How to diagnose

Mild Cognitive Impairment

Paulus Anam Ong Memory Clinic - Hasan Sadikin Hospital Bandung Padjadjaran University - Indonesia

Outline of Presentation
Introduction Aging in Indonesia Progression of normal aging to MCI Early detection is the main role  Clinical Diagnostic of MCI Definition of MCI Clinical diagnostic of MCI MMSE CDR GDS


Conclusion

Aging in Indonesia
(WHO, 1998)
60000 50000
N (1000s) 40000

80+ 75-79 65-74

30000 20000 10000 0 1997 2025 2050

Indonesia
 The 4th populous elderly after China, India and South America  We will encounter large numbers of dementia cases in the future  Massive medical, social, and economic problems in the future
.

Progression of normal aging to dementia

Brain Aging
Normal Cognition
R e v e r s i b l e

Prodromal Dementia

Mild Cognitive Impairment

Stable or Reversible Impairment

Dementia

Other Dementias

Alzheimers Disease

Vascular Dementia

Progression of normal aging to dementia A minority of persons diagnosed with MCI remain stable or improve over time  The majority of declining MCI patients convert to AD, besides mixed with vascular and other dementia


Golumb J, Kluger A, Ferrsis SH. Mild Cognitive Impairment: Identifying and treating the earliest stage of Alzheimer s disease

Early detection of MCI cases is the main role Correct diagnosis in its early stages can be: Beneficial of treatment Prevent costly and inappropriate treatment resulting from misdiagnosis Give patients and families time to prepare for the challenging financial, legal, and medical decisions that may lie ahead.

Definition of MCI
   

Memory Complaints confirmed by an informant Normal activities of daily living General cognitive preserved Abnormal memory for age and education norms (1,5 SD below normative values ) Not demented

Petersen et al (1999) Arch Neurol 56,303-308

MCI Tenets :
  

Not all MCI represent AD All AD patients go through an MCI stage AD symptoms progress from MCI to greater severity of dementia Conversions ( MCI to AD ) is a clinical construct

inconsistent with pathology

 

Clinical methods accurately identify MCI

AD

Quality of clinical information ( informants ) and labeling threshold of clinician determines diagnosis

Clinical Diagnosis of MCI

Diagnosis of MCI requires an informant based history documenting a meaningful deterioration in cognitive status in daily functioning  Two commonly used rating scales


Clinical Dementia Rating (CDR) Global Deterioration Scale (GDS)

MCI Clinical Assessment

As a part of dementia assessment:  Careful history from family member / collateral source (key element) and from patient  Physical / neurological examination  Evaluation of behavior and mood

Clinical approach :


General medical history

   

CCVD and risk factor Endocrine disorders Chronic infections Life style

 

General neurologic history Specific conditions Which could be responsible for dementia
 

Head trauma SOL intracranial

Clinical approach :


Psychiatric history :
 

Pure psychiatric disorders Cognitive impairment associated with psychiatric diseases




Toxic, nutritions and drug history

Family history
  

Dementia Down s syndrome Degenerative diseases

Clinical approach :


General physical examination :

  

Vital signs Risk factor for vascular events Metabolic and endocrine

Neurological examination
 

Focal deficit Abnormalities of muscle tone, movement or primitive reflexes

Neuropsychological examinations
 

Minimental State Examination ( MMSE ) : u 24 Clinical Dementia Rating Scale ( CDR ) 0,5
     

Memory Orientations Judgment and problem solving Community affairs Home and hobbies Personal care

Global Deterioration Scale ( GDS ):stage 2-3 2-

Mini Mental Status Examination (MMSE)

Mini Mental Status Examination (MMSE)



Screening test to provide brief, objective measure of cognitive function. Administered in 10-15 minutes, scores 10range from 0 to 30

MMSE: Different cognitive domains tested

Questions grouped into seven categories:  Orientation to time 5 points  Orientation to place 5 points  Registration of three words 3 points  Attention and calculation 5 points  Recall of three words 3 points  Language 8 points  Visual construction 1 point

PEMERIKSAAN STATUS MENTAL MINI (MMSE)

POKDI FUNGSI LUHUR PUSAT (modifikasi FOLSTEIN)

No

Tes ORIENTASI Sekarang (tahun), (musim), (bulan), (tanggal), hari apa? Kita berada dimana? (negara), (propinsi), (kota), (rumah sakit), (lantai/kamar) REGISTRASI Sebutkan 3 buah nama benda ( Apel, Meja, Koin), tiap benda 1 detik, pasien disuruh mengulangi ketiga nama benda tadi. ATENSI DAN KALKULASI Kurangi 100 dengan 7. Nilai 1 untuk tiap jawaban yang benar. Hentikan setelah 5 jawaban. Atau disuruh mengeja terbalik kata WAHYU

Nilai Nilai mak 5 5 -----

1 2

---

---

PEMERIKSAAN STATUS MENTAL MINI (MMSE)

MENGINGAT KEMBALI (RECALL) 5 Pasien disuruh menyebut kembali 3 nama benda di atas BAHASA Pasien disuruh menyebutkan nama benda yang ditunjukkan ( pensil, buku) Pasien disuruh mengulang kata-kata: namun, tanpa, bila Pasien disuruh melakukan perintah: Ambil kertas ini dengan tangan anda, lipatlah menjadi dua dan letakkan di lantai. Pasien disuruh membaca dan melakukan perintah Pejamkanlah mata anda Pasien disuruh menulis dengan spontan Pasien disuruh menggambar bentuk di bawah ini Total 3 ---

6 7 8 9 10 11

2 1 3 1 1 1 30

---------------

Penilaian MMSE
Nilai: 24 -30: Tidak ada gangguan kognitif 17 -23: Probable gangguan kognisi 0 - 16: Definite gangguan kognisi

Good points of the MMSE

    

Most widely accepted screening test Good internal consistency Good test-retest reliability testHigh validity: good sensitivity and specificity Correlates well with other screening tests e.g. clock drawing test and Short Blessed test Can be used for diagnostic, follow up, measurement of therapeutic outcome

Correlation between ADL and MMSE

An integrated approach to the management of AD. Eur J Neurol.5 (suppl 4). S9-17

Limitation
 Confounded by age, education and culture.
Highly educated people with obvious dementia may score 27 or above (ceiling effect) Non demented subjects with modest educational attainment may score as low as 24 (floor effect)

 Can not be used as a single tool for diagnosis and it has to be interpreted within context of clinical history and examination

Conclusions from the MMSE

Useful in quantitatively estimating the severity of cognitive impairment ...in serially documenting cognitive change

Clinical Dementia Rating (CDR)

Clinical Dementia Rating (CDR)



   

SemiSemi-structured interview with the patient/subject and a well-informed wellcollateral source (informant). For diagnosis, staging, and changes (for clinical trial) More than 90% sensitivity and specificity. Validated against neuropathology information (Morris et al, 1988) One of the Gold Standard of Global rating of dementia in trial of patients with AD

Advantages of CDR
     

Face validity: measures decline relative to the validity: individual that interferes with usual functions Multidimensional Clinically meaningful, even when neuropsychological test is normal Avoids confounds factors e.g. education, age; age; practice effects that affect cognitive tests Less affected by ceiling and floor effects Reliable

Morris JC, Clinical Dementia Rating, 3rd Asia-Pacific Regional Meeting of !WGH, Bangkok 24th -26th March 2004

Disadvantages of CDR

Rely on availability of a good collateral source (eg. caregiver) (eg. Interviews are time-consuming timecompared to brief cognitive tests Require clinical judgment

Morris JC, Clinical Dementia Rating, 3rd Asia-Pacific Regional Meeting of !WGH, Bangkok 24th -26th March 2004

Clinical Dementia Rating (CDR)

Provides assessment of 6 domains / categories: 3 cognitive + 3 functional domains.  Cognitive domains: 1. Memory 2. Orientation 3. Judgment and problem solving ability  Functional domains: 4. Community affairs 5. Home and hobbies 6. Personal care.

Clinical Dementia Rating

Impairment
0
None

0.5
Questionable

1
Mild

2
Moderate

3
Severe

Memory Orientation Judgment and problem solving Community Affairs Home & Hobbies Personal Care

Clinical Dementia Rating

None 0 Memory No memory loss, or slight inconsiste nt forgetfulness Questionable 0.5 Consistent slight forgetfulnes; partial recollection of events; benign forgetfulness Mild 1 Moderate 2 Severe 3

Moderate memory lose; more marked for recent events; defect interferes with everyday activities

Severe memory loss; only highly learned material retained, new material rapidly lost Usually disoriented to time, often to place

Severe memory loss; only fragments remain

Orientation

Fully oriented

Fully oriented except for slight difficulty with time relationship

Some difficulty with time relationship; oriented for place& person at examination, but may have geographic disorientation

Oriented to person only

Clinical Dementia Rating

None 0 Judgement and problem solving Solves everyday problems and handles business and financial affairs well; judgement good in relation to past performance Independent function at usual level in job, shopping, and volunteer and social groups Questionable 0.5 Slight impairment in solving problems, similarities and differences Mild 1 Moderate 2 Severe 3

Moderate difficulty in handling problem, similarities and differences; social judgement usually maintained

Severely impaired in handling problems, similarities and differences; social judgement usually impaired

Unable to make judgements or solve problems

Community affair

Slight impairment in these activities

Unable to function independently at these activities although may still be engaged in some; appears normal to causal inspection

No pretense of independent function outside home. Appears well enough to be taken to functions outside a family home

No pretense of independent function outside home. Appears too ill to be taken to functions outside a family home

Clinical Dementia Rating

None 0 Home and hobbies Life at home, hobbies and intellectual interest well maintained Questionable 0.5 Life at home, hobbies and intellectual interests slightly impaired Mild 1 Moderate 2 Severe 3

Mild but definite impairment of function at home; more difficult chores abandoned; more complicated hobbies and interest abandoned Needs prompting

Only single chores preserved; very restricted interest, poorly maintained

No significant function in home

Personal care

Fully capable of self-care

Requires assistance in dressing, hygiene, keeping of personal effects

Requires much help with personal care; frequent incontinence

Morris JC,. Neurologly 1993; 43:2412-14(20)

CDR


Diagnosis

Three classification
No dementia = CDR 0 Uncertain dementia = CDR 0.5 (questionable dementia / MCI) Dementia
 CDR

0.5  CDR 1  CDR 2  CDR 3

= = = =

very mild dementia mild dementia moderate dementia severe dementia

Definition of CDR 0.5



..for subjects who are neither clearly demented nor healthy. Many in this group have syndromes compatible with the benign senescent forgetfulness of Kral while others probably have normal cognitive function but may be mildly depressed or concerned over minor forgetfulness. Still others are probably in an early stage of SDAT Hughes et al. Brit J Psychiat 1982;140;566-572

Morris JC, Clinical Dementia Rating, 3rd Asia-Pacific Regional Meeting of !WGH, Bangkok 24th -26th March 2004

Global Deterioration Scale GDS

Global Deterioration Scale

       

A seven-point rating scale sevenStage 1: normal cognitive capacity Stage 2: normal aging Stage 3: mild memory impairment (MCI) Stage 4: Mild AD Stage 5: Moderate AD Stage 6:Moderately severe AD Stage 7: Severe AD

Global deterioration scale

Clinical Characteristics GDS Stage Clinical Characteristics

1 No Subjective complaints of memory deficit Normal No memory deficit evident on clinical interview 2 Subjective complaints of memory deficit, Normal Most frequently in the following areas: aging  forgetting where one has placed familiar objects  forgetting names one formerly knew well No objective evidence of memory deficits on clinical interview No objective deficit in employment or social situations Appropriate concern with respect to symptomatology

Global deterioration scale

Clinical Characteristics GDS Stage 3 Clinical Characteristics

Earliest subtle deficits Manifestations in more than one of the following areas:  patient may have become lost when traveling to an unfamiliar location Mild memory  Co-workers become aware of patients relatively poor performance impairme  Word and name finding deficit become evident to intimates nt  Patient may read a passage or book and retain relatively little material  Patient may demonstrate decrease facility for remembering names upon introduction to new people  Patient may have lost or misplaced an object of value  Concentration deficit may be evident on clinical testing Objective evidence of memory deficit obtained only with an intensive interview Deceased performance in demanding employment and social setting Denial begins to become manifest in patients Mild to moderate anxiety frequently accompanies symptoms

Global deterioration scale

Clinical Characteristics GDS Stage 4 Clinical Characteristics

Clear-cut deficit on careful clinical interview Deficit manifest in following areas: Mild AD  Decrease knowledge of current and recent events  May exhibit some deficit in memory of ones personal history  Concentration deficit elicited on serial subtractions  Decreased ability to travel, handle finances, etc  Frequently no deficit in the following areas:  Orientation of familiar persons and faces  Ability to travel to familiar locations nability to perform complex task  Denial is dominant defence mechanism  Flattering of affect and withdrawal from challenging situation occur

Global deterioration scale

Clinical Characteristics GDS Stage 5 Clinical Characteristics

Patient can no longer survive without some assistance Patient is unable during interview to recall a major relevant aspect of their current life. For example: Moderate  Their address or telephone number for many years AD  The names of closes members of their family (e.g grandchildren)  The name of the high school or college from which they graduated Frequently some disorientation to time (date, day of the week, season, etc) or to place An educated person may have difficulty counting back from 40 by for fours or from 20 by twos Person at this stage retain knowledge of many major facts regarding themselves and others They invariably know their own names and generally know their spouses and childrens names They require no assistance with toileting or eating, but may have difficulty choosing the proper clothing to wear

Global deterioration scale

Clinical Characteristics GDS Stage 6 Clinical Characteristics

May occasionally forget the name of the spouse upon whom they are entirely dependent for survival Moderately Will be largely unaware of all recent events and experiences in their lives severe Retain some knowledge of their surroundings; the yea, the season etc AD May have difficulty counting by ones from 10, both backward and sometimes forward Will require some assistance with activities of daily living  May become incontinent  Will require travel assistance but occasionally will be able to travel to familiar location Diurnal rhythm frequently disturbed Almost always recall their own name Frequently continue to be able to distinguish familiar from unfamiliar persons in their environment

Global deterioration scale

Clinical Characteristics GDS Stage 6 Clinical Characteristics

Personality and emotional changes occur, these are quite variable and include: Moderately  Delusional behaviour (eq, patients may accuse their spouse of being an imposter; may talk to imaginary fiqures in the environment, or to severe their own reflection in the mirror) AD  Obsessive symptoims (eg. Person may continually repeat simple cleaning activities)  Anxiety symptoms, agitation, and even previously non-existent violent behaviour may occur  Cognitive abulia (eg. Loss of willpower because an individual can not carry a thought long enough to determine a purposeful course of action)

Global deterioration scale

Clinical Characteristics GDS Stage 7 Clinical Characteristics

All verbal abilities are lost over the course of this stage Early in this stage words and phrases are spoken but speech is very circumscribed Moderately Later there is no speech at all- only babbling severe Incontinent of urine, requires assistance toileting and feeding AD Basic psychomotor skill (eq, abililty to walk), are lost with the progression o this stage (sambunga The brain appears to no longer be able to tell the body what to do n) Generalized and cortical neurological signs and symptoms are frequently present
Reisberg B, Ferris FH, de Lean MJ et al. The global deterioration scale for assessment of primary degenerative dementia

The best diagnostic test is a careful history and physical and mental status examination by a physician with a knowledge of and interest in dementia and the dementing disease. Such an evaluation is time consuming, but nothing can replace it
Differential diagnosis of dementing diseases.NIH Consensus Statement. JAMA 1987, 258:3411-3416 258:3411-

Conclusion
1. Early detection and correct diagnosis in early stages can be beneficial of:
Treatment efficacy Preventing costly and inappropriate treatment resulting from misdiagnosis Giving patients and families time to prepare for the challenging financial, legal, and medical decisions that may lie ahead

Conclusion
2. The best diagnostic test is a careful history, physical and mental status examination by a physician with a knowledge of and interest in dementia and the dementing disease. Such an evaluation is time consuming, but nothing can replace it

Dementia, operation definition

Syndrome of multiple acquired cognitive deficits that sufficient to interfere with everyday activities

Dementia, diagnostic criteria

NINCDSNINCDS-ADRDA and DSM-IV criteria DSM-

(any two of the five below) (memory +any one below)

1. Memory impairment * 2. Aphasia (language disturbance) 3. Agnosia (impaired recognition/knowledge) 4. Apraxia (disability in performance of previously learned skills or tasks) 5. Executive dysfunction

Laboratory testing
 Urinalysis  Complete blood count, ESR  Liver enzymes  BUN, creatinin  Electrolytes, blood glucose  Vitamin B12, folic acid  TSH, free thyroid index  Syphilis serology, HIV testing, ApoE?

SKALA DEPRESI GERIATRIK 15

Pilihlah jawaban yang paling tepat, yang sesuai dengan perasaaan anda dalam satu minggu terakhir.
1. Apakah anda sebenarnya puas dengan kehidupan anda? 2. Apakah anda telah meninggalkan banyak kegiatan dan minat atau kesenangan anda? 3. Apakah anda merasa kehidupan anda kosong? 4. Apakah anda sering merasa bosan? 5. Apakah anda mempunyai semangat yang baik setiap saat? 6. Apakah anda takut bahwa sesuatu yang buruk akan terjadi pada anda? YA Tidak 7. Apakah anda merasa bahagia untuk sebagian besar hidup anda?Ya TIDAK YA YA YA Tidak Tidak Tidak Ya TIDAK

Ya TIDAK

SKALA DEPRESI GERIATRIK 15

8. Apakah anda sering merasa tidak berdaya YA 9. Apakah anda lebih senang tinggal dirumah daripada keluar dan mengerjakan sesuatu yang baru? YA 10.Apakah anda merasa mempunyai banyak masalah dengan daya ingat anda dibanding kebanyakan orang? YA 11. 11. Apakah anda pikir bahwa hidup anda sekarang ini menyenangkan Ya 12. Apakah anda merasa tidak berharga seperti perasaan anda saat ini? YA 13. Apakah anda merasa anda penuh semangat? Ya 14. Apakah anda merasa bahwa keadaan anda tidak ada harapan YA 15. Apakah anda pikir bahwa orang lain lebih baik keadaannya dari pada anda? YA Tidak Tidak Tidak TIDAK Tidak TIDAK Tidak Tidak

Pengenalan Dan Penatalaksanaan Demensia Alzheimer. Konsensus Nasional AAzI 2002

Penilaian SDG 15
Skor: Hitung jumlah jawaban yang bercetak tebal dan huruf besar
 Setiap

jawaban bercetak tebal dan berhuruf besar mempunyai nilai 1  Skor antara 5-9 menunjukkan kemungkinan besar depresi  Skor 10 atau lebih menunjukkan depresi

Cognitive Progression
Presymptomatic
Neuropsychological

Clinical Dementia Rating

CDR 0.5 CDR 1 CDR 2 CDR 3

MCI

Progression

Functional

Time (years) Adapted from Daffner & Scinto, 2000