Basic Behavioral Neurology Clinical Concepts

Mild cognitive impairment

Definition

- Alzheimer Disease Research Center (ADRC) criteria (Albert et al, 2011)

1. Concern regarding an intraindividual change in cognition
2. Impairment in one or more cognitive domains
3. Preservation of independence in functional abilities
4. Not demented

- Petersen criteria (Petersen 2016)

1. Memory complaints per subject and/or collateral source
2. Intact activities of daily living
3. Clinical dementia rating scale of 0.5
4. Performance on a delayed memory test that is at least one standard deviation below the mean for the subject’s age

- Epidemiology (Petersen 2016)

1. 15-20% of patients over the age of 60 have MCI
2. Not everybody with MCI will progress to develop dementia
3. The annual rate in which MCI progresses to dementia varies between 8% and 15% per year

Levels of Functioning (Salardini 2019)

• Activities of daily living: dressing, bathing, toileting, continence, transferring, eating
• Instrumental activities of daily living: shopping, preparing food, housework, laundry, use transportation, medication compliance, handling finances
• Advanced activities of daily living: vocational skills, vocational knowledge, hobby-related mastery, music, art

Dementia

Definition (McKhann 2011)

Cognitive or behavioral (neuropsychiatric) symptoms that:

1. Interfere with the ability to function at work or at usual activities; and
2. Represent a decline from previous levels of functioning and performing; and
3. Are not explained by delirium or major psychiatric disorder.
4. Cognitive impairment is detected and diagnosed through a combination of
   1. History-taking from the patient and a knowledgeable informant and
   2. Objective cognitive assessment, either a “bedside” mental status examination or neuropsychological testing
5. The cognitive or behavioral impairment involves a minimum of two of the following domains:
   1. Impaired ability to acquire and remember new information
   2. Impaired reasoning and handling of complex tasks, poor judgment
   3. Impaired visuospatial abilities
   4. Impaired language functions
   5. Changes in personality, behavior, or comportment

Epidemiology: 70-80% of dementia is contributable to Alzheimer’s pathology, vascular disease, or some combination of the two; Lewy body disease contributes to 5%; the rest includes a large number of pathologies with lower prevalence (McKhann 2011)

Basic Overview of Dementias

(McKhann 2011)

Alzheimer dementia

• presenting cognitive syndrome: amnestic, logopenic variant, posterior cortical atrophy, dysexecutive AD
• risk factors: age, vascular risk factors, TBI, low education, genetics
• characteristic lesions: amyloid plaque (Abeta42), fibrillary tangles (P-tau)

Vascular dementia and subcortical ischemic vascular disease

• presenting cognitive syndrome: large vessel is highly variable; small vessel presents with subcortical cognitive impairment
• risk factors: age, vascular risk factors (HTN, DM, HLD, smoking, etc.), genetics
• characteristic lesions: white matter hyperintensities, microhemorrhages, lacunes, enlarged perivascular spaces

Frontotemporal dementia

• presenting cognitive syndrome: language variant - Nonfluent / agrammatic variant primary progressive aphasia (mostly tau), Semantic variant primary progressive aphasia (mostly TDP), lvPPA (AD > FTLD); Behavioral variant frontotemporal dementia - TDP or tau
• risk factors: environmental factors, genetics
• characteristic lesions: Tau (Pick’s disease, FTDP-17), TDP-43 (various types including ALS-FTLD), FUS

Parkinson's disease dementia

• presenting cognitive syndrome: subcortical dementia
• risk factors: TBI, family history of PD, environmental pesticides
• characteristic lesions: alpha-synuclein predominantly in subcortical structures

Dementia with Lewy bodies

• presenting cognitive syndrome: hallucinations, fluctuation in cognition and level of alertness, Parkinsonism, visuospatial problems, dream enactment (due to REM-sleep behavior disorder)
• risk factors: family history of PD, susceptibility genes (APOE4), low education, vascular risk factors, depression and anxiety. Protective: smoking, history of cancer
• characteristic lesions: alpha-synuclein predominantly in cortical area, high degree of coexistence of amyloid pathology

Progressive supranuclear palsy (Steele-Richardson-Olszewski)

• presenting cognitive syndrome: slow vertical saccade, gait instability, Parkinsonism (poorly-responsive to levodopa)
• risk factors: not well understood
• characteristic lesions: tufted astrocytes, tau and neurodegeneration in brainstem and basal ganglia

Corticobasal syndrome / corticobasal degeneration

• presenting cognitive syndrome: asymmetrical apraxia, asymmetrical dystonia or myoclonus, and Parkinsonism, some patients exhibit alien-limb phenomenon
• risk factors: not well understood
• characteristic lesions: achromatic ballooned neurons, 4R tau mostly, astrocytic plaques, parietal and temporal (perisylvian) atrophy

References

Albert, M. S. et al. The diagnosis of mild cognitive impairment due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 270–279 (2011) PubMed link

McKhann, G. M. et al. The diagnosis of dementia due to Alzheimer’s disease: Recommendations from the National Institute on Aging-Alzheimer’s Association workgroups on diagnostic guidelines for Alzheimer’s disease. Alzheimers Dement. 7, 263–269 (2011). PubMed link

Petersen, R. C. Mild Cognitive Impairment. Continuum 22, 404–18 (2016) PubMed link

Salardini, A. An Overview of Primary Dementias as Clinicopathological Entities. Semin. Neurol. 39, 153–166 (2019). PubMed link