Disclosures Consultant Forest,Genentech,Lundbeck,Novarti - PDF document

2/27/2015 Depression In Major Neurocognitive Disorders: Early Marker Risk Factor Recognition and Treatment George T. Grossberg MD Samuel W. Fordyce Distinguished Professor Director, Geriatric Psychiatry Department of Neurology & Psychiatry St Louis University School of Medicine St Louis, MO. USA Disclosures Consultant ‐ Forest,Genentech,Lundbeck,Novarti s,Otsuka,Roche,Takeda Research Support ‐ Accera, Merck,Noven Safety Monitoring ‐ Merck, Newron OBJECTIVES Elucidate data on Depression as an early marker for AD Evidence for Depression as a risk ‐ factor for AD Discuss prevalence, diagnostic and treatment approaches for Depression in Major Neurocognitive Disorders 1

2/27/2015 Depression as an Early Marker for AD Timeline and Epidemiology of Psychiatric Symptoms in AD Agitative symptoms 100 Depressive symptoms Psychotic symptoms Other symptoms Agitation 80 Frequency, % of Patients Diurnal Rhythm 60 Irritability Depression Wandering Aggression Social 40 Withdrawal Mood Socially Anxiety Change Hallucinations Unacc. Paranoia 20 Suicidal Delusions Accusatory Ideation Sexually Inappropriate 0 ‐ 40 ‐ 30 ‐ 20 ‐ 10 0 10 20 30 Months Before/After Diagnosis Adapted from Jost BC, et al. J Am Geriatr Soc . 1996;44:1078 ‐ 1081; with permission. Change in Depression Symptoms During the Prodromal Phase of Alzheimer’s Disease (1) • Rush Religious Orders Study followed 917 older Catholic clergy for 13 years – 190 developed AD • Having more depressive symptoms at baseline was associated with increased incidence of AD and MCI Ref: Wilson RS, et al. Arch Gen Psych, April 2008; 65(4):437 ‐ 45 2

2/27/2015 Midlife vs Late ‐ Life Depressive Symptoms and Risk of Dementia:Differential Effects for AD and VaD • Retrospective cohort study ‐ 15,535 Kaiser Permanente members, N. California ‐ 6yr F/U • Depression in 14% @ midlife;9% late ‐ life;4% both • Dementia risk increased by 20% for midlife Depression; 70% for late ‐ life depression; 80% for both • Late ‐ life depression only>200% increase in AD risk;midlife + late ‐ life depression>300% increase in VaD R f B DE l A h G P hi 2012 History of Depression as a RF for AD • Case controlled design:294 pts with AD and 300 normal controls; mean age 78.5. • Found an odds ratio(OR) of 2.0 for depression occurring more than 10 years before AD symptoms; an OR of 0.9 for depression onset within 10 years of the onset of AD symptoms • Ref:Speck, CE et al: Epidemiology,1995 Does Depression Severity Influnce Risk for Dementia/AD? 3

2/27/2015 Depression Subtypes and 5 ‐ year Risk of Dementia and AD Population ‐ based cohort study in Spain of 451 non ‐ demented older • people, followed for 5 years Major depression (MD) and minor depressive disorder(MDDIS) were • looked at Late ‐ onset depressions(both MD and MDDIS) were associated with • increased dementia(hazard ratio[HR] =2.635 and HR =2.517) and AD (HR=6.262 and 4.208). 2 nd model>Only late ‐ onset depression with Executive Dysfunction • Syndrome (DEDS) increased the risk for BOTH dementia (Late ‐ onset MD with DEDS > HR=6.262) ; (Late ‐ onset MDDIS with DEDS > HR=4.208 & AD(late ‐ onset MD with DEDS > HR=7.807; Late ‐ onset MDDIS with DEDS>HR=6.099) Ref:Vilalta ‐ Franch J, et al:Int J Geriatr Psychiatry, 2013 • Depression and the Risk for Dementia—Impact of Depression Tx Early ‐ onset depression (before age 65) and recurrent depression may • constitute long ‐ term risk factors for development of dementia. Onset of more recent depression symptoms may reflect a prodromal • phase of dementia. Not clear if specific subtypes of depression correspond to specific • types of dementia. Long ‐ term treatment with anti ‐ depressants may decrease the risk of • developing some types of dementia, depending on the type of depressive disorder. Ref:Kessing,LV:Curr Opin Psychiatry, 2012. • Late ‐ life Depression as a Risk ‐ Factor for MCI or AD in 30 US Alzheimer’s Disease Centers + Prospective study ‐ 5,607 subjects with normal cognition and 2500 subjects with MCI, followed for 6 years. + Always depressed throughout study had increased risk of progression from normal to MCI (RR=2.35); normal subjects depressed at first visit but improved had a lower risk (RR=1.40). + Always depressed had modest increased risk of progression from MCI to AD (RR=1.21) + Effect of recent depression did not differ by antidepressant treatment, APOE ‐ 4 status, or type of MCI. +Overall, late ‐ life depression is a strong risk factor for normal subjects progressing to MCI. ++ Ref:Steenland, K et al:J Alzheimer’s Dis, 2012. 4

2/27/2015 Depression In Dementia ‐ Prevalence • + AD…. 20 ‐ 40% • + PDD…. 30 ‐ 50% • + VaD…. 35 ‐ 50% • + DLB…. 50 ‐ 60% • Ref: Ballard,et al 1996;Brodaty, 1996;Zubenko et al 2003;Borroni et al, 2008. Diagnosing Depression In Dementia • + Can be reliably diagnosed • + GDS useful for MMSE scores > 10 • + CSDD useful for advanced dementia • + Depression symptoms often fluctuate (bright affect with tearfullness later in day) • + Flat affect ‐ Rarely smiles • + Irritability/verbal & physical aggression/ isolation/social withdrawal • Ref: Adapted from Desai & Grossberg ‐ P hi t i C lt ti i LTC J H ki P Diagnosing Depression In Dementia • + Key sign is flat affect – rarely smiles • + Sad,tearful,isolative,easily discouraged, sleep and appetite disturbance, vague somatic complaints, hopeless, worthless,helpless (“why don’t you just kill me”, guilty (“I am a burden”), a wish to die • + Depression can accelerate cognitive decline in dementia and can be mis ‐ diagnosed as dementia, such as AD. R f D i & G b 2010 5

2/27/2015 Diagnosing Depression In Dementia • + May say ‘no’ when asked if depressed but may say ‘yes’ to being bored,lonely, or useless. • + Advanced dementia ‐ agitation, wanting to go home, yelling: “help me, help me” • + Abrupt cognitive or behavioral change in AD may be triggered by depression (delirium also needs to be considered) • + ‘Trust the family’ re: suspicion of depression • Ref: Desai & Grossberg, 2010. Depression In Dementia ‐ Treatment • + If in doubt, treat. Depression is highly treatable • + Depression workup: PE/Neuro exam; screening tool (GDS; CSDD); Look for sources of pain; Bloodwork:CMP,CBC,TSH,B12/Folate, Vitamin D levels. UA. EKG if warranted. • + The same antidepressants we use in non ‐ demented elderly with MDD are effective here • + Avoid anticholinergic antidepressants Depression In Dementia ‐ Treatment • + “Start low and go slow, but go” • + Pick anti ‐ depressant based on what side ‐ effects we want or do not want in a particular patient e.g. activating vs calming • + Allow 4 ‐ 6, up to 8 weeks or > for optimal benefits • + Apathy is not depression ‐ psychostimulants may be useful • + Electro ‐ convulsive Therapy (ECT) is safe, works quickly, and may be life ‐ saving in / h i d i 6

2/27/2015 Conclusions • Depression as an early marker and possible risk ‐ factor for AD/dementia is receiving a lot of support. • Diagnosis of depression in dementia and aggressive treatment is vital to minimize excess morbidity and mortality and to improving the quality of life of patients and caregivers. 7