1. The Malfunctioning Mind: Degenerative Diseases of the Brain
Andrea Mejia.
Spring 2017

2. Defining: Normal aging
Declining abilities
Cognitive processing speed
Fluid intelligence
Divided attention
Learning efficiency
Source memory
Visuoperceptual functioning
Stable (improved?) abilities
Crystallized intelligence = learned knowledge and experiences
Age related cognitive decline (ARCD) –ARCD is used interchangeable with “normal aging”. Those with ARCD are coined as the “worried well”. Applies to the clinical situation where an older person is worried about their memory – to the degree they complain to their PCP therefore prompting a referral – but there is no objective evidence of memory impairment.

3. Defining: Dementia Loss of intellectual capacity and/or personality
Due to loss and/or damage of neurons
Reversible
Infection, autoimmune, toxic, metabolic
Nonreversible
Static: stroke, Korsakoff’s, head injury
Degenerative: Alzheimer's, Lewy Bodies, vascular, frontotemporal

4. Degenerative Dementia
Intrinsic to the nervous system and affect certain neural systems selectively
Presumed to have a degree of genetic transmission
Alzheimer’s, Parkinson’s, frontotemporal dementia, etc.

5. Nondegenerative Dementia
Diverse etiologies, including vascular, endocrine, inflammatory, nutritional deficiency, and toxic conditions
Infectious dementia (AIDS dementia), demyelinating dementia (multiple sclerosis), chronic alcohol or drug abuse (Korsakoff’s syndrome), etc.

6. Alzheimer’s Disease: Diagnostic Criteria and Associated Features
Gradual onset
Worsening of cognition
One of two categories must be present
Amnestic presentation – most common
E.g. learning impairment and of recall of recently learned information
Nonamnestic presentations
Language, most common word-finding
Visual, most common spatial cognition
Executive dysfunction, most common reasoning, judgment, problem solving
Onset of months to years, not sudden over hours or days
Worsening of condition by report of observation
Visual – also object agnosia, impaired face recognition

7. Alzheimer’s Disease: Epidemiology
Most common dementia
Increasing prevalence
Higher prevalence
With age
Developing nations
Women
African Americans, Hispanics
Survival
2-20 years from diagnosis
1/3 seniors dies with Alzheimer or other dementia
2/3 of americans with Alzheimer’s disease are women
In the U.S. someone develops Alzheimer’s ever 66 seconds

8. Alzheimer’s Disease: Genetic Factors
Family history = risk factor
Esp. with early onset
Three identified genes…still many ?s
Having a gene doesn’t mean you will acquire Alzheimer’s...or vice versa
But there are three genes that will cause someone to invariably develop AD
Down syndrome
Neuropathological changes consistent with AD
By age 40 in most
- For the 3 genes – all 3 causative gene mutations are associated with an early age of onset (occurring before the age of of 65)

9. Alzheimer’s Disease: Neuropathology
Neuronal loss with cortical neuronal shrinkage
Correlates with dementia severity
Generalized cortical atrophy
Sulcal widening, gyral atrophy
Increased ventricular size
Neurodegenerative changes begin in the medial temporal lobe
Spread to frontal, temporal, and parietal lobes

11. Alzheimer’s Disease: Neurocognitive Profile
Memory
Episodic memory impairment
Begins with recent memories
Language
Word-finding difficulties
Grammar and syntax less and less complex
Visuospatial functioning
Disorientation in familiar places
Object misplacement

12. Alzheimer’s Disease: Neurocognitive Profile
In later stages:
Executive dysfunction
Planning, sequencing, abstracting
Agnosia
Recognizing objects
Apraxia
Learned motor acts

13. Alzheimer’s Disease: Other symptoms
Depression
Apathy and agitation
Anxiety and delusions (often paranoid)
Later stages
Visual hallucinations
Very advanced stages

14. Neuropsychological Testing of Alzheimer’s Patients
Digit Symbol
Block design
Clock drawing
Object naming
Memory
Deficits on tests of both left and right hemisphere function
Maybe demonstrate if you would like

15. Alzheimer’s Disease: Neuroimaging
Structural neuroimaging (MRI, CT)
Cortical atrophy
Esp. temporal structures (e.g., Hippocampus)
Problem: Overlap with other dementias, normal aging

16. Alzheimer’s Disease: Neuroimaging
Functional neuroimaging (fMRI, PET, SPECT)
Reduced activation of multiple regions
Temporal
Parietal

17. Alzheimer’s Disease: Treatment
Other treatment strategies besides medications
Manage depression, anxiety, sleep, psychosis
Basic schedules, notebooks, calendars
Mixed rehabilitation showed improvement in individuals with MCI, but not early AD
Caregiver education and support
MCI – stage before getting dementia and after normal aging
- speaks to importance of early, or preclinical diagnosis.

18. Dementia with Lewy Bodies: Diagnostic Criteria
Central feature
Progressive dementia interfering with social or occupational function
Memory impairment
Deficits on tests of attention, executive function, and visuospatial
Core features
Fluctuating attention, visual hallucinations, parkinsonism
Depression
Additional features
REM sleep-behavior disorder, depression, delusions, autonomic dysfunction (hypotension, urinary incontinence), repeated falls and syncope
Memory impairment may not occur in early stages, but is evident with progression
Deficits on tests of attention, executive function, and Visuospatial ability may be especially prominent
Spontaneous features of parkinsonism
Additional features – some are “suggestive” meaning, 1 or more must be present in the presence of one or more core features, a diagnosis of probable DLB can be made. Some are “supportive” features, meaning commonly present but not proven to have diagnostic specificity

19. Dementia with Lewy Bodies: Epidemiology
Found in about 20-35% of elderly with dementia
Second most common cause of neurodegenerative dementia
Prevalence does not increase with advancing age
2nd, following AD
Unlike AD, prevalence does not increase with age...
MORE COMMON IN MEN
Clinical presentation is often striking not only for the parkinsonism, but also for dramatic fluctuations in patients’ level of arousal, the vivid hallucinations and the histories of dream enactment behavior during sleep

20. Dementia with Lewy Bodies: Neuropathology
Cortical DLB
Limbic (e.g. amygdala) and temporal regions, with lesser involvement of frontal and posterior cortical regions
Subcortical DLB
Hypothalamus, basal forebrain, midbrain Tegmentum
Overlap with AD
AD pathology at autopsy common
Other brain regions for subcortical DLB -
Overlap with AD
Dementias of DLB and AD are similar in onset and progressive course
Prior to autopsy many patients with Lewy body diesease had been given the diagnosis of AD

21. Dementia with Lewy Bodies: Genetics
No genes have been identified for DLB

22. Dementia with Lewy Bodies: Neuropsychological Profile
Compared to AD, DLB patients have greater deficits in attention, letter fluency, visual perceptual organization, and visual constructional skills
Significant visual spatial deficits
Mild memory difficulties (in comparison to AD)
- Prominent clinical presentation involves deficits in attention and concentration and problems in complex visual perceptual processing

23. Dementia with Lewy Bodies: Treatment
Cholinesterase inhibitors
More severe deficits than in AD patients
Attention, psychiatric, hallucinations
Many will show remarkable improvement
Dopaminergic agents
Levodopa  motor function, alertness
Typically responsive, but some adverse reactions
AVOID ANTIPSYCHOTICS
Severe reactions
Risk displaying neuroleptic malignant syndrome
*Cholinesterase – profound cholinergic neuronal loss and severe depletion occurs early in DLB, unlike AD until late stages. Neuronal loss and depletion affects attention, and visual disturbances, and does not impair memory
Therefore cholinesterase inhibitors are more successful with DLB then AD
Thus cholinergic depletion is a critical factor in the symptom manifestation of early DLB but appears to be less so in AD
This finding highlights the importance of differentiating btw early versus late stages of different dementias since patients with advance AD may have similar clinical features to those with early DLB*
**** may be too specific but shows they are different or treated different although there are many similarities with AD and DLB