1. Neurobiology of BPSD Rajesh Tampi , MD Professor of Psychiatry
Case Western Reserve University School of Medicine

2. Anatomical
Functional
Biochemical

3. Anatomical Functional Biochemical Presence of certain genes
Premorbid personality
Predisposing factors

4. Neuropathology of BPSD
Frontal
Temporal
Neuritic plaques and neurofibrillary tangles
Farber NB, Rubin EH, Newcomer JW, et al. Increased neocortical neurofibrillary tangle density in subjects with Alzheimer disease and psychosis. Arch Gen Psychiatry. 2000;57(12):

5. Neuropathology of BPSD
Associated with delusional misidentification syndrome
Right frontal atrophy
Frontal
Forstl H, Besthorn C, Burns A, et al. Delusional misidentification in Alzheimer’s disease: a summary of clinical and biological aspects. Psychopathology. 1994;27(3-5):194-9.

6. Frontal, parietal and temporal cortical dysfunction
Psychotic symptoms
Frontal, parietal and temporal cortical dysfunction
Parietal
Frontal
Temporal
Mentis MJ, et al. Abnormal brain glucose metabolism in the delusional misidentification syndromes: a positron emission tomography study in Alzheimer disease. Biol Psychiatry. 1995;38(7):

7. Parietal Frontal Temporal
Delusional misidentification syndromes
Greater EEG delta-power over the right hemisphere
Parietal
Frontal
Temporal
Forstl H, Besthorn C, Burns A, et al. Delusional misidentification in Alzheimer’s disease: a summary of clinical and biological aspects. Psychopathology. 1994;27(3-5):194-9.

8. Neurochemical changes
Damage to:
Cholinergic neurons
Adrenergic systems
Serotonergic systems
Frontal and temporal cortex
Cummings JL, Back C. The cholinergic hypothesis of neuropsychiatric symptoms in Alzheimer’s disease. Am J Geriatr Psychiatry. 1998;6(2 Suppl 1):S64-78

9. Neurochemical changes
Associated with psychotic symptoms
Higher levels of NE in the substantia nigra
Lower 5-HT levels in the presubiculum
Zubenko GS, Moossy J, Martinez J, et al: Neuropathologic and neurochemical correlates of psychosis in primary dementia. Arch Neurol. 1991; 48:619–624.

10. Genetics
Depression is more common in first-degree relatives of depression
The heritability for psychotic symptoms is between 30% to 61%
Bacanu SA, Devlin B, Chowdari KV, et al. Heritability of psychosis in Alzheimer disease. Am J Geriatr Psychiatry ;13(7):624-7.

11. Genetics APOE APOE4 allele: earlier age of onset of symptoms
APOE2 allele: depressive symptoms
APOE4 allele: disorientation, agitation and motor disorder
APOE3 allele: anxiety and sleep disorders
Ballard C, Massey H, Lamb H, et al. Apolipoprotein E: non-cognitive symptoms and cognitive decline in late onset Alzheimer’s disease. J Neurol Neurosurg Psychiatry. 1997;63(2):273-4

12. Genetics Polymorphisms Serotonin (5-HT2A) receptor polymorphisms
Visual and auditory hallucinations
Dopamine receptor polymorphisms
Psychosis and agression
Sukonick DL, Pollock BG, Sweet RA, et al. The 5-HTTPR*S/*L polymorphism and aggressive behavior in Alzheimer disease. Arch Neurol. 2001;58(9):1425-8

13. Psychological aspects
Depressive symptoms
High premorbid levels of neuroticism
Meins W, Frey A, Thiesemann R. Premorbid personality traits in Alzheimer’s disease: do they predispose to noncognitive behavioral symptoms? Int Psychogeriatr. 1998;10(4):369-78