Generalized Neurodegenerative dementias AD Dementia with Lewy Bodies (DLB) Mixed Frontotemporal Lobar Degeneration (FTLD) Others

DLB: Clinical Features 1.Cognitive decline 2.Visual hallucinations 3.Parkinsonism 4.Adverse reactions to neuroleptics 6.Falls / syncope / transient loss of consciousness 5.Other psychotic features

DLB: Cognitive Aspects Similar decline rate as in AD, leading to global dementia Fluctuations of attention Deficits of executive function, visuospatial ability and verbal fluency might be more prominent than memory deficits

DLB: Visual Hallucinations Recurrent, commonly involving animated figures that might form part of the patient’s ‘daily routine’ and familiar surroundings Patient has insight Reactions vary, most commonly patients are not threatened by the hallucinations

DLB: Parkinsonism Appears around the same time as the other clinical features Bradykinesia and rigidity are prominent Tremor might be mild Hypophonic speech

DLB: Neuroleptics Sensitivity Severe rigid-akinetic side-effects Neuroleptic malignant syndrome

DLB: Other Psychotic/ Psychiatric Features Other types of hallucinations (auditive/mixed) Delusions Depressive symptoms

DLB Falls: May be secondary to Parkinsonism Syncope/Transient loss of consciousness: Might be related to brainstem and autonomic nervous system involvement

DLB: Prevalence Varies % of demented patients at autopsy

DLB: Differential Diagnosis 1. AD / Vascular / Mixed Dementias 2. Parkinson’s Disease with dementia 3. Parkinson’s plus syndromes

DLB: Management (1) Investigations There is no specific test for the diagnosis of DLB. Clinical history is the best available tool. Rule out reversible / other causes of dementia (standard blood work, imaging) Cognitive test / physical exam Ask patient and family about presence of hallucinations

DLB: Management (2) Treatment Acetylcholinesterase inhibitors (Aricept, Exelon, Reminyl) Dopaminergic drugs Most patients do not require treatment for the hallucinations. If they do, small does of atypical neuroleptics might be used (Risperdal) SSRI’s for depression

Vascular and Mixed Dementias

Source: The “Dementia”Directory. Vascular Dementia. Available at Vascular Dementia (VaD) Accounts for about 20% of cases of dementia Another 20% of cases are a combination of AD and vascular causes Usually affects people between 60 and 75 years old Slightly more common in men

Relationship among AD, VaD and other dementias AD VaD Other Cras, 1998

Vascular dementia Abrupt onset and stepwise progression Might involve small, large or any vessel/s History of stroke/s. Hypertension, diabetes and elevated Homocysteine are strong risk factors. Cognitive abnormalities depending on the areas affected “Sub-cortical” symptoms (slow processing, depression, emotional incontinence, somatic complaints) Hachinski Ischemic Score (HIS) vs ADDTC criteria

Hachinski Ischemic score Abrupt onset2 Stepwise deterioration1 Fluctuating course2 Nocturnal confusion1 Preservation of personality1 Depression1 Somatic complains1 Emotional incontinence1 History of hypertension1 History of stroke2 Associated atherosclerosis1 Focal neurological symptoms2 Focal neurological signs1 Associated atherosclerosis1 Focal neurological symptoms2 Focal neurological signs1

Sub-types of Vascular Dementia Cortical vascular dementia or multi-infract dementia –Large vessel disease –Cardiac embolic events  Subcortical vascular dementia or small vessel dementia –Small vessel disease Strategic infract dementia –Large vessel disease –Cardiac embolic events –Small vessel disease Source: Alzheimer’s Disease and related Disorders Annual Editors: Gauthier S., Cummings JL.

Treatments of Vascular dementia –Prevention of further strokes, consider: Anticoagulation if Atrial Fibrillation ECASA Control of blood pressure Diabetes control Lipids control

Mixed dementia Symptoms of both neurodegenerative and vascular dementia Presence of “microangiopathic” disease, White matter disease Same risk factors as for neurodegenerative and vascular dementia. Imaging: Atrophy, lacunar infarcts and white matter disease

Treatment mixed dementia Acetylcholinesterase inhibitors and Stroke prevention

Focal neurodegenerative dementias: Frontotemporal Lobar Degeneration (FTLD) Focal neurodegenerative diseases, affecting primarily temporal and frontal lobes: 1. Fronto-temporal dementia 2. Primary progressive aphasia 3. Semantic dementia

FTLD - General Features 1. Pre-senile dementias (<65 years of age) 2. SPECT Scan: Anterior (frontotemporal defects) 3. Normal EEG 4. Memory and visuospatial functions are normal until the disease is advanced

FTD: Pathological Types Pick’s disease Non-specific frontal degeneration Frontal degeneration with anterior spinal neuron loss

FTD: Clinical Features (I) Behavioral abnormalities. Inertia, loss of volition, decreased initiative. Social disinhibition, loss of insight. Impulsivity, overactivity. Emotional blunting. Stereotyped and perseverative behavior.

FTD: Clinical Features (II) Mean age of presentation: 53 years Predominantly males High familial aggregation

FTD: Clinical Features (III) Cognitive impairment mostly in areas of executive function (planning, judgement, problem-solving) and attention Memory, visuospatial and calculation might be relatively preserved at the beginning Speech might be either economical leading to mutism, or increased / pressed in disinhibited patients

FTD: Treatment / Management No effective treatment available SSRI’s/Dopaminergic Drugs Neuroleptics Genetic Studies (CH 17)

PPA Gradual and progressive non-fluent aphasia during a period of years leading to dissolution of language function Prominence of phonemic errors

PPA Memory, visuospatial, reasoning, insight, judgement and behaviour remain normal for years IADL’s and ADL’s remain normal for years, and patients can learn new things such as sign language

PPA Difficulties with single word repetition Writing is preserved early in the disease, but is lost later Language comprehension is also lost later in the disease

PPA Management No effective treatment available Learning of alternative communication skills

SD: Core Features Fluent, empty spontaneous speech Loss of meaning of words Semantic paraphasias Prosopagnosia/associative agnosia Preserved single word repetition and ability to read aloud and write to dictation

SD: Supportive Features Press of speech Idiosyncratic word usage Absence of phonemic paraphasias Preserved calculation Behavioural changes - loss of empathy - narrowed interests - abnormal preoccupation with money

SD Memory and visuospatial are preserved Orientation is normal

Other dementias 1. Associated with Parkinson’s disease: Motor symptoms of Parkinson’s disease predates cognitive dysfunction by years. Most commonly appears in advanced Parkinson’s patients. “Sub-cortical” features: prominent mood abnormalities, apraxia, memory might be preserved.

2.Normal Pressure Hydrocephalus (NPH) Isolated cognitive deficits Gait abnormality (apraxic gait) Incontinence Prominent large ventricles with minimal cortical atrophy Surgical treatment

3.Metabolic disease A. Cobalamin (B12), Folate deficiencies Causing or contributing to dementia? 15-30% of seniors have B12 deficiency May cause white matter disease (demyelination) Most patients with dementia and B12 deficiency don’t improve after B12 therapy B.Hypothyroidism May contribute to cognitive deficits in adults Severe cognitive deficits in children

4. Creutzfeldt-Jakob –Spongiform encephalopathies. –Prion disease –Rapidly progressing dementia causing death within weeks or months of onset. –Initial symptoms might be cerebellar with ataxia, dysarthria and coordination defects. –Animal/blood transmission –Diagnosis: brain protein

Treatment of other dementias No available treatment for dementia associated with Parkinson’s disease, Parkinson’s plus syndromes, alcoholic dementia or infectious dementias. Surgical treatment for NPH. Refer to neurosurgery. Possible post-surgical cognitive improvement and stop progression of the disease.

Care of the patients with dementia (I) Inform and teach the family and caregivers about the nature and progression of the disease. Refer to Alzheimer’s society Driving Power of attorney Respite and home care programs. Future plans Genetic testing?

Care of the patient with dementia (II) Maintain high level of activity (exercise programs, daily activities). Nutrition. Check for weight loss and nutritional indices (B12, albumin) Encourage personal and social functions as much as possible

Common problems in patients with dementia (1) 1.DELIRIUM: Defined as fluctuating impairment of attention and orientation, usually of acute onset and due to a medical condition. Reversible 50% of patients with delirium have underlying dementia Presence of delirium precludes cognitive testing for dementia

Common problems in patients with dementia (2) 2.NUTRITION: Most patients with dementia have some degree of malnutrition, which is worse as the disease advances. Use of nutritional supplements and multivitamins is recommended. 3.INCONTINENCE: Usually a late manifestation. Many drugs used for treatment of incontinence will worsen cognition. 4.SLEEP DISTURBANCE: Very common, avoid medications as much as possible.

Other dementias Parkinson’s disease B12 deficiency – Metabolic Normal pressure hydrocephalus Parkinson’s plus syndromes (Multiple systems atrophy or MSA, Progressive supranuclear palsy or PSP) Infectious: Creutzfeldt-Jakob, HIV, Syphilis Alcohol related

Prognosis Poor at present: –Most patients suffer progression of the disease manifested first by increased dependence on caregivers, and latter by loss of capacity to perform basic activities of daily living. –Patients with advanced dementia will suffer incontinence, motor abnormalities and finally death.

Future perspectives Current clinical trials on vaccines: –APP –Promising results on animal experimentation Neuro-regeneration drugs: –Nerve-growth factor Better understanding of environmental and genetic factors that might contribute or trigger the disease. Further development of “symptomatic” drugs