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

Anatomical Functional Biochemical

Anatomical Functional Biochemical Presence of certain genes Premorbid personality Predisposing factors

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):1165-73.

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.

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):438-49.

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.

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

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.

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. 2005;13(7):624-7.

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

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

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