ABSTRACT
Apolipoprotein E (ApoE) status and gender are risk factors for the development of Alzheimer's disease. Alzheimer's disease is more prevalent in female relative to male carriers of the ApoE epsilon 4 gene. We examined cortical sensory (P50, N100) and cognitive (P300) potentials in an auditory target detection task in females as a function of ApoE genotype (ApoE epsilon 4 carriers, ApoE epsilon 4 non-carriers) to define the incidence of abnormalities prior to the clinical expression of cognitive impairments. Both neuropsychological test scores and sensory cortical potentials did not differ between the two ApoE groups. In contrast, cognitive P300 potentials were significantly decreased in amplitude and delayed in latency for ApoE epsilon 4 carriers compared to non-carriers. Four out of the 10 ApoE epsilon 4 carriers had abnormally (>2S.D.) delayed P300 latency compared to one out of 20 non-carriers. Abnormal cognitive processes reflected by P300 latency delays are expressed at significantly higher incidence in normal older females who are carriers of the epsilon 4 allele than in non-carriers of this allele.
Subject(s)
Apolipoprotein E4/genetics , Auditory Cortex/physiology , Auditory Perception/genetics , Auditory Perceptual Disorders/genetics , Aged , Alzheimer Disease/genetics , Evoked Potentials/genetics , Evoked Potentials, Auditory/genetics , Evoked Potentials, Auditory/physiology , Female , Humans , Middle Aged , Neuropsychological TestsABSTRACT
Mild cognitive impairment (MCI) patients have a high risk of converting to Alzheimer's disease. The most common diagnostic subtypes of MCI have an episodic memory disorder (amnestic MCI) occurring either alone [single domain (SD)] or with other cognitive impairments [multiple domain (MD)]. Previous studies report increased amplitudes of auditory cortical potentials in MCI, but their relationships to MCI subtypes and clinical outcomes were not defined. We studied subjects with amnestic MCI (n = 41: 28 SD, 13 MD), Alzheimer's disease (n = 14), and both younger (n = 22) and age-matched older controls (n = 44). Baseline auditory sensory (P50, N100) and cognitive potentials (P300) were recorded during an auditory discrimination task. MCI patients were followed for up to 5 years, and outcomes were classified as (i) continued diagnosis of MCI (MCI-stable, n = 16), (ii) probable Alzheimer's disease (MCI-convert, n = 18), or other outcomes (n = 7). Auditory potentials were analysed as a function of MCI diagnosis and outcomes, and compared with young, older controls, and mild Alzheimer's disease subjects. P50 amplitude increased with normal ageing, and had additional increases in MCI as a function of both initial diagnosis (MD > than SD) and outcome (MCI-convert > MCI-stable). P300 latency increased with normal ageing, and had additional increases in MCI but did not differ among outcomes. We conclude that auditory cortical sensory potentials differ among amnestic MCI subtypes and outcomes occurring up to 5 years later.
Subject(s)
Alzheimer Disease/physiopathology , Auditory Cortex/physiopathology , Memory Disorders/physiopathology , Aged , Aging/physiology , Alzheimer Disease/psychology , Evoked Potentials/physiology , Evoked Potentials, Auditory/physiology , Female , Humans , Language Disorders/physiopathology , Language Disorders/psychology , Male , Memory/physiology , Memory Disorders/psychology , Neuropsychological Tests , Prognosis , Reaction Time , Sex FactorsABSTRACT
Amnestic mild cognitive impairment (MCI) is an isolated episodic memory disorder that has a high likelihood of progressing to Alzheimer's disease. Auditory sensory cortical responses (P50, N100) have been shown to be increased in amplitude in MCI compared to older controls. We tested whether (1) cortical potentials to other sensory modalities (somatosensory and visual) were also affected in MCI and (2) cholinesterase inhibitors (ChEIs), one of the therapies used in this disorder, modulated sensory cortical potentials in MCI. Somatosensory cortical potentials to median nerve stimulation and visual cortical potentials to reversing checkerboard stimulation were recorded from 15 older controls and 15 amnestic MCI subjects (single domain). Results were analyzed as a function of diagnosis (Control, MCI) and ChEIs treatment (Treated MCI, Untreated MCI). Somatosensory and visual potentials did not differ significantly in amplitude in MCI subjects compared to controls. When ChEIs use was considered, somatosensory potentials (N20, P50) but not visual potentials (N70, P100, N150) were of larger amplitude in untreated MCI subjects compared to treated MCI subjects. Three individual MCI subjects showed increased N20 amplitude while off ChEIs compared to while on ChEIs. An enhancement of N20 somatosensory cortical activity occurs in amnestic single-domain MCI and is sensitive to modulation by ChEIs.
