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Alzheimer's disease

A Mind Odyssey

  • Adapted from The ICD-10 Classification of Mental and Behavioural Disorders
    World Health Organization, Geneva, 1992

    F00 Dementia In Alzheimer's Disease

  • Alzheimer's disease is a primary degenerative cerebral disease of unknown aetiology, with characteristic neuropathological and neurochemical features. It is usually insidious in onset and develops slowly but steadily over a period of years.

  • This period can be as short as 2 or 3 years, but can occasionally be considerably longer. The onset can be in middle adult life or even earlier (Alzheimer's disease of presenile onset), but the incidence is higher in later life (Alzheimer's disease of senile onset). In cases with onset before the age of 65-70, there is the likelihood of a family history of a similar dementia, a more rapid course, and prominence of features of temporal and parietal lobe damage, including dysphasia or dyspraxia. In cases with a later onset, the course tends to be slower and to be characterized by more general impairment of higher cortical functions. Patients with Down's syndrome are at high risk of developing Alzheimer's disease.

  • There are characteristic changes in the brain: a marked reduction in the population of neurons, particularly in the hippocampus, substantia innominata, locus ceruleus, and temporoparietal and frontal cortex; appearance of neurofibrillary tangles made of paired helical filaments; neuritic (argentophil) plaques, which consist largely of amyloid and show a definite progression in their development (although plaques without amyloid are also known to exist); and granulovacuolar bodies.

  • Neurochemical changes have also been found, including a marked reduction in the enzyme choline acetyltransferase, in acetylcholine itself, and in other neurotransmitters and neuromodulators.

  • As originally described, the clinical features are accompanied by the above brain changes. However, it now appears that the two do not always progress in parallel: one may be indisputably present with only minimal evidence of the other. Nevertheless, the clinical features of Alzheimer's disease are such that it is often possible to make a presumptive diagnosis on clinical grounds alone.

    Dementia in Alzheimer's disease is at present irreversible.

    Diagnostic Guidelines

    The following features are essential for a definite diagnosis:

    1. Presence of a dementia as described above.
    2. Insidious onset with slow deterioration. While the onset usually seems difficult to pinpoint in time, realization by others that the defects exist may come suddenly. An apparent plateau may occur in the progression.
    3. Absence of clinical evidence, or findings from special investigations, to suggest that the mental state may be due to other systemic or brain disease which can induce a dementia (e.g. hypothyroidism, hypercalcaemia, vitamin B12 deficiency, niacin deficiency, neurosyphilis, normal pressure hydrocephalus, or subdural haematoma).
    4. Absence of a sudden, apoplectic onset, or of neurological signs of focal damage such as hemiparesis, sensory loss, visual field defects, and incoordination occurring early in the illness (although these phenomena may be superimposed later).

    In a certain proportion of cases, the features of Alzheimer's disease and vascular dementia may both be present. In such cases, double diagnosis (and coding) should be made. When the vascular dementia precedes the Alzheimer's disease, it may be impossible to diagnose the latter on clinical grounds.


    • primary degenerative dementia of the Alzheimer's type

    Differential Diagnosis

    Consider: a depressive disorder (F30-F39); delirium (F05); organic amnesic syndrome (F04); other primary dementias, such as in Pick's, Creuzfeldt-Jakob or Huntington's disease (F02.-); secondary dementias associated with a variety of physical diseases, toxic states, etc. (F02.8); mild, moderate or severe mental retardation (F70-F72).

    Dementia in Alzheimer's disease may coexist with vascular dementia (to be coded F00.2), as when cerebrovascular episodes (multi-infarct phenomena) are superimposed on a clinical picture and history suggesting Alzheimer's disease. Such episodes may result in sudden exacerbations of the manifestations of dementia. According to postmortem findings, both types may coexist in as many as 10-15% of all dementia cases.

    F00.0 Dementia In Alzheimer's Disease With Early Onset

    Dementia in Alzheimer's disease beginning before the age of 65. There is relatively rapid deterioration, with marked multiple disorders of the higher cortical functions. Aphasia, agraphia, alexia, and apraxia occur relatively early in the course of the dementia in most cases.

    Diagnostic Guidelines

    As for dementia, described above, with onset before the age of 65 years, and usually with rapid progression of symptoms. Family history of Alzheimer's disease is a contributory but not necessary factor for the diagnosis, as is a family history of Down's syndrome or of lymphoma.


    • Alzheimer's disease, type 2
    • presenile dementia, Alzheimer's type


    F00.1 Dementia In Alzheimer's Disease With Late Onset

    Dementia in Alzheimer's disease where the clinically observable onset is after the age of 65 years and usually in the late 70s or thereafter, with a slow progression, and usually with memory impairment as the principal feature.

    Diagnostic Guidelines

    As for dementia, described above, with attention to the presence or absence of features differentiating the disorder from the early-onset subtype (F00.0).


    • Alzheimer's disease, type 1
    • senile dementia, Alzheimer's type

    F00.2 Dementia In Alzheimer's Disease, Atypical Or Mixed Type

    Dementias that do not fit the descriptions and guidelines for either F00.0 or F00.1 should be classified here; mixed Alzheimer's and vascular dementias are also included here.

    ICD-10 copyright 1992 by World Health Organization.


    (National Institute of Neurological and Communicative Diseases and Stroke and distributed by the Long Island Alzheimers Foundation, 516 869-9627)

    1. Criteria for clinical diagnosis of probable Alzheimers disease include:

    • Dementia established by clinical examination and documented by Mini Mental (Folstein, Folstein, McHugh, 1975) Blessed Dementia Scale (Blessed, Tomlinson, Roth, 1968), or some other similar examination and confirmed by a neuropsychological tests
    • Deficits into more areas of cognition, progressive worsening of memory and other cognitive functions
    • No disturbance of consciousness
    • Onset between ages 40 in 90, most often after age 65
    • Absence of systemic disorders or other brain diseases that in a themselves could account for progressive deficits in memory and cognition

    2. Diagnosis of probable Alzheimers disease is supported by:

    • Progressive deterioration of specific cognitive functions, such as a language (Aphasia), motor skills (apraxia) and perception (agnosia)
    • Impaired activities of daily living and altered patterns of behavior
    • Family history of similar disorders, particularly if confirmed neuropathologically
    • Laboratory results of normal lumbar puncture as evaluated by standard techniques, normal pattern or nonspecific changes in EEG, such as increased slow-wave activity, and evidence of cerebral atrophy on CT with progression documented by serial observation

    3. Other clinical features consistent with diagnosis of probable Alzheimers disease, after exclusion of causes of dementia other than Alzheimers disease, include:

    • Plateaus in course of progression of illness
    • Associated symptoms of depression; insomnia; incontinence; delusions; illusions; hallucinations; catastrophic verbal, emotional, or physical outburst; sexual disorders; and weight loss
    • Other neurological and analyses in some patients, especially with more advanced disease and including motor signs, such as increased muscle tone, myoclonus, or gait disorder
    • Seizures in advanced disease
    • CT normal for age

    4. Features that make diagnosis of probable Alzheimers disease uncertain or unlikely include:

    • Sudden apoplectic onset
    • Focal neurological findings such as hemiparesis, sensory loss, visual field defects, and uncoordination early in the course of the illness
    • Seizures or gait disturbance at onset or very early in course of illness

    5. Clinical diagnosis of possible Alzheimers disease:

    • May be made on basis of dementia syndrome, in absence of other neurological, psychiatric, or systemic disorders sufficient to cause dementia and in the presence of variations in onset, in presentation, or in clinical course
    • May be made in presence of second systemic or brain disorder sufficient to produce dementia, which is not considered to be cause of dementia
    • Should be used in research studies when single, gradually progressive severe cognitive deficit is identified in absence of other identifiable cause

    6. Criteria for diagnosis of definite Alzheimers disease are:

    • Clinical criteria for probably Alzheimers disease
    • Histopathological evidence obtained from biopsy or at autopsy

    7. Classification of Alzheimers disease for research purposes should specify features that may differentiate subtypes of the disorders such as:

    • Familial occurrence
    • Onset before age of 65
    • Presence of Trisomy-21
    • Coexistence of other relevant conditions, such as Parkinson's disease

    Alzheimers (2000)

    Mild Stage

    • Memory loss becomes more noticeable
    • Concentrating and paying attention becomes harder, leading to difficulties in understanding written material, doing calculations, or making job-related decisions
    • Misplacing or losing valuable items
    • Momentary disorientation in familiar surroundings
    • Some changes in personality and judgment

    Moderate Stage

    • Memory loss about recent events and some details of personal lives
    • Inappropriate use of words
    • Difficulty in performing such tasks as planning meals and dressing
    • Increased disorientation
    • Agitation, anxiety, suspiciousness
    • Confusion between day and night
    • Sleep disturbances
    • Wandering off and not knowing how to return.
    • Failure to recognize friends and relatives

    Severe Stage

    • Memory loss nearly complete
    • Severe disorientation and confusion
    • Speech declines to a few intelligible words
    • Loss of physical functions like walking and sitting up
    • Loss of bladder and bowel control
    • Loss of appetite
    • Total dependence on caregiver



  • Definition

  • Chronic loss of previously acquired mental function

  • Causes of Dementia
    1. Alzheimer's Disease (Most common)
    2. AIDS or Human Immunodeficiency Virus (HIV)
    3. Multi-Infarct dementia
    4. Depression or pseudodementia
    5. Normal Pressure Hydrocephalus
    6. Mass lesions
    7. Drug toxicity or metabolic disturbance
      1. Anticholinergic Medications
    8. Pick's Disease
    9. Frontal lobe dementia
    10. Dementia with Lewy bodies
    11. Progressive supranuclear palsy
    12. Multiple-systems atrophy

    1. Risks Factors for Alzheimer's Disease
    2. Age
      1. Risk increases with age over 65 years
    3. Apo E4 Allele
      1. Confers 8% risk if two alleles
    4. Family History of Alzheimer's Disease
    5. FAD gene
    6. Female gender
    7. Low education
    8. Head Trauma
    9. Myocardial Infarction
    10. Combined CV factors in middle age (odds ratio 3.5)
      1. Hyperlipidemia
      2. Hypertension (increased systolic Blood Pressure)
      3. Kivipelto (2001) BMJ 322:1447-51

    1. Criteria
    2. Insidious, gradual onset (months) of deterioration
      1. Mild to severe fluctuations
      2. All higher cortical functions
    3. Long duration of symptoms
    4. Normal Level of Consciousness, but altered content
      1. See Signs below
    5. Vital signs typically normal

    1. Signs and symptoms
    2. Normal alertness, awareness, attentiveness
    3. No hallucinations or delusions
    4. Disorientation
    5. Memory Impairment (short much more than long term)
      1. New forgetfulness
      2. Difficult word finding
    6. Impaired Executive, Social, or cognitive function
      1. Driving difficulties or getting lost
      2. Neglect of self care and household chores
      3. Difficult money handling
      4. Work mistakes
      5. Judgement and Language impaired
    7. Behavior changes
      1. See Behavior Problems in Dementia
    8. Personality change
      1. Inappropriately friendly or even flirtatious
      2. Affect shallow or blunted or social withdrwal
      3. Frustration to explosive spells
    9. Psychiatric symptoms
      1. Suspiciousness or paranoia
      2. Withdrawal or apathy
      3. Abnormal beliefs or hallucinations

    1. Evaluation
    2. Mental Status Screening (rapid clinic screening)
    3. Mini-Mental Status Exam
      1. Standard decline 3 points per 6 months
      2. Error is +/- 3 points
    4. Addenbrooke's Cognitive Examination (ACE)
      1. Differentiate's Alzheimer's from other dementias
      2. Detect early dementia
    5. Psychometric Testing Indications
      1. Early dementia
      2. Depression
      3. Alcohol vs alzheimer's
      4. Unusual Dementias

    1. Dementia Diagnosis
    2. Amnesia (Wexler)
      1. Short Term Memory
      2. Long Term Memory
    3. One of the following (in addition to Amnesia Above)
      1. Aphasia (communication disorder)
      2. Apraxia (purposeful Movement Disorder)
      3. Agnosia (sensory interpretation deficit)
      4. Executive Function Disturbance (e.g. Serial 7's)

    1. Exascerbated by
    2. Illness
    3. Hospitalization
    4. Minor surgery
    5. Bereavement

    1. Associated Conditions:
    2. Gait Apraxia
    3. Disinhibited behavior
    4. Slurred speech if Vascular
    5. Anxiety, mood, and sleep disturbance
    6. Delusions and visual hallucinations
    7. Speech rambling, irrelevant, and incoherent
    8. Personality change

    1. Labs and Diagnostic Testing
    2. Goals: Rule out reversible cause (Delirium Causes)
    3. Standard Evaluation
      1. Urinalysis
      2. Complete Blood Count (CBC)
      3. Serum Vitamin B12 Level
      4. Metabolic screen (chem 18, SMA 19)
        1. Serum Electrolytes with Magnesium
        2. Liver Function Tests
      5. Thyroid Stimulating Hormone (TSH)
      6. Syphilis Serology (VDRL or RPR)
      7. CT Head or MRI Head
    4. Possible Evaluation
      1. Erythrocyte Sedimentation Rate (ESR)
      2. Chest XRay
    5. Evaluation only as indicated
      1. Arterial Blood Gas (ABG)
      2. Medication Levels
      3. Electrocardiogram (ECG)
      4. Electroencephalogram (EEG)
        1. Seizure disorder
        2. Creutzfeldt-Jakob Disease
      5. Lyme Titer
      6. Lumbar Puncture for rapidly progressive dementia
        1. Systemic signs and symptoms
        2. Atypical presentation
        3. Cancer
        4. Infectious disease
        5. Hydrocephalus
      7. Apolipoprotein E
      8. Heavy metal screening
      9. Ceruplasmin for Wilson' Disease
      10. Arylsulfatase for metachromatic leukodystrophy
      11. Serum Protein Electrophoresis for Multiple Myeloma
      12. Human Immunodeficiency Virus (HIV)
      13. Connective Tissue Disease
        1. Antinuclear Antibody (ANA)
        2. C3 Complement
        3. C4 Complement
        4. Anti-DS DNA
      14. Urine Toxicologic screen
      15. Urine porphobilinogens

    1. Special Tests (Research use only currently)
    2. Cerebrospinal Fluid for Alzheimer's specific proteins
      1. High tau
      2. Low Beta-Amyloid
    3. MRI Head
      1. Atrophy of hippocampus and temporal lobe
    4. Functional imaging
      1. SPECT scan
      2. PET scan
      3. Functional Head MRI

    1. Course
    2. Cases due to reversible cause: 20%
    3. High index of suspicion for reversibility in elderly

    1. Management
    2. See Dementia Management

    1. Neurology Consultation Indications
    2. Rapidly progressive dementia
    3. Dementia in a young patient
    4. Severe behavior psychiatric abnormalities
    5. Red Flags for uncommon dementia
      1. Significant personality change
      2. Extrapyramidal signs
      3. Rapid progression
      4. Gaze palsy
      5. Urinary Incontinence
      6. Gait abnormality

    1. Resources
    2. See Dementia Resources

    1. References
    2. Daly (1999) J Am Board Fam Pract 12:375-85
    3. Santacruz (2001) Am Fam Physician 63:703-18
    4. (1994) Neurology 44:2203-6
  • Alzheimer's Disease (AD), a term coined by Alois Alzheimer in 1907.