Neuropsychiatric symptoms in Alzheimer's disease: Past progress and anticipation of the future

Neuropsychiatric symptoms (NPS) in Alzheimer's disease (AD) are widespread and disabling. This has been known since Dr. Alois Alzheimer's first case, Frau Auguste D., presented with emotional distress and delusions of infidelity/excessive jealousy, followed by cognitive symptoms. Being cognizant of this, in 2010 the Alzheimer's Association convened a research roundtable on the topic of NPS in AD. A major outcome of the roundtable was the founding of a Professional Interest Area (PIA) within the International Society to Advance Alzheimer's Research and Treatment (ISTAART). The NPS‐PIA has prepared a series of documents that are intended to summarize the literature and provide more detailed specific recommendations for NPS research. This overview paper is the first of these living documents that will be updated periodically as the science advances. The overview is followed by syndrome‐specific synthetic reviews and recommendations prepared by NPS‐PIA workgroups on depression, apathy, sleep, agitation, and psychosis.

[1]  G. Alexopoulos,et al.  Cornell scale for depression in dementia , 1988, Biological Psychiatry.

[2]  M. Folstein,et al.  Clinical diagnosis of Alzheimer's disease , 1984, Neurology.

[3]  L. Schneider Organising the language of Alzheimer's disease in light of biomarkers , 2010, The Lancet Neurology.

[4]  Denise C. Park,et al.  Toward defining the preclinical stages of Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer's Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[5]  J. Cummings,et al.  Positron emission tomography metabolic correlates of apathy in Alzheimer disease. , 2007, Archives of neurology.

[6]  Joseph B. Martin The integration of neurology, psychiatry, and neuroscience in the 21st century. , 2002, The American journal of psychiatry.

[7]  S. Reeves,et al.  Increased striatal dopamine (D2/D3) receptor availability and delusions in Alzheimer disease , 2009, Neurology.

[8]  Liat Ayalon,et al.  Effectiveness of nonpharmacological interventions for the management of neuropsychiatric symptoms in patients with dementia: a systematic review. , 2006, Archives of internal medicine.

[9]  Vijaya L. Melnick,et al.  Alzheimer’s Dementia , 1985, Contemporary Issues in Biomedicine, Ethics, and Society.

[10]  B. Pollock,et al.  The 5-HTTPR Polymorphism Confers Liability to a Combined Phenotype of Psychotic and Aggressive Behavior in Alzheimer Disease , 2001, International Psychogeriatrics.

[11]  M. Folstein,et al.  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 , 2011, Neurology.

[12]  L. Fratiglioni,et al.  Psychiatric history and related exposures as risk factors for Alzheimer's disease: a collaborative re-analysis of case-control studies. EURODEM Risk Factors Research Group. , 1991, International journal of epidemiology.

[13]  C. Caltagirone,et al.  Neuropsychiatric predictors of progression from amnestic-mild cognitive impairment to Alzheimer's disease: the role of depression and apathy. , 2010, Journal of Alzheimer's disease : JAD.

[14]  G. Alexopoulos,et al.  'Vascular depression' hypothesis. , 1997, Archives of general psychiatry.

[15]  M. Mesulam,et al.  From sensation to cognition. , 1998, Brain : a journal of neurology.

[16]  D. Jeste,et al.  Overview of depression and psychosis in Alzheimer's disease. , 1989, The American journal of psychiatry.

[17]  J. Cummings,et al.  Delusional thoughts and regional frontal/temporal cortex metabolism in Alzheimer's disease. , 2003, The American journal of psychiatry.

[18]  R. Mohs,et al.  Consortium to establish a registry for Alzheimer's disease (CERAD) clinical and neuropsychological assessment of Alzheimer's disease. , 2002, Psychopharmacology bulletin.

[19]  V. Pankratz,et al.  Prevalence of neuropsychiatric symptoms in mild cognitive impairment and normal cognitive aging: population-based study. , 2008, Archives of general psychiatry.

[20]  G. E. Alexander,et al.  Basal ganglia-thalamocortical circuits: parallel substrates for motor, oculomotor, "prefrontal" and "limbic" functions. , 1990, Progress in brain research.

[21]  J. Cummings Frontal-subcortical circuits and human behavior. , 1998, Archives of neurology.

[22]  R. Sapolsky,et al.  Glucocorticoids and hippocampal atrophy in neuropsychiatric disorders. , 2000, Archives of general psychiatry.

[23]  A. Alzheimer Uber eine eigenartige Erkrankung der Hirnrinde , 1907 .

[24]  N. Geschwind,et al.  A Human Cerebral Deconnection Syndrome , 1974 .

[25]  C. Reynolds,et al.  Imaging Alzheimer Pathology in Late-Life Depression With PET and Pittsburgh Compound-B , 2008, Alzheimer disease and associated disorders.

[26]  S. M. Sumi,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1991, Neurology.

[27]  J. Cummings,et al.  Validation of the NPI-Q, a brief clinical form of the Neuropsychiatric Inventory. , 2000, The Journal of neuropsychiatry and clinical neurosciences.

[28]  Faith M. Gunning-Dixon,et al.  Translational Research in Late-Life Mood Disorders: Implications for Future Intervention and Prevention Research , 2007, Neuropsychopharmacology.

[29]  R. Robinson,et al.  Double-blind treatment of apathy in patients with poststroke depression using nefiracetam. , 2009, The Journal of neuropsychiatry and clinical neurosciences.

[30]  S. Jaffe Neurology and psychiatry: closing the great divide. , 2000, Neurology.

[31]  G. Schellenberg,et al.  Impact of Sample Selection on APOE ∈4 Allele Frequency: A Comparison of Two Alzheimer's Disease Samples , 1996 .

[32]  Daniel Weintraub,et al.  Effectiveness of atypical antipsychotic drugs in patients with Alzheimer's disease. , 2006, The New England journal of medicine.

[33]  W. Hauck,et al.  Targeting and Managing Behavioral Symptoms in Individuals with Dementia: A Randomized Trial of a Nonpharmacological Intervention , 2010, Journal of the American Geriatrics Society.

[34]  J. Cummings,et al.  Frontal-subcortical circuits and human behavior. , 1993, Journal of psychosomatic research.

[35]  David Eidelberg,et al.  Serotonin Modulation of Cerebral Glucose Metabolism in Depressed Older Adults , 2009, Biological Psychiatry.

[36]  J. Cummings,et al.  Mild Cognitive Impairment is Associated With Characteristic Neuropsychiatric Symptoms , 2004, Alzheimer disease and associated disorders.

[37]  V. Pankratz,et al.  Depression, apolipoprotein E genotype, and the incidence of mild cognitive impairment: a prospective cohort study. , 2006, Archives of neurology.

[38]  Nick C Fox,et al.  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 , 2011 .

[39]  C. Lyketsos,et al.  Neuropsychiatric disturbance in Alzheimer's disease clusters into three groups: the Cache County study , 2001, International journal of geriatric psychiatry.

[40]  Jeannie-Marie S. Leoutsakos,et al.  The Neuropsychiatric Inventory-Clinician rating scale (NPI-C): reliability and validity of a revised assessment of neuropsychiatric symptoms in dementia , 2010, International Psychogeriatrics.

[41]  Yaakov Stern,et al.  Scales as outcome measures for Alzheimer's disease , 2009, Alzheimer's & Dementia.

[42]  G. Schellenberg,et al.  Impact of sample selection on APOE epsilon 4 allele frequency: a comparison of two Alzheimer's disease samples. , 1996, Journal of the American Geriatrics Society.

[43]  J. Cohen-Mansfield,et al.  An Observational Study of Agitation in Agitated Nursing Home Residents , 1989, International Psychogeriatrics.

[44]  P. Truax,et al.  Assessment of behavioral problems in dementia: the revised memory and behavior problems checklist. , 1992, Psychology and aging.

[45]  P. Tariot,et al.  A 5-month, randomized, placebo-controlled trial of galantamine in AD , 2000, Neurology.

[46]  G. Alexopoulos The Vascular Depression Hypothesis: 10 Years Later , 2006, Biological Psychiatry.

[47]  M M Mesulam,et al.  Large‐scale neurocognitive networks and distributed processing for attention, language, and memory , 1990, Annals of neurology.

[48]  B. Lawlor,et al.  A randomized trial of risperidone, placebo, and haloperidol for behavioral symptoms of dementia , 1999, Neurology.

[49]  J. Moossy,et al.  Neurochemical correlates of major depression in primary dementia. , 1990, Archives of neurology.

[50]  R. Sweet,et al.  Genetics of psychosis in Alzheimer's disease: a review. , 2010, Journal of Alzheimer's disease : JAD.

[51]  I M Wilkinson,et al.  Psychogeriatric Dependency Rating Scales (PGDRS) A Method of Assessment for Use by Nurses , 1980, British Journal of Psychiatry.

[52]  R. Marin,et al.  Apathy: a neuropsychiatric syndrome. , 1991, The Journal of neuropsychiatry and clinical neurosciences.

[53]  R. Hales,et al.  J Neuropsychiatry Clin Neurosci , 1992 .

[54]  David S. Miller,et al.  Neuropsychiatric symptoms in Alzheimer’s disease , 2011, Alzheimer's & Dementia.

[55]  J. Morris,et al.  The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer's disease , 2011, Alzheimer's & Dementia.

[56]  D. Paleacu,et al.  Quetiapine treatment for behavioural and psychological symptoms of dementia in Alzheimer's disease patients: a 6‐week, double‐blind, placebo‐controlled study , 2008, International journal of geriatric psychiatry.

[57]  David Eidelberg,et al.  Cholinergic modulation of the cerebral metabolic response to citalopram in Alzheimer's disease. , 2009, Brain : a journal of neurology.

[58]  W. Klunk,et al.  Imaging brain amyloid in Alzheimer's disease with Pittsburgh Compound‐B , 2004, Annals of neurology.

[59]  A. Heyman,et al.  The Consortium to Establish a Registry for Alzheimer's Disease (CERAD) , 1993, Neurology.

[60]  J. Morris,et al.  The Uniform Data Set (UDS): Clinical and Cognitive Variables and Descriptive Data From Alzheimer Disease Centers , 2006, Alzheimer disease and associated disorders.

[61]  R. Hu Diagnostic and Statistical Manual of Mental Disorders (DSM-IV) , 2003 .

[62]  C. Lyketsos,et al.  Prevalence of neuropsychiatric symptoms in dementia and mild cognitive impairment: results from the cardiovascular health study. , 2002, JAMA.

[63]  J. Overall,et al.  The Brief Psychiatric Rating Scale , 1962 .

[64]  M. Mesulam Principles of Behavioral and Cognitive Neurology , 2000 .

[65]  E. Helmes,et al.  Standardization and validation of the Multidimensional Observation Scale for Elderly Subjects (MOSES). , 1987, Journal of gerontology.

[66]  L. Schneider,et al.  A pilot randomized trial of carbamazepine for behavioral symptoms in treatment-resistant outpatients with Alzheimer disease. , 2001, The American journal of geriatric psychiatry : official journal of the American Association for Geriatric Psychiatry.

[67]  Nick C Fox,et al.  Revising the definition of Alzheimer's disease: a new lexicon , 2010, The Lancet Neurology.

[68]  H. Kranzler,et al.  Longitudinal, Expert, All Data Procedure for Psychiatric Diagnosis in Patients with Psychoactive Substance Use Disorders , 1994, The Journal of nervous and mental disease.

[69]  A. LaCroix,et al.  Exercise plus behavioral management in patients with Alzheimer disease: a randomized controlled trial. , 2003, JAMA.

[70]  E. Kokmen,et al.  Impact of referral bias on clinical and epidemiological studies of Alzheimer's disease. , 1996, Journal of clinical epidemiology.