Introduction to Degenerative Dementing Diseases Diagnosis & Management Issues. Marilee Monnot, Ph.D., Assistant Professor Department of Neurology, College of Medicine OU Physicians CENTER for MEMORY LOSS and DEMENTIA University of Oklahoma Health Sciences Center

Dementia: A Description of Behavior Dementia means a progressive decline in cognitive and behavioral competence, compared to former abilities. Many diseases can cause dementia. Degenerative dementia is a permanent, incurable state caused by diseases that kill brain cells progressively. Each disease usually starts in a different part of the brain, causing different initial symptoms.

Basic Diagnostic Criteria for Degenerative Dementing Diseases Insidious progression Not due to another medical disorder or delirium Multiple cognitive deficits (2 or more)  Memory (short and/or long term)  Language (aphasia, anomia, etc.)  Judgment & planning (executive functions)  Motor functions (apraxia, etc.)  Perceptual problems (agnosia, etc.)  Abstracting difficulties (analogies, pattern recognition, etc.)

Dementia Disease Classification Cortical dementias  Alzheimer’s (familial and non-familial)  Frontotemporal & temporopariental Sub-cortical dementias  Corticobasal ganglionic degeneration  Huntington’s and Parkinson’s  Progressive supernuclear palsy Mixed cortical and subcortical dementias  Vascular dementia (many small strokes)  CJD – “mad cow” disease  Alcoholic dementia  AIDS dementia

Alzheimer’s Disease (AD) Most common and well-known of the degenerative dementing diseases (1% at 65 yrs, but 50% at 85 yrs of age). Starts in the entorhinal cortex, & visual processing areas of the cortex (↓cholinergic function). Destroys ability to lay down new memories (caregivers can’t correct, argue with, or remind patients), but remote memories are preserved. Patients usually have adequate social skills until later stages of illness, when perceptual & judgment abilities are greatly impaired. Progresses (last to go is the motor strip)

MRI scan of healthy (left) and AD (right) brains showing entorhinal cortex atrophy:

Dementia with Lewy Bodies (LBD) 3 variants (pathology: Lewy Body variant of AD, dementia associated with Parkinson’s disease, & Lewy Body pathology without Parkinson’s) Prevalence: 1/3 the number of AD patients Starts at earlier ages Predominance of males Clinical syndrome:  Persistent visual hallucinations  Marked fluctuation of cognitive functions  Fluctuating Parkinsonism with sensitivity to neuroleptics and unresponsiveness to Parkinson medications

Fronto-Temporal Dementias (FTD) FTD clinical syndrome (executive dysfunction, apathy, social misconduct, & disinhibition) - 3 main types: 1. Pick’s disease – only one hemisphere affected 2. Primary Progressive Aphasia – left hemisphere degeneration in right-handed patients (aphasia, anomia) 3. Semantic Dementia – left temporal lobe disease causes fluent dysphasia (severe difficulty in naming & word meaning comprehension), & associative agnosia (loss of procedural knowledge)

FTD (continued) -Right degeneration results in disinhibition. -Left degeneration results in withdrawal. -Bilateral degeneration: echolalia, echopraxia (inappropriate copying behaviors) linguistic problems (anomia) mutism, apathy, amotivational states affective mood syndromes psychotic symptoms (delusions, paranoia, etc.)  memory, but not as severe as in AD (poor recent and remote memory)

FTD (continued) Neuropsychological testing results:  semantic paraphasias (saying ‘spoon’ for fork)   confrontation naming (identifying objects/pictures)   word definition   recognition of visually-presented objects   poorer phonemic naming vs category naming Phonemic = words beginning with letter ‘c’ or ‘m’ Categorical = name animals, or fruits/vegetables, etc.

Subcortical Dementias Cortiobasal ganglionic degeneration  Unilateral rigidity and gait problems  Apraxia (inability to use objects properly, or perform deliberate movements)  Alien hand syndrome (movements without conscious intent) and tremor  Reflex myoclonus (muscle spasms or twitches)  Cortical sensory loss (poor temperature perception, etc.)  Chorea (writhing limbs & facial muscles), and/or choreoathetosis (chronic tight muscles, lack of muscle tension, proximal jerky involuntary movements, etc.)

Subcortical dementias (cont.) Huntington’s Disease - traced to emigrants (1630) from East Anglican village of Bures, England : Dominant inheritance (1 parent with gene) - CAG Choreoathetosis starting at yrs. of age Dementia & emotional lability also Parkinson’s Disease – substantia nigra & dopamine loss  Bradykinesia (slowness of movement)  Resting tremor, rigidity, postural instability  ↓ facial expression, eye blink rate, arm swing  Dementia occurs very late in the disease

Subcortical dementias (cont.) Progressive supranuclear palsy – tauopathy results in a triad of opthalmoplegia (eye muscle weakness), axial dystonia ( contractions ), & pseudobulbar palsy ( paralysis ) :  Balance problems & falls  Visual disturbances  Slurred speech  Dysphagia (difficulty in swallowing)  Personality changes  Starts with downward gaze problems

Mixed Dementias Vascular Dementia (more emotional lability & depression)  Binswanger’s (many small-vessel strokes)  Multi-infarct (abrupt and/or step-wise progression) Creutzfeldt-Jakob Disease (CJD) = prion disease  ‘mad cow’ acquired variant (15%) & sporadic (85%) Wernicke-Korsakoff syndrome (nutritional, acute onset) Alcoholic dementia  Cerebellar and corpus callosum atrophy  Affective prosody comprehension decline  Gait problems  Abstract reasoning decline more than education knowledge Neurosyphilis & herpes simplex viral infections

Mixed Dementias (cont.) HIV-1 associated dementia (HAD)  1 yr. after AIDS diagnosis = 7% are demented  Acute, abrupt onset during secondary infection  Mood changes & apathy (cortex atrophy)  Distractibility, poor concentration, & forgetfulness  Clumsiness, leg weakness, & balance problems  Hyper-reflexia & sustention tremor  ↓ fine motor tasks

General Behavioral Considerations Demented patients have altered perceptions and judgment, due to the shrinkage of the brain. They do the best they can with a very injured brain. They get upset & scared when they are confused. Speak slowly, in short phrases, with a calm lowered voice tone; wait for them to understand. Have a familiar family member in the treatment room, where the patient can see them during medical or dental procedures. This helps to reassure them and prevent agitation and aggression.