Dementia-A disease with no hope?

Dr Shahul Hameed MRCPUK,FAMS

Consultant Neurologist National Neuroscience Institute(SGH)

Memory Disorders

► Singapore --fastest ageing population

► 15-20% of total population--aged above 65 in 2030

► Prevalence of dementia/cognitive impairment --2-14%

► Malay(9.4%) Indian (8.8%) Chinese(4.2%)

DSM-1V Criteria for Dementia

► Amnesia Gradually

► And declines in one of the following domains

► Aphasia Communication problem

► Apraxia Motor task problems

► Agnosia Problems in recognising

► Executive dysfunctioning— Tasks which was not a problem before

► As a result becoming less independent in self care,home care and community.

ADL

►4 ADLs gets affected in early dementia:(Peres

et al J Am Geriatr Soc.)

►1.Communication

►2.Planning an outing and completing

►3.Using medications safely

►4.Handling money appropriately

Case Study

►67 yrs old lady Retired school teacher

►Lives with her daughter

►Had ischemic stroke 5 years ago-Right Hemiplegia with full functional recovery

►Had Minor short term memory deficits and word finding problems since her stroke

► Daughter notices 2 year history of worsening memory leading to poor personal hygiene and housekeeping.

► Very apathetic,not socializing like before

► She had lost her way in her neighbourhood twice.

► Pmhx: HPT,Hyperlipids.

► Exam: Neuropsych-- MMSE-27/30(1/3 delayed recall,2/3 on 3 step command)

► FAB- 8/18.—Points lost in abstraction,verbal fluency and conflicting instructions tasks.

► Her clock drawing was impaired.

►Diagnosis: Vascular Dementia

►Followup:

►Acetylcholinesterase inhibitor

►Next 3 months improvement in her intiative for activities of daily living and social outings—Family feels she has improved

VCI

► VCI- Heterogenous group of cognitive disorders related to small and large cerebral vessel disease

► CIND—VASCULAR DEMENTIA

► VaD: Multiinfarct Dementia

► Post stroke Dementia

► Strategic infarct Dementia

► Subcortical Vascular Dementia(Binswanger’s Disease).

► Prevalence of post stroke dementia 14% -32% (Barba

et al,stroke. Henon et al Neurology.)

► VCI-Pattern of cognitive deficits varies considerably

► Single strategic large vessel infarct have specific cognitive profile.

► while subcortical lesions-Dysexecutive syndromes—Slow information processing speed,emotional lability.

► Impaired ability to plan,organize,intiate and shift between tasks.

► MMSE are often insensitive to these abnormalities (Royall et al J Am Geriatr Soc )

► Dysexecutive type of impairment rapidly apparent on FAB (Dubois et al Neurology)

► The clinical course of post stroke dementia is difficult to

predict with upto one-third of people having a change in their diagnostic category(NCI,CIND,DEMENTIA) within one year after stroke ( Tham et al,J,Neurol Sci )

Risk factors for progression to VCI in stroke :

Age

Cognitive reserve before the stroke

Polypharmacy

Hypotension during acute stroke

Depression

Strategic infarcts like temporal lobe

(Del Ser et al,Stroke. Brodaty et al Am J Geriat Psychiatry)

►Treatment:

►Minimize the risk of future strokes

►Control vascular risk factors

►Cholinesterase inhibitors

►NMDA Antagonist-Memantine

►Selective serotonin reuptake inhibitors has shown to improve executive dysfunction in VCI and depressive symptoms in AD (Opler et

al J Clin Psych.)

Case Study ►60 yrs Chinese Housewife

►Presented with- Word finding difficulty

►Memory problems

►Informant-Husband noticed-Progressive problems for past 2 years

►Difficulties in conversation

►Difficulties in cooking

►Misplacing things in house

►PmHx: HPT,Asthma

►Examination: Neuroexam- Normal

►Neuropsychology: MMSE-22/30

►Impairment in Language-Anomia

►Impaired Semantic Verbal fluency

►Impairment in executive function

►ADLs-- Well preserved,Still drives car to go and play mahjong with her friends. Goes to movies(but when asked about the story line-can’t recollect).

►MRI BRAIN

Focal Atrophy of left temporal lobe and

Left Hippocampus.

►FDG-PET SCAN

Asymetrical decreased glucose

Metabolism in left temporal

Lobe

Normal metabolism in frontal

Lobes,basal ganglia and

Occipital lobes.

►CSF Routine Exam- Normal

CSF Biomarkers Beta 42 amyloid– LOW

Phospharylated Tau- High

Total Tau– High.

Diagnosis: Alzheimers Disease Dementia

(Logopenic Progressive Aphasia)

Followup: Acetylcholinesterase inhibitor

Cognitive and Global function-stable for past 4 years.

►Logopenic progressive aphasia (LPA) is a form of progressive primary aphasia characterized by slow speech and impaired syntactic comprehension and naming.

► It is similar to Wernickes aphasia and is associated with atrophy to the left posterior temporal cortex and inferior parietal lobe.

►An atypical form of AD is the most common cause of logopenic progressive aphasia.

Amyloid hypothesis

Biomarkers ►Imaging: Volumetric MRI

► FDG-PET Brain

► PiB PET Scan

►CSF: Beta 42 amyloid

► Total Tau

► Phosphorylated Tau

Dynamic biomarker model Clifford jack et al

Case Study

►Mr L C M 65 years old Working Executive

►Presented with 1 year history of memory problems

►Needs to make lists when goes to shopping (not before)

►Occasionally misplaces objects at home

►Wife Complains: ‘He forgets details of conversation we have’

►He has diifuculty in remembering numbers

Case Study

► Sometimes takes time to recall words during conversation-self reported

► Mr LCM functionally independent,drives to work,sometimes plays organ in church,little exercise.

► Past Medical History : HPT on Norvasc : Insomnia on Diazepam

Regularly

► Family History: Mother died of AD at age 80 ►

Case Study

► Clinical Exam- Normal

► Neuropyschology tests:

► MMSE 22/30

► MOCA 25/30

► Verbal memory & Visual memory tasks—Impaired

► Attention,Language,Executive Function,Visuoconstruction,Visuomotor speed,NPI,ADCS ADL inventory –All Unimpaired.

Case Study

►Basic blood tests all Normal

►MRI Brain –Normal

►? Diagnosis

MCI

►Subjective complaint of Memory loss

►Gradual in onset -6 months

►Objective impairment of memory

►Generally preserved other cognitive domains

►Preserved basic daily day to day function

►Not Demented

►

Copyright restrictions may apply.

Petersen, R. C. et al. Arch Neurol 2009;66:1447-1455.

Current flowchart for the diagnosis of mild cognitive impairment (MCI) and its subtypes

Donepezil delays progression to AD in MCI subjects with depressive symptoms. Lu PH; Edland SD; Teng E; Tingus K; Petersen RC; Cummings JL

Neurology. 2009 Jun 16;72(24):2115-21.

► Results suggest that depression is predictive of progression from amnestic mild cognitive impairment (aMCI) to Alzheimer disease (AD) and treatment with donepezil delayed progression to AD among depressed subjects with aMCI. Donepezil appears to modulate the increased risk of AD conferred by the presence of depressive symptoms

Physical Exercise ► Effect of physical activity on cognitive function in older adults at risk for Alzheimer

disease: a randomized trial. ► Lautenschlager NT; Cox KL; Flicker L; Foster JK; van Bockxmeer FM; Xiao J; Greenop KR; Almeida ► JAMA. 2008 Sep 3;300(9):1027-37. ► ► CONTEXT: Many observational studies have shown that physical activity reduces the risk of cognitive decline;

however, evidence from randomized trials is lacking. OBJECTIVE: To determine whether physical activity reduces the rate of cognitive decline among older adults at risk. DESIGN AND SETTING: Randomized controlled trial of a 24-week physical activity intervention conducted between 2004 and 2007 in metropolitan Perth, Western Australia. Assessors of cognitive function were blinded to group membership. PARTICIPANTS: We recruited volunteers who reported memory problems but did not meet criteria for dementia. Three hundred eleven individuals aged 50 years or older were screened for eligibility, 89 were not eligible, and 52 refused to participate. A total of 170 participants were randomized and 138 participants completed the 18-month assessment. INTERVENTION: Participants were randomly allocated to an education and usual care group or to a 24-week home-based program of physical activity. MAIN OUTCOME MEASURE: Change in Alzheimer Disease Assessment Scale-Cognitive Subscale (ADAS-Cog) scores (possible range, 0-70) over 18 months. RESULTS: In an intent-to-treat analysis, participants in the intervention group improved 0.26 points (95% confidence interval, -0.89 to 0.54) and those in the usual care group deteriorated 1.04 points (95% confidence interval, 0.32 to 1.82) on the ADAS-Cog at the end of the intervention. The absolute difference of the outcome measure between the intervention and control groups was -1.3 points (95% confidence interval,-2.38 to -0.22) at the end of the intervention. At 18 months, participants in the intervention group improved 0.73 points (95% confidence interval, -1.27 to 0.03) on the ADAS-Cog, and those in the usual care group improved 0.04 points (95% confidence interval, -0.46 to 0.88). Word list delayed recall and Clinical Dementia Rating sum of boxes improved modestly as well, whereas word list total immediate recall, digit symbol coding, verbal fluency, Beck depression score, and Medical Outcomes 36-Item Short-Form physical and mental component summaries did not change significantly.

► CONCLUSIONS: In this study of adults with subjective memory impairment, a 6-month program of physical activity provided a modest improvement in cognition over an 18-month follow-up period.

Case Study

► A 52-year-old male tax accountant began to embezzle money at work, regularly withdrawing $150 from his office account in order to buy pornography on the Internet.

► Around the time that he was caught by his supervisor, female employees complained that the patient stared inappropriately at them and often made rude comments about their breasts or weight.

► His work had dramatically deteriorated, and rather than working on his accounts, he spent most of the day downloading pornography onto his computer.

► He was fired from the job but made no attempts to find a new job.

Case Study

► His wife and children reported that over the past year he had lost interest in them and watched television without speaking when at home.

► ► He developed a strong desire for ice cream and

gained 20 lbs.

► His manners deteriorated, and he stuffed his mouth, often choking at the dinner table.

► He insisted on eating food on his plate in a specific order, often with his hands.

Case Study

►Neuroexam: No focal deficits

►MMSE: 22/30

►FAB : 9/18

►Blood and CSF-NAD

►MRI BRAIN:

►

FrontoTemporal Degeneration/FTD

bvFTD – behavioral variant FTD

Semantic Variant FTD

PNFA FTD – Progressive non-fluent aphasia

►Depends on which side and site affected first

►Can be confused with PSY case in early stage

► Third most common cause of degenerative dementia, accounting for 3% to 16% of all dementias

► FTD is more common than AD in patients younger than 60 years, the prevalence of FTD is close to that of AD in patients between ages 60 and 70

► Median survival time from first symptom is shorter in FTD than in AD(ranging from 2 to 8 years) bvFTD - 6 to 8 years SV - 8 to 12 years PNFA - 11 to 12 years

Ratnavalli E, Brayne C, Dawson K, Hodges JR. The prevalence of frontotemporal dementia.

Neurology 2002;58(11):1615–1621.

FrontoTemporal Degeneration/FTD

Case Study

► 70 yr Lady –Alzheimer’s Disease

► On Donepezil

► Caregiver—Husband and Maid

► Pt Complains –Husband having affair with maid

► Pinches him until he gets bruised in hand

► Gets very intimate and kisses him often in public

BPSD

►1.Apathy

►2.Agitation & Aggressivity

►3.Anxiety & Depression

►4.Delusions & Hallucinations

►5.Irritability

►6.Night time behaviors

►7.Disinhibition

PDA

Relative frequencies of the main dementias

DLB with

AD 12%

Pure vascular

dementia 5%

Alzheimer’s disease

Vascular dementia

Dementia with Lewy bodies

Frontotemporal dementia

Other dementias white matter dementias

subcortical (secondary) dementias

transmissible encephalopathies

Gearing et al (1995); Kosunen et al (1996); Nagy et al (1998)

Mixed

vascular

dementia

and AD 10%

Pure DLB 3%

60%

5% 5%

Aetiology Reversible Irreversible

Hypothyroidism Vitamin B12 Deficiency Alcohol related-Korsakoffs NPH Syphilis Toxins Metabolic Neoplasms Subdural hematomas

Alzheimers disease Vascular dementia Fronto temporal dementia Dementia with Lewy Body CJD.

HOPE ► Even in the inevitable moments when all seems hopeless, men know that

without hope they cannot really live, and in agonizing desperation they cry for the bread of hope.

► MARTIN LUTHER KING JR., A Testament of Hope

THANK YOU