Elsevier

Biological Psychiatry

Volume 57, Issue 4, 15 February 2005, Pages 412-421
Biological Psychiatry

Original articles
Regional cerebral metabolism in early Alzheimer’s disease with clinically significant apathy or depression

https://doi.org/10.1016/j.biopsych.2004.11.035Get rights and content

Background

Alzheimer’s disease (AD) is clinically characterized by cognitive impairment and behavioral disturbances. The aim of the study was to identify regional alterations in brain function associated with neuropsychiatric symptoms in early AD.

Methods

Patients underwent measures of cerebral glucose metabolism applying positron emission tomography (PET) and 18F-fluorodeoxyglucose. Neuropsychiatric symptoms were assessed using the Neuropsychiatric Inventory (NPI). Positron emission tomography images of patients suffering a neuropsychiatric symptom of clinical significance (NPI subscore for a specific item ≥4 points) were compared with the images of patients without the specific symptom under study (NPI subscore for a specific item = 0 points).

Results

A total of 53 patients with AD (Mini-Mental State Examination [MMSE] 22.5 ± 2.94 points) entered the study. Of all symptoms, apathy and depression were most frequently encountered. The patient group with apathy (n = 17) revealed significant decreases in left orbitofrontal regions when compared with patients free of apathy. Depression of clinical significance (n = 10) was associated with hypometabolism in dorsolateral prefrontal regions.

Conclusions

These findings support the notion that different functional circuits underlie apathy and depression in early AD.

Section snippets

Patients

A total of 155 patients older than 55 years and complaining of memory deficits were referred to the memory disorder clinics of two centers participating in a prospective multicenter European study (NEST-DD, Dresden and Cologne). Patients were eligible for study participation in NEST-DD if the Mini-Mental State Examination (MMSE) (Folstein et al 1975) revealed a minimum score of 20 points; the score obtained in the Clinical Dementia Rating Scale (CDR) (Morris 1993) did not exceed 2; and if

Results

Principle demographic and clinical data are given in Table 1. The rather high educational level of the patient group under study (12.2 years on average and a range from 8 to 18 years) may be attributed to the fact that both centers are university hospitals. The majority of subjects were newly diagnosed AD patients. Of the 53 patients, only 19 patients therefore received medication for dementia and only 1 patient received psychotropic medication. The time since onset of symptoms (duration of

Discussion

The aim of the study was to identify brain areas implicated in behavioral disturbances in early AD. Noncognitive symptoms have been shown to fluctuate (Hope et al 1999; Levy et al 1996a) and to steadily become more frequent throughout progression of the disease (Levy et al 1996a; Lopez et al 2003; Lyketsos et al 2001a; Mega et al 1996; Tractenberg et al 2000), but overall no comprehensive etiological and pathophysiological picture seems to emerge. It has been suggested that this lack of clarity

References (118)

  • O. Migneco et al.

    Perfusion brain SPECT and statistical parametric mapping analysis indicate that apathy is a cingulate syndromeA study in Alzheimer’s disease and nondemented patients

    Neuroimage

    (2001)
  • J.T. Olin et al.

    Provisional diagnostic criteria for depression of Alzheimer diseaseRationale and background

    Am J Geriatr Psychiatry

    (2002)
  • J.T. Olin et al.

    Provisional diagnostic criteria for depression of Alzheimer disease

    Am J Geriatr Psychiatry

    (2002)
  • L.S. Schneider et al.

    National Institute of Mental Health Clinical Antipsychotic Trials of Intervention Effectiveness (CATIE)Alzheimer disease trial methodology

    Am J Geriatr Psychiatry

    (2001)
  • F. Assal et al.

    Neuropsychiatric symptoms in the dementias

    Curr Opin Neurol

    (2002)
  • J.T. Becker et al.

    The natural history of Alzheimer’s disease. Description of study cohort and accuracy of diagnosis

    Arch Neurol

    (1994)
  • C.J. Bench et al.

    The anatomy of melancholia–focal abnormalities of cerebral blood flow in major depression

    Psychol Med

    (1992)
  • G. Binetti et al.

    Behavioral disorders in Alzheimer diseaseA transcultural perspective

    Arch Neurol

    (1998)
  • H. Braak et al.

    Neuropathological stageing of Alzheimer-related changes

    Acta Neuropathol (Berl)

    (1991)
  • E.B. Bromfield et al.

    Cerebral metabolism and depression in patients with complex partial seizures

    Arch Neurol

    (1992)
  • A. Burns et al.

    Psychiatric phenomena in Alzheimer’s disease: I: Disorders of thought content

    Br J Psychiatry

    (1990)
  • A. Burns et al.

    Psychiatric phenomena in Alzheimer’s disease: II: Disorders of perception

    Br J Psychiatry

    (1990)
  • A. Burns et al.

    Psychiatric phenomena in Alzheimer’s disease: III: Disorders of mood

    Br J Psychiatry

    (1990)
  • A. Burns et al.

    Psychiatric phenomena in Alzheimer’s disease: IV: Disorders of behaviour

    Br J Psychiatry

    (1990)
  • R. Cacabelos et al.

    Behavioral changes associated with different apolipoprotein E genotypes in dementia

    Alzheimer Dis Assoc Disord

    (1997)
  • C.S. Carter et al.

    The contribution of the anterior cingulate cortex to executive processes in cognition

    Rev Neurosci

    (1999)
  • M.P. Copeland et al.

    Psychiatric symptomatology and prodromal Alzheimer’s disease

    Alzheimer Dis Assoc Disord

    (2003)
  • E.H. Corder et al.

    Gene dose of apolipoprotein E type 4 allele and the risk of Alzheimer’s disease in late onset families

    Science

    (1993)
  • J.L. Cummings

    Theories behind existing scales for rating behavior in dementia

    Int Psychogeriatr

    (1996)
  • J.L. Cummings

    The Neuropsychiatric InventoryAssessing psychopathology in dementia patients

    Neurology

    (1997)
  • J.L. Cummings

    Progress in the management of behavioral symptoms in Alzheimer’s disease

    Alzheimer Insights

    (1999)
  • J.L. Cummings et al.

    The Neuropsychiatric InventoryComprehensive assessment of psychopathology in dementia

    Neurology

    (1994)
  • D.P. Devanand et al.

    Behavioral syndromes in Alzheimer’s disease

    Int Psychogeriatr

    (1992)
  • C. Donaldson et al.

    Determinants of carer stress in Alzheimer’s disease

    Int J Geriatr Psychiatry

    (1998)
  • J.R. Dura et al.

    Anxiety and depressive disorders in adult children caring for demented parents

    Psychol Aging

    (1991)
  • A. Eustace et al.

    A longitudinal evaluation of behavioural and psychological symptoms of probable Alzheimer’s disease

    Int J Geriatr Psychiatry

    (2002)
  • L.A. Farrer et al.

    Effects of age, sex, and ethnicity on the association between apolipoprotein E genotype and Alzheimer disease. A meta-analysis. APOE and Alzheimer Disease Meta Analysis Consortium

    JAMA

    (1997)
  • S.I. Finkel et al.

    Behavioral and psychological signs and symptoms of dementiaA consensus statement on current knowledge and implications for research and treatment

    Int Psychogeriatr

    (1996)
  • A.G. Fitz et al.

    Depression, cognition, and functional ability in patients with Alzheimer’s disease

    J Am Geriatr Soc

    (1994)
  • Y. Forsell et al.

    Major depression in a population of demented and nondemented older peoplePrevalence and correlates

    J Am Geriatr Soc

    (1998)
  • G.B. Frisoni et al.

    Behavioral syndromes in Alzheimer’s diseaseDescription and correlates

    Dement Geriatr Cogn Disord

    (1999)
  • K. Friston et al.

    Spatial registration and normalization of images

    Hum Brain Mapp

    (1995)
  • K. Friston et al.

    Statistical parametric maps in functional imagingA general linear approach

    Hum Brain Mapp

    (1995)
  • R. Fukuhara et al.

    Alteration of rCBF in Alzheimer’s disease patients with delusions of theft

    Neuroreport

    (2001)
  • T. Gabryelewicz et al.

    Behavioural pathology in Alzheimer’s disease with special reference to apolipoprotein E genotype

    Dement Geriatr Cogn Disord

    (2002)
  • D.W. Gilley et al.

    Psychotic symptoms and physically aggressive behavior in Alzheimer’s disease

    J Am Geriatr Soc

    (1997)
  • M.T. Gonzalez-Salvador et al.

    The stress and psychological morbidity of the Alzheimer patient caregiver

    Int J Geriatr Psychiatry

    (1999)
  • M. Hamilton

    A rating scale for depression

    J Neurol Neurosurg Psychiatry

    (1967)
  • D.G. Harwood et al.

    Relationship of behavioral and psychological symptoms to cognitive impairment and functional status in Alzheimer’s disease

    Int J Geriatr Psychiatry

    (2000)
  • N. Hirono et al.

    Frontal lobe hypometabolism and depression in Alzheimer’s disease

    Neurology

    (1998)
  • Cited by (0)

    View full text