Dementia & Delirium By Olusegun Baiyewu Professor of Psychiatry University of Ibadan.

In the beginning Let not sleep e’er close thy tired eyes without asking thyself: What have I omitted and what have I done? Abstain though if ‘tis evil; preserve if good --Pythagoras

Delirium Diagnostic Criteria Relationship with medical diagnosis Differentiating from dementia Laboratory and Radiological Investigations Treatment Contributions from Alcohol and drugs Rating Scales eg Delirium Index(DI) McGusker et al 1998, Delirium Rating Scale (DRS) Trzepacz et al 1988

What does a psychiatrist need to know Dementia is classified in DSM and ICD as a mental disorder. 1.Dementia involves (a)Cognition (b) Functioning. (c)Behavior

History Over the years – a lot of attention has been given to cognitive aspects. Some to functioning But little to behavior. Original description of Aloz Alzheimer stated that the patient had both memory problems and delusions Martin Roth earlier description gives insight into outcome

HISTORTY II ALOZ ALZHEIMER DESCRIBED A 51 YEAR OLD LADY WITH DELUSIONS,HALLUCINATIONS AND OTHER PSYCHOTIC FEATURES ALONG WITH COGNITIVE IMPARMENT (Alzheimer.A 1907) FROM ANTIQUITY (1785) CAME THE DESCRIPTION OF A MAN WHO HAD DEMENTIA AND DELUSION. THE MAN BELIEVED HE WAS GOING TO BE KILLED AND SAUSAGES WOULD BE MADE FROM HIS FLESH. (Forstl H, Howard R, Burns A, Levy R 1991)

FEATURES IT WAS ESTIMATED THAT $90BILLION WAS SPENT ON ALZHEIMERS DISEASE (AD) IN THE UNITED STATES IN (National Institute of Aging) AD IS THE MOST COMMON TYPE OF DEMENTIA ABOUT 66%.ESTIMATE FROM IBADAN DEMENTIA PROJECT PUTS PERCENTAGE OF AD AT 64% OF ALL DEMENTIAS. OTHER TYPES INCLUDE VASCULAR, FRONTO-TEMPORAL, LEVY BODY. DEMENTIA OCCURS LESS FREQUENTLY IN THE DEVELOPING COUNTRIES OF CHINA, INDIA AND NIGERIA.

WHAT IS DEMENTIA DSM IV DEFINITION: DEMENTIA IS A CHRONIC DISEASE IN WHICH THERE ARE MULTIPLE COGNITIVE DEFICIT OF MEMORY, APHASIA, APRAXIA, AGNOSIA, AND DISTURBANCE OF EXECUTIVE FUNCTIONING LKE PLANNING AND ABSTRACTING. THESE DEFECTS MUST CAUSE SIGNIFICANT IMPAIRMENT OF OCCUPATIONAL AND SOCIAL FUCTIONING, AND MUST NOT BE DUE TO NERVOUS SYSTEM ILLNESS, SYSTEMIC ILLNESS, SUBSTANCE USE DISORDER,OR A PSYCHIATRIC CONDITION, AND MUST NOT BE IN THE PRESENCE OF A DELIRIUM.

Pathology As been reported in histology 1.Amyloid plaques 2.Neurofibrilary tangles 3.Cortical Atrophy.

Biochemistry etc Amyloid Precausor Proteins Homocystein, oxidative stress ApoE- cholesterol Hipocampal volume changes-Ethorhinal cortex

COMPONENTS DEMENTIA HAS THREE COMPONENTS. COGNITIVE FUNCTIONAL BEHAVIORAL BEHAVIORAL COMPONENT HAS BEEN NAMED BEHAVIORAL AND PSYCHOLOGICAL SYMPTOMS IN DEMENTIA (BPSD)

Types Distinguish between treatable and non-treatable forms of dementia By 1.History 2.Mental State Examination 3.Laboratory and Radiological evaluation

Clinical Types Alzheimer’s Disease % Vascular Dementia % Lewy Body Dementia (McKieth) c 15% Fronto-temporal Dementia Others

Clinical Evaluation Diagnosis- largely clinical Should be supported by Lab and radiology Can be supported by neuropsychological test MMSE,Blessed Consortium to Establish a Registry for Alzheimer’s disease

Results Some prevalent studies comparing developed and developing countries report lower rates in developing countries Others report rates similar to those of western societies Incidence rates are more reliable and two studies from developing countries report lower rates (Hendrie et al, Chandra et al) There are fewer incidence studies because it has to be longitudinal and are expensive

PREVALENCE DEMENTIA IBADAN DEMENTIA 2.29% AD 1.41% INDIANAPOLIS DEMENTIA 4.82% AD 3.69% (Community) Community & DEMENTIA 8.24 % AD 6.24% Nursing Home Li et al 1989, in Beijing, China, and Chandra in India had such low prevalence rates

Some Other Prevalence Studies DementiaAD China (Li et al 1989) low low (Zhang et al 1990) not low not low Korea (Lee et al 2002)8.2%5.4% Sri Lauka (De Silva et al 2003)3.98%(71% of total dementia were AD)

Incidence Rates SitesDementiaAD Indianapolis-Ibadan (Hendrie et al 2001) Indianapolis3.24% 2.52% Ibadan1.35% 1.13% Indi-US study (Chandra et al 2001) Ballabgarh (India)n/a 4.7 per 1000 person years Monongahela (USA)n/a 17.5 per 1000 person years

Risk for migration 1. A number of studies have compared population that migrated to those at place of origin 2. Some have compared two dissimilar population living in different places 3. Some have compared different groups in the same neighborhood 4. Differences were found either in rates or risk factors.

Epidemiology 1. Most studies in the western societies have recorded prevalence rates of between 5-10%. 2. There is increasing prevalence with age. 3. ApoeE4 and cardiovascular factors are some of the important risk factors. 4. Higher incidence of death and/ or decline when compared with age matched normal controls.

Risk Factors Common risk factors include ApoE 4 –different reports on its relationship to AD Vascular risk factors- important in AD, Vascular and Mixed Dementias Age Gender Others What risk factors influence survival?

Nueropsychlogical tests Most neuropsychological test materials are developed for middle class white societies in Europe and North America Their application outside this group usually leads to some difficulties and modifications will be needed

Appropriate modifications Researchers in these societies must develop questionnaires,that consider local environment while retaining the concept – An example is the Community Screening Interview for Dementia (Hall et al 2001). This is currently in use in studies in many developing countries (Prince et al.2003)

Validity The Mini Mental Sate Examination (MMSE) is one of the most frequently used screening instruments In studies done in western societies, a score of 24 or below raises suspicion of dementia or delirium.However subjects in non-western societies may have difficulties with aspects of the MMSE like draw an interlocking polygon,or write a sentence.

The stick design I grow old ever learning many things.- Solon.

Functioning Some items that measure functioning might not be applicable in some culture eg driving a car, filling tax forms and writing checks. Even more simple tasks like cooking and shopping might be taken off the elderly in the multi-generational family setting found in some developing countries. Responses to these questions are crucial in deciding between MCI and early AD

Behavior Symptoms Reports from various countries observe different symptoms and different levels of severity. Severity and distress to caregivers influence institutionalization and probably survival. Are there behavior symptoms that could become part of criteria for diagnosis?

BPSD BPSD CONSISTS OF THE FOLLOWING DELUSION HALLUCINATION APATHY PERSONALITY CHANGE DEPRESSION ELATION ANXIETY AGITATION/ WANDERING NIGHTTIME DISTURBANCE APPETITE CHANGE.

BPSD CONTD BPSD IS THE MOST IMPORTANT RISK FACTOR IN NURSING HOME PLACEMENT Balestreri et al 200 IT IS AN IMPORTANT CAUSE OF CAREGIVERS BURDEN (Cummings & Victoroff 1990, Merrian et al 1988, Reisberg et al 1987). IT IS ASSOCIATED WITH MORTALITY IN ALZHEIMER’S DISEASE Gilley 2000

DEMENTIA FOLLOW UP 40 OF THE 90 SUBJECTS EVER DIAGNOSED DEMENTIA WERE SEEN IN SUBJECTS WERE ADMINISTERED MMSE CAREGIVERS WERE ADMINISTERED NEUROPSYCHIATRIC INVENTORY AND BLESSED DEMENTIA SCALE.

RESULT MEAN AGE OF SUBJECTS WAS 84.7 (10.3) YEARS MEAN AGE OF CAREGIVERS WAS 42.0 (16.4) YEARS 10 CAREGIVERS WERE MALES,30 WERE FEMALES-USUALLY DAUGHTERS APPETITE CHANGE WAS THE MOST COMMON SYMPTOM,FOLLOWED BY DEPRESSION AND IRRITABILITY. NPI SCORES BECAME WORSE WITH DECLINING SCORES ON MMSE THE MORE DISTRESSFUL SYMPTOMS TO CAREGIVERS WERE DEPRESSION, IRRITABILITY,NIGTHTIME BEHAVIOUR AND DISINHIBITION

FACTORS ASSOCIATED WITH CAREGIVERS BURDEN SCREAMING PHYSICAL AGGRESSION PERSONALITY CLASHES WANDERING DEPRESSION RESISISTANCE TO HELP WITH ADL (dressing, washing,eating toileting SUSPICIOUSNESS NOT SLEEPING AT NIGHT

BIOLOGICAL MARKERS NEUROIMAGING AGITATION AND DISINHIBITON ARE ASSOCIATED WITH METABOLISM IN FRONTAL AND TEMPORAL LOBES PSYCHOSIS IS ASSOCIATED WITH METABOLISM IN FRONTAL LOBE ANXIETY/DEPRESSION IS ASSOCIATED WITH METABOLISM IN PARIETAL LOBE (Sultzer 1996) AD PATIENTS WITH DELUSION HAVE. LOWER PERFUSION IN THE SUPERIOR AND INFERIOR TEMPORAL CORTEX (Starkstein et al 1995)

BIOLOGICAL MARKERS IN BPSD PATHOLOGY AD PATIENTS WITH PSYCHOTIC SYMPTOMS HAD LOWER NEURONAL COUNT IN 1. PARAHIPPCAMPAL GYRUS, 2.REGION CA1 OF THE HIPPOCAMPUS, 3.DORSAL RAPHE, 4.LOCUS CORELUS- Forstil et al DELUSIONS AND HALLUCINATIONS HAVE BEEN FOUND TO BE RELATED TO HIGHER SENILE PLAQUES IN THE PRESUBICULUM HIGHER TANGLE COUNT IN THE FRONTAL CORTEX INCREASED DENSITY OF EXTRACELLULAR TANGLES IN THE PARIETAL LOBE HIGHER NUMBER OF NEURITIC PLAQUES IN THE OCCIPITAL CORTEX Zubenko et al 1991,Mkaetova-Ladinska et al 1995

TREATMENT PHARMACOLOGICAL AND NON PHARMACOLOGICAL NON-PHARMACOLOGICAL INCLUDE RECREATIONAL,PSYCHOLOGICAL INTERVENTIONS, ENVIRONMENTAL MANIPULATIONS, MUSIC THERAPY AND PSYCHOEDUCATION FOR CAREGIVERS PHARMACOLOGICAL TREATMENT COGNITIVE IMPAIRMENT BY VITAMIN E AND OTHER ANTI-OXIDANTS CHOLINE-ESTERASE INHIBITORS DONEPEZIL (ARICEPT) RIVASTIGMINE (EXCELLON) GALANTAMINE

New goals in treatment Anti –Amyloid therapy Vaccination Anti histamine- Dimebon Others

TREATMENT CONTD TREATMENT OF BEHAVIOR SYMPTOMS SERTONINE SPECIFIC RE-UPTAKE INHIBITORS ATYPICAL ANTIPSYCHOTICS- OLANZEPIENE,RISPERIDONE,CLOZAPINE, QUETIAPINE ANTI-CONVULSANTS CARBAMAZEPINE SODIUM VALPORATE.

TREATMENT CONTD THERE ARE CONTROVERSIES ON THE USE OF THE ATYPICAL NEUROLEPTICS IN TREATING PSYCHOTIC SYMPTOMS IN DEMENTIA THIS HAS BEEN LINKED TO ADVERSE CEREBROVASCULAR RELATED EVENTS. SOME REGULATORY AGENCIES ADVISE CAUTION IN THEIR USE. NO NEUROLECTIC HAS BEEN APPROVED SPECIFICALLY TO TREAT PSYCHOTIC SYMPTOMS IN DEMENTIA

PSYCHIATRIC DISORDERS 23 OUT OF 29 RESIDENTS OF TWO NURSING (OLD PEOPLES) HOMES IN LAGOS WERE STUDIED. 74% OF THEM HAD PSYCHIATRIC DISORDERS 11(48%) HAD DEMENTIA 4(17%) HAD DEPRESSION, 1 HAD SCHIZOPHRENIA 6 (26%) HAD NO PSYCHIATRIC DISORDERS MEAN AGE WAS78.74(8.55) YEARS 12 MALES, 11 FEMALES Baiyewu O, Adeyemi JD, Ogunniyi A Int J Geriat Psych(1977) 12: NURSING HOME STUDY

What should be goal for the future? 1. AD -has received more attention in research than other dementias. 2. There is need for more studies on Vascular, Lewy Body, and Fronto-temporal dementias 3. An increased need to correlate clinical findings with post mortem findings.

Goals for the future contd. What tests – Biochemical, Neuropsychological Radiological could be useful in future? A lot of interest is now shown in the pre-dementia stage MCI or even in subjects with subjective memory complaints.