Table 1. Early-onset forms of adult neurodegenerative disorders.
| Disorder | Pathogenesis | Age of Onset | Disease Duration | Clinical Features in addition to Cognitive Dysfunction | Specific Diagnostic Studies with Suggested Order of Testing | Interventions in addition to Supportive Care |
|---|---|---|---|---|---|---|
| Alzheimer dementia14-20 | Sporadic AD mutation of APP, PSEN1, or PSEN2 | 40-50 years | 8-10 years | Behavioral features (agitation, withdrawal, hallucinations), motor symptoms, myoclonus | CT or MRI (cerebral cortical atrophy); FDG-PET (cerebral hypometabolism posterior> anterior); CSF (low Aβ 42 and high tau); genetic testing | Cholinesterase inhibitor (donepezil, rivastigmine, galantamine), NMDA receptor antagonist (memantine) |
| Vascular dementia | ||||||
| CADASIL21,23,25,26,28 | AD mutation of NOTCH3 on Chr19 | 30-60 years | Variable | Psychiatric features (mood disturbance, apathy), migraine with aura, cerebrovascular disease, seizures | MRI (begin asT2 hyperintensities in temporal lobe/external capsule and subcortical infarcts, progress to diffuse white matter changes); EEG (epileptiform discharges over affected areas); skin biopsy (granular osmophilic material in media of arterioles on EM); genetic testing | Antiplatelet therapy, control hypertension and hypecholesterolemia |
| Cerebral amyloid angiopathy22,24,27,29,30 | Sporadic AD mutations in the APP, CST3, or ITM2B genes | 45-70 years | Variable | Lobar intracerebral hemorrhage, headache, focal neurological deficits | MRI (gradient echo sequence with multiple microbleeds in cortex; routine sequences may reveal lacunar infarctions or confluent white matter changes); genetic testing | Lipid lowering agents |
| Behcet's disease187,188 | Autoimmune (triggered by infection) associated with HLA-B51 | 20-40 years | Variable | Oral/urogenital/cutaneous lesions, ocular disease, vascular disease, arthritis, seizures, psychiatric symptoms and personality change | MRI (lesions of corticospinal tract, brainstem, periventricular white matter, spinal cord, basal ganglia); CSF (elevated opening pressure, increased protein or pleocytosis) | Glucocorticoids, immunosuppressant medications |
| Frontotemporal dementia31,33-36 | Sporadic AD mutation of MAPT or GRN on Chr17 or hexanucleotide repeat C9ORF72 | 35-87 years | 3-12 years | Behavior and personality change, aphasia, dysarthria, dysphagia, associated parkinsonism or motor neuron disease | CT or MRI (regionally specific frontal and temporal atrophy); FDG-PET (anterior> posterior hypometabolism); genetic testing | SSRI |
| Alpha synuclein pathology | ||||||
| Lewy body dementia37,38,42 | Sporadic Rare mutations in SNCA, SNCB | 50-83 years | 10-15 years | Fluctuating alertness, visual hallucinations, parkinsonism, REM sleep behavior disorder | MRI (normal for age or mild atrophy of cortex and putamen); polysomnography for loss of muscle atonia in REM sleep | Cholinesterase inhibitor, SSRI, +/- low dose atypical neuroleptic, +/-levodopa |
| Multiple system atrophy37,39-41,43 | Sporadic Rare associations with SNCA gene | 54-60 years | 6-10 years | Parkinsonism with anterocollis, autonomic failure, ataxia, pyramidal signs, REM sleep behavior disorder, nocturnal stridor | MRI (brainstem “hot cross bun” sign or hypointensity of extreme capsule); polysomnography for loss of muscle atonia in REM sleep; autonomic testing; genetic testing | Poor response to levodopa, florinef, or midodrine for orthostatic hypotension |
| Huntington's disease44-48 | AD mutation of CAG repeats in HTT gene on Chr4 | 35-44 years | 15-18 years | Chorea, prominent behavioral features and personality change | MRI (atrophy of caudate and putamen); genetic testing | Typical or atypical neuroleptics, tetrabenazine |
| Creutzfeldt Jakob disease49-52 | Sporadic (sCJD) Acquired (vCJD) Iatrogenic (iCJD) Genetic (gCJD) AD mutation of PRNP on Chr20 |
30-50 years | 2 months to 2 years | Ataxia, myoclonus, personality change | MRI (DWI and FLAIR sequences with cortical ribboning, hyperintense basal ganglia and thalamus); CSF (incr 14-3-3 protein); EEG (triphasic or sharp wave bursts every 0.5 to 2 sec); genetic testing | |
| Fahr's disease55-59 | Familial but no gene identified | 30-50 years | Variable | Change in personality and behavior or psychosis, motor speech disorder, ataxia, movement disorder, seizures | CT (Ca deposits in bilateral basal ganglia or cerebellum); MRI (calcified areas of basal ganglia and cerebellum hypointense on T2 and hyperintense on T1 sequences); blood tests (normal Ca, P, Mg, alkaline phosphatase, calcitonin, PTH) | |
| Chronic traumatic encephalopathy53,54 | Repetitive injury to brain (e.g. professional athletes, blast injury) | Variable | Variable | Depression, apathy, poor impulse control, multi-domain cognitive decline, variable parkinsonism | MRI (generalized and medial temporal lobe atrophy or ventriculomegaly) |
Abbreviations: CSF = cerebrospinal fluid
CT = computed tomography
MRI = magnetic resonance imaging
FDG-PET = fluorodeoxyglucose positron emission tomography
SPECT = single-photon emission computed tomography
DWI = diffusion weighted imaging
EM = electron micrography
EEG = electroencephalography
SSRI = selective serotonin reuptake inhibitor
REM = rapid eye movement
AD = autosomal dominant tomography
Chr = chromosome
HLA = human leukocyte antigen
PTH = parathyroid hormone