16.1. Introduction
General Considerations of Dementing Illnesses
Most dementing illnesses have specific clinical patterns of deterioration, destroy particular areas of the brain in a sequential manner and are associated with seminal features. They are now being categorized on a molecular biological, genetic and neuropathological basis.
As noted in the beginning of the chapter on behavioral neurology, the brain appears to function normally as an incredibly complicated assembly of integrated loops. There clearly is long term potentiation and long term depression in many aspects of learning and memory. In the former, specific integrated loops and neurons have greater synaptic efficiency whereas in the latter these neurons are suppressed and their synapses cannot fire. Neurotransmitter systems such as acetylcholine have been associated with memory and many other aspects of cortical function. The interplay of GABAergic and acetyl cholinergic systems at the thalamic level appears to be important in the state of consciousness and directed attention. Dopamine has a major role in basal ganglia function at all levels and most probably with subcortical dementia. Serotonin has been shown to be pivotal in many aspects of emotional expression and pain. Thus, dementing processes that destroy neurotransmitter systems in the brainstem may have far reaching neurological manifestations.
A fundamental aspect of all dementing processes appears to be the loss of synapses as well as neurons. Synaptic loss is the best correlate of the severity of dementia. Synaptogenesis and maintenance of formed synapses may depend on functional use, neurotrophic factors and connectivity. Synaptic "pruning" certainly occurs in many of the childhood and early adult storage diseases.
The intense interest in the formation of nuclear and cytoplasmic inclusions points to the role of protein metabolism in cell function. The exact mechanism of cellular death when inclusions are found is not known, but is suspected to be failure of normal axonal transport, apoptosis or inability to control free radicals. Synucleopathies, in which alpha-synuclein is a major component of nuclear inclusions, are often clinically associated with hallucinations. The tauopathies are characterized by hyperphosphorylation of tau protein in neurons and glia.
The electrical correlates of normal brain function and that which occurs with dementing illness is now being unraveled. The EEG is often slow in dementing illness. The ability to make cortical negative variants or readiness potentials prior to a movement or specific task allows some insight into the brain's functional activity. The recent discovery of thalamically generated gamma waves points to their importance in perception. Magnetoencephalography allows for a precise localization of an electrical event that is time locked. Its major use at the moment is to help localize epileptic foci. It appears to take 0.5 msec to process a stimulus to a perception. This figure has come from an analysis of cortical negative variant potentials and thalamically generated gamma waves.
Functional MRI, PET and SPECT all localize an area of activity during a specific event, but do not detail the sign of the event (inhibitory or excitatory) or localize its precise origin, the synapse or neuron. Most (estimated to be 85%) of electrical activity occurs at synapses. Further complicating this particular aspect of neural function is the precise anatomy of the synaptic connection. Whether it is on the pedicle of the spine or the neuron itself may determine the functional activity of this neuron (excitatory or inhibitory).
The clinical entities detailed below probably will not be subject to change. Their underlying mechanisms will be discovered and then they will show the dynamic plasticity of the nervous system and will move into different categories.
Clinical features of Dementing Illnesses
- Fundamental characteristics of a dementing illness:
- The cognitive impairments is acquired
- The impairment involves multiple domains of cognitive function
- There is no impairment of arousal
- Deterioration of previously acquired intellectual abilities of sufficient severity to interfere with social or occupational function
- Memory impairment with at least one other aspect of cognitive behavior
- Disturbances of higher cognitive function:
- Personality change
- No intoxication or delirium
Basic Clinical Features of Cortical Dementias
- Neuropsychological deficits:
- Memory impairment:
- Recall not aided by cues
- Decreased retention
- Dysphasia
- Dyspraxia
- Agnosia
- Poor visuospatial abilities
- Decreased problem solving
- Speed of cognitive function:
- Psychiatric manifestations:
- Depression
- Hallucinations
- Day to day variability (LBD)
- Delusions
- Apathy
- Motor abnormalities:
- Depends on specific dementing illness; often specific (loss of vertical gaze PSP; asymmetry, corticobasal ganglionic degeneration)
- Severity and progression:
- Dependent on specific dementing illness
- Significant inter and intrafamilial variance in genetic illnesses
- Variability is the rule in sporadic disease
Basic Clinical Features of Subcortical Dementia
- Neuropsychological deficits:
- Frontal memory impairment:
- Recall aided by cues
- Decreased verbal fluency and recall
- Speed of cognitive function:
- Psychiatric manifestations:
- Motor abnormalities:
- Dysarthria
- Extrapyramidal signs
- Severity and progression:
- Mild to moderate
- May be intermittent due to specific structural lesions
Primary Dementing Illnesses
Definition of Primary Dementing Illnesses
- Primary characteristics of dementia will be a feature of the clinical presentation of the illness.
- Differential diagnosis of primary degenerative dementing disease:
- Alzheimer's disease
- Dementia with Lewy bodies (DLB)
- Frontotemporal dementia and variants
- Multiple system atrophy:
- Striatonigral degeneration (SND)
- Olivopontocerebellar atrophy (OPCA)
- Shy–Drager syndrome (SDS)
- Corticobasal ganglionic degeneration (CBGD)
- Progressive supranuclear palsy
- Hallervorden–Spatz disease
- Creutzfeldt–Jacob disease
- Gerstmann–Straüssler–Schenker
- Wilson's disease
- ALS with dementia
- Huntington's disease
- Pick's disease
- Primary progressive aphasia (late stages)
- Heidenhain variant of JC disease
- Posterior dementia with medial temporal sclerosis
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