiatric symptoms in patients with Alzheimer's dementia: findings from a retrospective, naturalistic study. Int J Clin Pract 2009;63:1024-1030.

[30] Staekenborg SS, Su T, van Straaten ECW, et al. Behavioural and psychological symptoms in vascular dementia; differences between small- and large-vessel disease. J Neurol Neurosurg Psychiatry 2010;81:547-551.

[31] O'Brien J. Behavioral Symptoms in Vascular Cognitive impairment and vascular dementia. Int Psychogeriatr 2003;15:133-138.

[32] Cole J, Costafreda SG, McGuffin P, Fu CH. Hippocampal atrophy in first episode depression: a meta-analysis of magnetic resonance imaging studies. J Affect Disord 2011;134:283-487.

[33] Margari F, Sicolo M, Spinelli L, et al. Aggressive behavior, cognitive impairment, and depressive symptoms in elderly subjects. Neuropsychiatr Dis Treat 2012;8:347-353.

[34] Serra L, Perri R, Cercignani M, et al. Are the behavioral symptoms of Alzheimer's disease directly associated with neurodegeneration? J Alzheimers Dis 2010;21:627-639.

[35] Ismail Z, Herrmann N, Rothenburg LS, et al. A functional neuroimaging study of appetite loss in Alzheimer's disease. J Neurol Sci 2008;271:97-103.

[36] Berlow YA, Wells WM, Ellison JM, et al. Neuropsychiatric correlates of white matter hyperintensities in Alzheimer's disease. Int J Geriatr Psychiatr y 2010;25:780-788.

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