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

2/27/2015 1 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

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Depression as an Early Marker for AD

Timeline and Epidemiology

• f Psychiatric Symptoms in AD

Adapted from Jost BC, et al. J Am Geriatr Soc. 1996;44:1078‐1081; with permission.

Months Before/After Diagnosis Frequency, % of Patients 100 80 60 40 20

Agitation Diurnal Rhythm Irritability Wandering Aggression Hallucinations Mood Change Socially Unacc. Delusions Sexually Inappropriate Accusatory Suicidal Ideation Paranoia Depression Anxiety Social Withdrawal Agitative symptoms Depressive symptoms Psychotic symptoms Other symptoms

‐40 ‐30 ‐20 ‐10 10 20 30

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

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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
• ccurring 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?

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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).

• 2nd 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.

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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

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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

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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.