What can imaging tell us about cognitive impairment and dementia?

Table 1 Causes of dementia and dementia syndromes

Types of dementia
Primary dementias
Alzheimer’s disease
Late-onset Alzheimer’s disease - most common form 60%-70% of all dementias
Early-onset Alzheimer’s disease - under 65 yr of age, chromosome 14 implicated, Down’s syndrome
Familial AD - inheritable form present in at least 2 generations within families
Dementia with Lewy bodies
Frontotemporal dementia
Mixed dementia - more than one form of pathology for, e.g., Lewy bodies with Alzheimer’s disease
Less common forms
Parkinson’s disease
Progressive supranuclear palsy
Huntington’s disease
Secondary dementias
Vascular/multi infarct dementia
Vascular with Alzheimer’s disease
Creutzfeldt-Jakob disease
Intracranial mass lesions
Normal pressure hydrocephalus
Subdural haematomas
Trauma
Infections - primarily human immunodeficiency virus
Alcohol
Other documented causes
Vitamin deficiencies - vitamins E, B and folic acid are implicated
Medications
Other causes like depression

Table 2 Summary

Dementia	Pathological feature	Structural imaging CT/MRI	Molecular imaging (non-specific)	Molecular imaging (specific)	Research
Alzheimer’s disease	Primary neurodegenerative, extracellular amyloid plaques (Aβ42), intracellular tau aggregates[13], Autosomal dominant early onset inherited form - presenelins are also implicated[22]	Hippocampal-medial temporal lobe (CA2 and CA3 hippocampal subregions are more affected), posterior cingulate gyrus and postero-medial parietal lobe atrophy on MRI and CT	SPECT1- ↓perfusion FDG PET2- ↓glucose uptake in medial temporal lobe and hippocampi[39-41]	11C PIB, Florbetapir3 uptake in amyloid plaques[42]	Tau specific ligands -PET, MRI-BOLD, fMRI-↓connectivity in DMN, MR perfusion[38], MR spectroscopy, DTI -↓medial temporal lobe and precuneus[34], VBM
LBD	Intracellular Lewy bodies-aggregates of α-synuclein particles in pre-synaptic terminals Overlaps with Parkinson’s disease	Atrophy in inferior frontal lobe, visual cortex, insula, hypothalamus, midbrain, caudate, putamen and anterior hippocampi (CA1 subregion)[86]	SPECT -↓in putamen and caudate, visual cortex[88,89] FDG PET -↓in visual cortices[88-90]	FP-CIT-↓uptake in putamen and caudate[79] Cholinergic PET/SPECT- ↓in medial occipital lobe[95] 123I MIBG-↓cardiac uptake[96]	Diffusion weighted MR-DTI, ↓ in visual association cortex and posterior putamen MRS, fMRI ASL-MR
FTD	Various proteins including tauopathies, TDP43, FUS- clinically can overlap with PSP, MSA, MND[100,101]	Variable-predominantly anterior frontal, temporal and insular atrophy[102,103]	FDG PET and SPECT-↓anterior, frontal and temporal uptake[107]	-	fMRI, DTI-↓ in WM of affected regions[104] fMRI-↓"salient" network’ but ↑DMN connectivity on resting fMRI- unlike AD[105,106]
Vascular dementia	Small and large vessel disease - vascular risk factors like HT, smoking and DM implicated[61] CADASIL- hereditary form	CT-cortical infarct, macrohaemorrhage, frontal subcortical and periventricular WMH, lacunes[62-67] MRI-CT features as above and PVS, CMB	FDG PET and rCBF SPECT-↓ frontal and periventricular regions	-	-
CJD sCJD vCJD	Prion protein - sources include food, tissues, genetic variation	MRI-↑signal on T2W and DWI in the caudate and cortex ("cortical ribboning") MRI-↑ on T2W and DWI in the pulvinar of thalami
Autoimmune encephalitis related dementia	Previously limbic encephalitis -neuron specific CSF autoantibodies Paraneoplastic syndrome	MRI-↑ signal on T2W and FLAIR in the mesial temporal lobe	FDG PET -↑ uptake in the medial temporal lobe Whole body PET to identify underlying primary malignancy[110]

¹SPECT-radiotracer is ^99mTc hexamethylpropylene amine oxime;

²FDG PET-radiotracer is ¹⁸F-FDG;

³Recently approved by FDA for clinical use in specific cases, primarily to exclude Alzheimer’s disease.↑: Increased; ↓: Decreased; Aβ42: Beta amyloid protein with 42 amino acids; CA1, CA2, CA3: Subfields of hippocampus; ASL- MR: Arterial spin labelling MR; BOLD: Blood oxygenation level dependent; CADASIL: Congenital autosomal dominant arteriopathy with subcortical infarcts and leukoencephalopathy; CMB: Cerebral microbleeds; CSF: Cerebrospinal fluid; DM: Diabetes mellitus; DTI: Diffusion tensor imaging; FDG: Fludeoxyglucose; FLAIR: Fluid-attenuated inversion–recovery; fMRI: Functional MRI; DMN: Default mode network; FP-CIT: Dopaminergic presynaptic ligand iodine-123-b-carbo-methoxy-3 b-(4-iodophenyltropane) fluoropropyl; FUS: Fused in sarcoma protein; HT: Hypertension; LBD: Lewy body dementia; MSA: Multisystem atrophy; MND: Motor neuron disease; MRS: MR spectroscopy; PET: Positron emission tomography; PIB: Pittsburgh compound B; PSP: Progressive supranuclear palsy; PVS: Perivascular spaces; rCBF SPECT: Regional cerebral blood flow SPECT; sCJD: Sporadic form of Creutzfeldt–Jacob disease; vCJD: Variant form of Creutzfeldt–Jacob disease; SPECT: Single photon emission computed tomography; T2W: T2 weighted; TDP43: Transactive DNA-binding protein; VBM: Voxel-based morphometry; WMH: White matter hyperintensities.